bibliography.bib

@article{Anderson1990,
abstract = {Phospholipase C gamma 1 (PLC gamma 1) and p21ras guanosine triphosphatase (GTPase) activating protein (GAP) bind to and are phosphorylated by activated growth factor receptors. Both PLC gamma 1 and GAP contain two adjacent copies of the noncatalytic Src homology 2 (SH2) domain. The SH2 domains of PLC gamma 1 synthesized individually in bacteria formed high affinity complexes with the epidermal growth factor (EGF)- or platelet derived growth factor (PDGF)-receptors in cell lysates, and bound synergistically to activated receptors when expressed together as one bacterial protein. In vitro complex formation was dependent on prior growth factor stimulation and was competed by intracellular PLC gamma 1. Similar results were obtained for binding of GAP SH2 domains to the PDGF-receptor. The isolated SH2 domains of other signaling proteins, such as p60src and Crk, also bound activated PDGF-receptors in vitro. SH2 domains, therefore, provide a common mechanism by which enzymatically diverse regulatory proteins can physically associate with the same activated receptors and thereby couple growth factor stimulation to intracellular signal transduction pathways.},
author = {Anderson, D and Koch, C A and Grey, L and Ellis, C and Moran, M F and Pawson, T},
doi = {10.1126/science.2173144},
journal = {Science},
month = {nov},
number = {4983},
pages = {979 LP  -- 982},
title = {{Binding of SH2 domains of phospholipase C gamma 1, GAP, and Src to activated growth factor receptors}},
url = {http://science.sciencemag.org/content/250/4983/979.abstract},
volume = {250},
year = {1990}
}
@article{Assenov2008,
abstract = {Rapidly increasing amounts of molecular interaction data are being produced by various experimental techniques and computational prediction methods. In order to gain insight into the organization and structure of the resultant large complex networks formed by the interacting molecules, we have developed the versatile Cytoscape plugin NetworkAnalyzer. It computes and displays a comprehensive set of topological parameters, which includes the number of nodes, edges, and connected components, the network diameter, radius, density, centralization, heterogeneity, and clustering coefficient, the characteristic path length, and the distributions of node degrees, neighborhood connectivities, average clustering coefficients, and shortest path lengths. NetworkAnalyzer can be applied to both directed and undirected networks and also contains extra functionality to construct the intersection or union of two networks. It is an interactive and highly customizable application that requires no expert knowledge in graph theory from the user. AVAILABILITY: NetworkAnalyzer can be downloaded via the Cytoscape web site: http://www.cytoscape.org},
author = {Assenov, Yassen and Ram{\'{i}}rez, Fidel and Schelhorn, S. E.Sven Eric and Lengauer, Thomas and Albrecht, Mario},
doi = {10.1093/bioinformatics/btm554},
file = {:Users/ozlem/Dropbox/papers/Biological Networks/btm554.pdf:pdf},
isbn = {1367-4811 (Electronic)$\backslash$r1367-4803 (Linking)},
issn = {13674803},
journal = {Bioinformatics},
pmid = {18006545},
title = {{Computing topological parameters of biological networks}},
year = {2008}
}
@article{Davis2015,
abstract = {Directly modulating the activity of genome-editing proteins has the potential to increase their specificity by reducing activity following target locus modification. We developed Cas9 nucleases that are activated by the presence of a cell-permeable small molecule by inserting an evolved 4-hydroxytamoxifen-responsive intein at specific positions in Cas9. In human cells, conditionally active Cas9s modify target genomic sites with up to 25-fold higher specificity than wild-type Cas9.},
archivePrefix = {arXiv},
arxivId = {arXiv:1011.1669v3},
author = {Davis, Kevin M and Pattanayak, Vikram and Thompson, David B and Zuris, John A and Liu, David R},
doi = {10.1038/nchembio.1793},
eprint = {arXiv:1011.1669v3},
isbn = {1552-4469 (Electronic)$\backslash$r1552-4450 (Linking)},
issn = {1552-4450},
journal = {Nature Chemical Biology},
number = {5},
pages = {316--318},
pmid = {25848930},
title = {{Small molecule–triggered Cas9 protein with improved genome-editing specificity}},
url = {http://www.nature.com/doifinder/10.1038/nchembio.1793},
volume = {11},
year = {2015}
}
@article{Wang2012,
abstract = {Mathematical modeling of biological processes provides deep insights into complex cellular systems. While quantitative and continuous models such as differential equations have been widely used, their use is obstructed in systems wherein the knowledge of mechanistic details and kinetic parameters is scarce. On the other hand, a wealth of molecular level qualitative data on individual components and interactions can be obtained from the experimental literature and high-throughput technologies, making qualitative approaches such as Boolean network modeling extremely useful. In this paper, we build on our research to provide a methodology overview of Boolean modeling in systems biology, including Boolean dynamic modeling of cellular networks, attractor analysis of Boolean dynamic models, as well as inferring biological regulatory mechanisms from high-throughput data using Boolean models. We finally demonstrate how Boolean models can be applied to perform the structural analysis of cellular networks. This overview aims to acquaint life science researchers with the basic steps of Boolean modeling and its applications in several areas of systems biology.},
author = {Wang, Rui Sheng and Saadatpour, Assieh and Albert, R{\'{e}}ka},
doi = {10.1088/1478-3975/9/5/055001},
file = {:Users/ozlem/Desktop/Wang{\_}2012{\_}Phys.{\_}Biol.{\_}9{\_}055001.pdf:pdf},
isbn = {1478-3967},
issn = {14783967},
journal = {Physical Biology},
number = {5},
pmid = {23011283},
title = {{Boolean modeling in systems biology: An overview of methodology and applications}},
volume = {9},
year = {2012}
}
@article{Jacinto2004,
abstract = {The target of rapamycin (TOR) is a highly conserved protein kinase and a central controller of cell growth. In budding yeast, TOR is found in structurally and functionally distinct protein complexes: TORC1 and TORC2. A mammalian counterpart of TORC1 (mTORC1) has been described, but it is not known whether TORC2 is conserved in mammals. Here, we report that a mammalian counterpart of TORC2 (mTORC2) also exists. mTORC2 contains mTOR, mLST8 and mAVO3, but not raptor. Like yeast TORC2, mTORC2 is rapamycin insensitive and seems to function upstream of Rho GTPases to regulate the actin cytoskeleton. mTORC2 is not upstream of the mTORC1 effector S6K. Thus, two distinct TOR complexes constitute a primordial signalling network conserved in eukaryotic evolution to control the fundamental process of cell growth.},
author = {Jacinto, Estela and Loewith, Robbie and Schmidt, Anja and Lin, Shuo and R{\"{u}}egg, Markus A. and Hall, Alan and Hall, Michael N.},
doi = {10.1038/ncb1183},
isbn = {1465-7392 (Print)$\backslash$r1465-7392 (Linking)},
issn = {14657392},
journal = {Nature Cell Biology},
pmid = {15467718},
title = {{Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive}},
year = {2004}
}
@article{Flandin2009,
abstract = {Event-related skin conductance responses (SCRs) are traditionally analysed by comparing the amplitude of individual peaks against a pre-stimulus baseline. Many experimental manipulations in cognitive neuroscience dictate paradigms with short inter trial intervals, precluding accurate baseline estimation for SCR measurements. Here, we present a novel and general approach to SCR analysis, derived from methods used in neuroimaging that estimate responses using a linear convolution model. In effect, the method obviates peak-scoring and makes use of the full SCR. We demonstrate, across three experiments, that the method has face validity in analysing reactions to a loud white noise and emotional pictures, can be generalised to paradigms where the shape of the response function is unknown and can account for parametric trial-by-trial effects. We suggest our approach provides greater flexibility in analysing SCRs than existing methods.},
author = {Flandin, Guillaume and Flandin, Guillaume and Friston, Karl J and Friston, Karl J and Dolan, Raymond J and Dolan, Raymond J},
doi = {10.1016/j.jneumeth.2008.10.036},
journal = {Journal of Neuroscience Methods},
keywords = {convolution,deconvolution,eda,electrodermal activity,galvanic skin response,general linear model,gsr,linear time invariant filter,scr,skin conductance},
number = {2},
pages = {224--234},
title = {{Journal of Neuroscience Methods}},
volume = {184},
year = {2009}
}
@article{Baryshnikova2010,
abstract = {Global quantitative analysis of genetic interactions is a powerful approach for deciphering the roles of genes and mapping functional relationships among pathways. Using colony size as a proxy for fitness, we developed a method for measuring fitness-based genetic interactions from high-density arrays of yeast double mutants generated by synthetic genetic array (SGA) analysis. We identified several experimental sources of systematic variation and developed normalization strategies to obtain accurate single- and double-mutant fitness measurements, which rival the accuracy of other high-resolution studies. We applied the SGA score to examine the relationship between physical and genetic interaction networks, and we found that positive genetic interactions connect across functionally distinct protein complexes revealing a network of genetic suppression among loss-of-function alleles.},
author = {Baryshnikova, Anastasia and Costanzo, Michael and Kim, Yungil and Ding, Huiming and Koh, Judice and Toufighi, Kiana and Youn, Ji Young and Ou, Jiongwen and {San Luis}, Bryan Joseph and Bandyopadhyay, Sunayan and Hibbs, Matthew and Hess, David and Gingras, Anne Claude and Bader, Gary D. and Troyanskaya, Olga G. and Brown, Grant W. and Andrews, Brenda and Boone, Charles and Myers, Chad L.},
doi = {10.1038/nmeth.1534},
isbn = {1548-7105 (Electronic) 1548-7091 (Linking)},
issn = {15487091},
journal = {Nature Methods},
number = {12},
pages = {1017--1024},
pmid = {21076421},
title = {{Quantitative analysis of fitness and genetic interactions in yeast on a genome scale}},
volume = {7},
year = {2010}
}
@article{Karlsson2011,
abstract = {Abundant microorganisms that inhabit the human intestine are implicated in health and disease. The gut microbiome has been studied with metagenomic tools, and over 3 million genes have been discovered, constituting a 'parts list' of this ecosystem; further understanding requires studies of the interacting parts. Mouse models have provided a glimpse into the microbiota and host interactions at metabolic and immunologic levels; however, to provide more insight, there is a need to generate mathematical models that can reveal genotype-phenotype relationships and provide scaffolds for integrated analyses. To this end, we propose the use of genome-scale metabolic models that have successfully been used in studying interactions between human hosts and microbes, as well as microbes in isolation and in communities. {\textcopyright} 2011 Elsevier Ltd.},
author = {Karlsson, Fredrik H. and Nookaew, Intawat and Petranovic, Dina and Nielsen, Jens},
doi = {10.1016/j.tibtech.2011.01.009},
isbn = {1879-3096 (Electronic)$\backslash$r0167-7799 (Linking)},
issn = {01677799},
journal = {Trends in Biotechnology},
pmid = {21392838},
title = {{Prospects for systems biology and modeling of the gut microbiome}},
year = {2011}
}
@article{Okazaki1995,
abstract = {The c-mos proto-oncogene product, Mos, is a serine/threonine kinase that can activate ERK1 and 2 mitogen-activated protein (MAP) kinases by direct phosphorylation of MAPK/ERK kinase (MEK). ERK activation is essential for oncogenic transformation of NIH 3T3 cells by Mos. In this study, we examined how mitogenic and oncogenic signalling from the Mos/MEK/ERK pathway reaches the nucleus to activate downstream target genes. We show that c-Fos (the c-fos protooncogene product), which is an intrinsically unstable nuclear protein, is metabolically highly stabilized, and greatly enhances the transforming efficiency of NIH 3T3 cells, by Mos. This stabilization of c-Fos required Mos-induced phosphorylation of its C-terminal region on Ser362 and Ser374, and double replacements of these serines with acidic (Asp) residues markedly increased the stability and transforming efficiency of c-Fos even in the absence of Mos. Moreover, activation of the ERK pathway was necessary and sufficient for the c-Fos phosphorylation and stabilization by Mos. These results indicate that c-Fos undergoes stabilization, and mediates at least partly the oncogenic signalling, by the Mos/MEK/ERK pathway. The present findings also suggest that, in general, the ERK pathway may regulate the cell fate and function by affecting the metabolic stability of c-Fos.},
author = {Okazaki, Kenji and Sagata, Noriyuki},
doi = {10.1038/sj.emboj.7601127},
isbn = {0261-4189 (Print)$\backslash$r0261-4189 (Linking)},
issn = {0261-4189},
journal = {The EMBO journal},
keywords = {3T3 Cells,Amino Acid Sequence,Animals,Calcium-Calmodulin-Dependent Protein Kinases,Calcium-Calmodulin-Dependent Protein Kinases: meta,Cell Nucleus,Cell Nucleus: metabolism,Cell Transformation,Cloning,Immunoblotting,Mice,Mitogen-Activated Protein Kinases,Mitogen-Activated Protein Kinases: metabolism,Molecular,Molecular Sequence Data,Mutation,Neoplastic,Nerve Tissue Proteins,Nerve Tissue Proteins: metabolism,Phosphorylation,Precipitin Tests,Proto-Oncogene Proteins c-fos,Proto-Oncogene Proteins c-fos: genetics,Proto-Oncogene Proteins c-fos: metabolism,Proto-Oncogene Proteins c-mos,Proto-Oncogene Proteins c-mos: metabolism,Recombinant Proteins,Recombinant Proteins: metabolism,Serine,Serine: metabolism,Signal Transduction,Transfection},
pmid = {7588633},
title = {{The Mos/MAP kinase pathway stabilizes c-Fos by phosphorylation and augments its transforming activity in NIH 3T3 cells.}},
year = {1995}
}
@article{Pinilla-Macua2017,
abstract = {{\textless}p{\textgreater}Despite a well-established role for the epidermal growth factor receptor (EGFR) in tumorigenesis, EGFR activities and endocytosis in tumors in vivo have not been studied. We labeled endogenous EGFR with GFP by genome-editing of human oral squamous cell carcinoma cells, which were used to examine EGFR-GFP behavior in mouse tumor xenografts in vivo. Intravital multiphoton imaging, confocal imaging of cryosections and biochemical analysis revealed that localization and trafficking patterns, as well as levels of phosphorylation and ubiquitylation of EGFR in tumors in vivo closely resemble patterns and levels observed in the same cells treated with 20–200 pM EGF in vitro. Consistent with the prediction of low ligand concentrations in tumors, EGFR endocytosis was kinase-dependent and blocked by inhibitors of clathrin-mediated internalization; and EGFR activity was insensitive to Cbl overexpression. Collectively, our data suggest that a small pool of active EGFRs is sufficient to drive tumorigenesis by signaling primarily through the Ras-MAPK pathway.{\textless}/p{\textgreater}},
author = {Pinilla-Macua, Itziar and Grassart, Alexandre and Duvvuri, Umamaheswar and Watkins, Simon C. and Sorkin, Alexander},
doi = {10.7554/eLife.31993},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Pinilla-Macua et al. - 2017 - EGF receptor signaling, phosphorylation, ubiquitylation and endocytosis in tumors in vivo.pdf:pdf},
issn = {2050084X},
journal = {eLife},
pages = {1--25},
pmid = {29268862},
title = {{EGF receptor signaling, phosphorylation, ubiquitylation and endocytosis in tumors in vivo}},
volume = {6},
year = {2017}
}
@article{Kanehisa2008,
abstract = {KEGG (http://www.genome.jp/kegg/) is a database of biological systems that integrates genomic, chemical and systemic functional information. KEGG provides a reference knowledge base for linking genomes to life through the process of PATHWAY mapping, which is to map, for example, a genomic or transcriptomic content of genes to KEGG reference pathways to infer systemic behaviors of the cell or the organism. In addition, KEGG provides a reference knowledge base for linking genomes to the environment, such as for the analysis of drug-target relationships, through the process of BRITE mapping. KEGG BRITE is an ontology database representing functional hierarchies of various biological objects, including molecules, cells, organisms, diseases and drugs, as well as relationships among them. KEGG PATHWAY is now supplemented with a new global map of metabolic pathways, which is essentially a combined map of about 120 existing pathway maps. In addition, smaller pathway modules are defined and stored in KEGG MODULE that also contains other functional units and complexes. The KEGG resource is being expanded to suit the needs for practical applications. KEGG DRUG contains all approved drugs in the US and Japan, and KEGG DISEASE is a new database linking disease genes, pathways, drugs and diagnostic markers.},
author = {Kanehisa, Minoru and Araki, Michihiro and Goto, Susumu and Hattori, Masahiro and Hirakawa, Mika and Itoh, Masumi and Katayama, Toshiaki and Kawashima, Shuichi and Okuda, Shujiro and Tokimatsu, Toshiaki and Yamanishi, Yoshihiro},
doi = {10.1093/nar/gkm882},
isbn = {1362-4962 (Electronic)$\backslash$r0305-1048 (Linking)},
issn = {03051048},
journal = {Nucleic Acids Research},
pmid = {18077471},
title = {{KEGG for linking genomes to life and the environment}},
year = {2008}
}
@article{Jansson2010,
abstract = {Background: We have examined the phylogenetic pattern among eukaryotes of homologues of the E. coli 7,8-dihydro-8-oxoguanine (8-oxo-G) repair enzymes MutY, MutM, and MutT. Results: These DNA repair enzymes are present in all large phylogenetic groups, with MutM homologues being the most universally conserved. All chordates and echinoderms were found to possess all three 8-oxo-G repair components. Likewise, the red and green algae examined have all three repair enzymes, while all land-living plants have MutY and MutM homologues, but lack MutT. However, for some phyla, e.g. protostomes, a more patchy distribution was found. Nematodes provide a striking example, where Caenorhabditis is the only identified example of an organism group having none of the three repair enzymes, while the genome of another nematode, Trichinella spiralis, instead encodes all three. The most complex distribution exists in fungi, where many different patterns of retention or loss of the three repair components are found. In addition, we found sequence insertions near or within the catalytic sites of MutY, MutM, and MutT to be present in some subgroups of Ascomycetes. Conclusion: The 8-oxo-G repair enzymes are ancient in origin, and loss of individual 8-oxo-G repair components at several distinct points in evolution appears to be the most likely explanation for the phylogenetic pattern among eukaryotes.},
author = {Jansson, Kristina and Blomberg, Anders and Sunnerhagen, Per and {Alm Rosenblad}, Magnus},
doi = {10.1186/2041-9414-1-12},
issn = {20419414},
journal = {Genome Integrity},
pmid = {20809962},
title = {{Evolutionary loss of 8-oxo-G repair components among eukaryotes}},
volume = {1},
year = {2010}
}
@article{Chaves2005,
abstract = {Interactions between genes and gene products give rise to complex circuits that enable cells to process information and respond to external signals. Theoretical studies often describe these interactions using continuous, stochastic, or logical approaches. We propose a new modeling framework for gene regulatory networks, that combines the intuitive appeal of a qualitative description of gene states with a high flexibility in incorporating stochasticity in the duration of cellular processes. We apply our methods to the regulatory network of the segment polarity genes, thus gaining novel insights into the development of gene expression patterns. For example, we show that very short synthesis and decay times can perturb the wild-type pattern. On the other hand, separation of time-scales between pre- and post-translational processes and a minimal prepattern ensure convergence to the wild-type expression pattern regardless of fluctuations. {\textcopyright} 2005 Elsevier Ltd. All rights reserved.},
archivePrefix = {arXiv},
arxivId = {q-bio/0501037},
author = {Chaves, Madalena and Albert, R{\'{e}}ka and Sontag, Eduardo D.},
doi = {10.1016/j.jtbi.2005.01.023},
eprint = {0501037},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Chaves, Albert, Sontag - 2005 - Robustness and fragility of Boolean models for genetic regulatory networks.pdf:pdf},
isbn = {0022-5193 (Print)$\backslash$n0022-5193 (Linking)},
issn = {00225193},
journal = {Journal of Theoretical Biology},
keywords = {Boolean models,Gene regulatory networks,Segment polarity genes},
number = {3},
pages = {431--449},
pmid = {15882705},
primaryClass = {q-bio},
title = {{Robustness and fragility of Boolean models for genetic regulatory networks}},
volume = {235},
year = {2005}
}
@article{Damm2001,
abstract = {Telomerase, the ribonucleoprotein enzyme maintaining the telomeres of eukaryotic chromosomes, is active in most human cancers and in germline cells but, with few exceptions, not in normal human somatic tissues. Telomere maintenance is essential to the replicative potential of malignant cells and the inhibition of telomerase can lead to telomere shortening and cessation of unrestrained proliferation. We describe novel chemical compounds which selectively inhibit telomerase in vitro and in vivo. Treatment of cancer cells with these inhibitors leads to progressive telomere shortening, with no acute cytotoxicity, but a proliferation arrest after a characteristic lag period with hallmarks of senescence, including morphological, mitotic and chromosomal aberrations and altered patterns of gene expression. Telomerase inhibition and telomere shortening also result in a marked reduction of the tumorigenic potential of drug-treated tumour cells in a mouse xenograft model. This model was also used to demonstrate in vivo efficacy with no adverse side effects and uncomplicated oral administration of the inhibitor. These findings indicate that potent and selective, non-nucleosidic telomerase inhibitors can be designed as novel cancer treatment modalities.},
author = {Damm, Klaus and Hemmann, Ulrike and Garin-Chesa, Pilar and Hauel, Norbert and Kauffmann, Iris and Priepke, Henning and Niestroj, Claudia and Daiber, Christine and Enenkel, Barbara and Guilliard, Bernd and Lauritsch, Ines and M??ller, Elfriede and Pascolo, Emanuelle and Sauter, Gabriele and Pantic, Milena and Martens, Uwe M. and Wenz, Christian and Lingner, Joachim and Kraut, Norbert and Rettig, Wolfgang J. and Schnapp, Andreas},
doi = {10.1093/emboj/20.24.6958},
isbn = {0261-4189 (Print)$\backslash$r0261-4189 (Linking)},
issn = {02614189},
journal = {EMBO Journal},
keywords = {Cancer,Inhibitor,Microarray,Senescence,Telomerase},
number = {24},
pages = {6958--6968},
pmid = {11742973},
title = {{A highly selective telomerase inhibitor limiting human cancer cell proliferation}},
volume = {20},
year = {2001}
}
@article{Brosh2013,
abstract = {Helicases have major roles in genome maintenance by unwinding structured nucleic acids. Their prominence is marked by various cancers and genetic disorders that are linked to helicase defects. Although considerable effort has been made to understand the functions of DNA helicases that are important for genomic stability and cellular homeostasis, the complexity of the DNA damage response leaves us with unanswered questions regarding how helicase-dependent DNA repair pathways are regulated and coordinated with cell cycle checkpoints. Further studies may open the door to targeting helicases in order to improve cancer treatments based on DNA-damaging chemotherapy or radiation.},
archivePrefix = {arXiv},
arxivId = {15334406},
author = {Brosh, Robert M.},
doi = {10.1038/nrc3560},
eprint = {15334406},
isbn = {1474-175X},
issn = {1474-175X},
journal = {Nature Reviews Cancer},
number = {8},
pages = {542--558},
pmid = {23842644},
title = {{DNA helicases involved in DNA repair and their roles in cancer}},
url = {http://www.nature.com/doifinder/10.1038/nrc3560},
volume = {13},
year = {2013}
}
@article{Montagner2005,
abstract = {SHP2 was recently found to down-regulate PI3K activation by dephosphorylating Gab1 but the mechanisms explaining the positive role of the Gab1/SHP2 pathway in EGF-induced Ras activation remain ill defined. Substrate trapping experiments now suggest that SHP2 dephosphorylates other Gab1 phosphotyrosines located within a central region displaying four YXXP motifs. Because these sites are potential docking motifs for Ras-GAP, we tested whether SHP2 dephosphorylates them to facilitate Ras activation. We observed that a Gab1 construct preventing SHP2 recruitment promoted membrane relocation of RasGAP. Moreover, a RasGAP-inactive mutant restored the activation of Ras in cells transfected with SHP2-inactivating Gab1 mutant or in SHP2-deficient fibroblasts, supporting the hypothesis that RasGAP is a downstream target of SHP2. To determine whether Gab1 is a RasGAP-binding partner, a Gab1 mutant deleted of four YXXP motifs was produced. The deletion suppressed RasGAP redistribution and restored the defective Ras activation caused by SHP2-inactivating mutations. Moreover, Gab1 was found to interact with RasGAP SH2 domains, only under conditions where SHP2 is not activated. To identify Ras-GAP-binding sites, Tyr to Phe mutants of Gab1 YXXP motifs were produced. Gab1 constructs mutated on Tyr(317) were severely affected in RasGAP binding and were the most active in compensating for Ras-defective activation and blocking RasGAP redistribution induced by SHP2 inactivation. We have thus localized on Gab1 a Ras-negative regulatory tyrosine phosphorylation site involved in RasGAP binding and showed that an important SHP2 function is to down-regulate its phosphorylation to disengage RasGAP and sustain Ras activation.},
author = {Montagner, Alexandra and Yart, Armelle and Dance, Marie and Perret, Bertrand and Salles, Jean Pierre and Raynal, Patrick},
doi = {10.1074/jbc.M410012200},
isbn = {0021-9258 (Print)$\backslash$r0021-9258 (Linking)},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {15574420},
title = {{A novel role for Gab1 and SHP2 in epidermal growth factor-induced Ras activation}},
year = {2005}
}
@article{Song2016,
abstract = {Zinc-finger nuclease, transcription activator-like effector nuclease and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9) are becoming major tools for genome editing. Importantly, knock-in in several non-rodent species has been finally achieved thanks to these customizable nucleases; yet the rates remain to be further improved. We hypothesize that inhibiting non-homologous end joining (NHEJ) or enhancing homology-directed repair (HDR) will improve the nuclease-mediated knock-in efficiency. Here we show that the in vitro application of an HDR enhancer, RS-1, increases the knock-in efficiency by two- to five-fold at different loci, whereas NHEJ inhibitor SCR7 has minimal effects. We then apply RS-1 for animal production and have achieved multifold improvement on the knock-in rates as well. Our work presents tools to nuclease-mediated knock-in animal production, and sheds light on improving gene-targeting efficiencies on pluripotent stem cells.},
author = {Song, Jun and Yang, Dongshan and Xu, Jie and Zhu, Tianqing and Chen, Y. Eugene and Zhang, Jifeng},
doi = {10.1038/ncomms10548},
issn = {2041-1723},
journal = {Nature Communications},
pages = {10548},
pmid = {26817820},
title = {{RS-1 enhances CRISPR/Cas9- and TALEN-mediated knock-in efficiency}},
url = {http://www.nature.com/doifinder/10.1038/ncomms10548},
volume = {7},
year = {2016}
}
@article{Gunawardana2009,
abstract = {Nudix enzymes are a superfamily with a conserved common reaction mechanism that provides the capacity for the hydrolysis of a broad spectrum of metabolites. We used hidden Markov models based on Nudix sequences from the PFAM and PROSITE databases to identify Nudix hydrolases encoded by the Arabidopsis genome. 25 Nudix hydrolases were identified and classified into 11 individual families by pairwise sequence alignments. Intron phases were strikingly conserved in each family. Phylogenetic analysis showed that all multimember families formed monophyletic clusters. Conserved familial sequence motifs were identified with the MEME motif analysis algorithm. One motif (motif 4) was found in three diverse families. All proteins containing motif 4 demonstrated a degree of preference for substrates containing an ADP moiety. We conclude that HMM model-based genome scanning and MEME motif analysis, respectively, can significantly improve the identification and assignment of function of new members of this mechanistically-diverse protein superfamily.},
author = {Gunawardana, D. and Likic, V. A. and Gayler, K. R.},
doi = {10.1155/2009/820381},
isbn = {15316912},
issn = {15316912},
journal = {Comparative and Functional Genomics},
pmid = {19590748},
title = {{A comprehensive bioinformatics analysis of the nudix superfamily in Arabidopsis thaliana}},
volume = {2009},
year = {2009}
}
@techreport{Godfrey-Smith,
abstract = {Pacific Conservation Biology 19 (2013): 4-9. In thinking about the nature of the mind and its evolutionary history, cephalopods-especially octopuses, cuttlefish, and squid-have a special importance. These animals are an independent experiment in the evolution of large and complex nervous systems-in the biological machinery of the mind. They evolved this machinery on a historical lineage distant from our own. Where their minds differ from ours, they show us another way of being a sentient organism. Where we are similar, this is due to the convergence of distinct evolutionary paths. I introduced the topic just now as 'the mind.' This is a contentious term to use. What is it to have a mind? One option is that we are looking for something close to what humans have-something like reflective and conscious thought. This sets a high bar for having a mind. Another possible view is that whenever organisms adapt to their circumstances in real time by adjusting their behavior, taking in information and acting in response to it, there is some degree of mentality or intelligence there. To say this sets a low bar. It is best not to set bars in either place. Roughly speaking, we are dealing with a matter of degree, though 'degree' is not quite the right term either. The evolution of a mind is the acquisition of a tool-kit for the control of behavior. The tool-kit includes some kind of perception, though different animals have very different ways of taking in information from the world. It includes some form of memory and learning, means by which past experiences can be brought to bear on the present. In some cases it includes problem-solving and planning. Some tool-kits are more elaborate and expensive than others, but they can be sophisticated in different ways, with different tools present and more investment in one technology than another. One animal might have better ways of tracking the environment through its senses, while another may have simpler senses but more sophisticated learning. Different tool kits go with different ways of making a living. The ordinary term 'mind' is},
author = {Godfrey-Smith, Peter},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Godfrey-Smith - Unknown - Cephalopods and the Evolution of the Mind.pdf:pdf},
title = {{Cephalopods and the Evolution of the Mind}}
}
@article{Reo2002,
abstract = {Similar to genomics and proteomics which yield vast amounts of data about the expression of genes and proteins, metabolomics refers to the whole metabolic profile of the cell. The focus of this report concerns the use of nuclear magnetic resonance (NMR) spectroscopy for metabolic analyses and, in particular, its use in toxicology for examining the metabolic profile of biofluids. Examples from the literature will demonstrate how 1H NMR and pattern recognition methods are used to obtain the urinary metabolic profile, and how this profile is affected by exposure to various toxicants. These particular studies which focus on the metabolic profiles of biofluids, specifically urine, are referred to as metabonomics. NMR-based metabonomics provides a means to categorize organ-specific toxicity, monitor the onset and progression of toxicological effects, and identify biomarkers of toxicity. A future challenge, however, is to describe the cellular metabolome for purposes of understanding cellular functions (i.e., metabolomics). Thus the capabilities and advantages of multinuclear NMR to provide metabolic information in cells and tissues will also be discussed. Such information is essential if metabolomics is to provide a complementary dataset which together with genomics and proteomics can be used to construct computer network models to describe cellular functions.},
author = {Reo, Nicholas V.},
doi = {10.1081/DCT-120014789},
isbn = {0148-0545 (Print)$\backslash$r0148-0545 (Linking)},
issn = {0148-0545},
journal = {Drug and Chemical Toxicology},
number = {4},
pages = {375--382},
pmid = {12378948},
title = {{NMR-BASED METABOLOMICS}},
url = {http://www.tandfonline.com/doi/full/10.1081/DCT-120014789},
volume = {25},
year = {2002}
}
@article{Hopfensitz2013,
abstract = {Boolean networks are a popular class of models for the description of gene-regulatory networks. They model genes as simple binary variables, being either expressed or not expressed. Simulations of Boolean networks can give insights into the dynamics of cellular systems. In particular, stable states and cycles in the networks are thought to correspond to phenotypes. This paper presents approaches to identify attractors in synchronous, asynchronous and probabilistic Boolean networks and gives examples of their usage in the BoolNet R package.},
author = {Hopfensitz, Martin and M{\"{u}}ssel, Christoph and Maucher, Markus and Kestler, Hans A.},
doi = {10.1007/s00180-012-0324-2},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Hopfensitz et al. - 2013 - Attractors in Boolean networks A tutorial.pdf:pdf},
isbn = {0018001203},
issn = {09434062},
journal = {Computational Statistics},
keywords = {Attractors,Boolean networks,Systems biology},
title = {{Attractors in Boolean networks: A tutorial}},
year = {2013}
}
@article{Tong2001,
abstract = {In Saccharomyces cerevisiae, more than 80{\%} of the approximately 6200 predicted genes are nonessential, implying that the genome is buffered from the phenotypic consequences of genetic perturbation. To evaluate function, we developed a method for systematic construction of double mutants, termed synthetic genetic array (SGA) analysis, in which a query mutation is crossed to an array of approximately 4700 deletion mutants. Inviable double-mutant meiotic progeny identify functional relationships between genes. SGA analysis of genes with roles in cytoskeletal organization (BNI1, ARP2, ARC40, BIM1), DNA synthesis and repair (SGS1, RAD27), or uncharacterized functions (BBC1, NBP2) generated a network of 291 interactions among 204 genes. Systematic application of this approach should produce a global map of gene function.},
author = {Tong, A. H Y and Evangelista, M. and Parsons, A. B. and Xu, H. and Bader, G. D. and Pag{\'{e}}, N. and Robinson, M. and Raghibizadeh, S. and Hogue, C. W V and Bussey, H. and Andrews, B. and Tyers, M. and Boone, C.},
doi = {10.1126/science.1065810},
isbn = {0036-8075 (Print){\$}\backslash{\$}r0036-8075 (Linking)},
issn = {00368075},
journal = {Science},
number = {5550},
pages = {2364--2368},
pmid = {11743205},
title = {{Systematic genetic analysis with ordered arrays of yeast deletion mutants}},
volume = {294},
year = {2001}
}
@article{Prigent2011,
abstract = {The Rab GTPase-activating proteins (GAP) Gyp5p and Gyl1p are involved in the control of polarized exocytosis at the small-bud stage in Saccharomyces cerevisiae. Both Gyp5p and Gyl1p interact with the N-Bin1/Amphiphysin/Rvs167 (BAR) domain protein Rvs167p, but the biological function of this interaction is unclear. We show here that Gyp5p and Gyl1p recruit Rvs167p to the small-bud tip, where it plays a role in polarized exocytosis. In gyp5$\Delta$gyl1$\Delta$ cells, Rvs167p is not correctly localized to the small-bud tip. Both P473L mutation in the SH3 domain of Rvs167p and deletion of the proline-rich regions of Gyp5p and Gyl1p disrupt the interaction of Rvs167p with Gyp5p and Gyl1p and impair the localization of Rvs167p to the tips of small buds. We provide evidence for the accumulation of secretory vesicles in small buds of rvs167$\Delta$ cells and for defective Bgl2p secretion in rvs167$\Delta$ cultures enriched in small-budded cells at 13°C, implicating Rvs167p in polarized exocytosis. Moreover, both the accumulation of secretory vesicles in Rvs167p P473L cells cultured at 13°C and secretion defects in cells producing Gyp5p and Gyl1p without proline-rich regions strongly suggest that the function of Rvs167p in exocytosis depends on its ability to interact with Gyp5p and Gyl1p.},
author = {Prigent, Magali and Boy-Marcotte, Emmanuelle and Chesneau, Laurent and Gibson, Kimberley and Dupr{\'{e}}-Crochet, Sophie and Tisserand, H{\'{e}}l{\`{e}}ne and Verbavatz, Jean Marc and Cuif, Marie H{\'{e}}l{\`{e}}ne},
doi = {10.1111/j.1600-0854.2011.01218.x},
issn = {13989219},
journal = {Traffic},
keywords = {Gyl1p,Gyp5p,N-BAR domain,Polarized exocytosis,RabGAP,Rvs167p},
number = {8},
pages = {1084--1097},
pmid = {21554509},
title = {{The RabGAP proteins Gyp5p and Gyl1p recruit the BAR domain protein Rvs167p for polarized exocytosis}},
volume = {12},
year = {2011}
}
@article{Saez-Rodriguez2008,
abstract = {MOTIVATION Linking experimental data to mathematical models in biology is impeded by the lack of suitable software to manage and transform data. Model calibration would be facilitated and models would increase in value were it possible to preserve links to training data along with a record of all normalization, scaling, and fusion routines used to assemble the training data from primary results. RESULTS We describe the implementation of DataRail, an open source MATLAB-based toolbox that stores experimental data in flexible multi-dimensional arrays, transforms arrays so as to maximize information content, and then constructs models using internal or external tools. Data integrity is maintained via a containment hierarchy for arrays, imposition of a metadata standard based on a newly proposed MIDAS format, assignment of semantically typed universal identifiers, and implementation of a procedure for storing the history of all transformations with the array. We illustrate the utility of DataRail by processing a newly collected set of approximately 22 000 measurements of protein activities obtained from cytokine-stimulated primary and transformed human liver cells. AVAILABILITY DataRail is distributed under the GNU General Public License and available at http://code.google.com/p/sbpipeline/},
author = {Saez-Rodriguez, Julio and Goldsipe, Arthur and Muhlich, Jeremy and Alexopoulos, Leonidas G. and Millard, Bjorn and Lauffenburger, Douglas A. and Sorger, Peter K.},
doi = {10.1093/bioinformatics/btn018},
isbn = {1460-2059 (Electronic)},
issn = {13674803},
journal = {Bioinformatics},
pmid = {18218655},
title = {{Flexible informatics for linking experimental data to mathematical models via DataRail}},
year = {2008}
}
@article{Axelsson2011,
abstract = {1. Recent research has addressed howtransgenic residues fromarable cropsmay influence adjacent waterways, aquatic consumers and important ecosystem processes such as litter breakdown rates. With future applications of transgenic plants in forestry, such concerns may apply to forest stream ecosystems. Before any large-scale release of geneticallymodified (GM)trees, it is therefore impera- tive to evaluate the effects of geneticmodifications in trees on such ecosystems. 2. Weconducted decomposition experiments under natural streamconditions using leaf litter from greenhouse grownGMtrees (Populus tremula {\textperiodcentered} Populus tremuloides)thatexpress Bacillus thuringi- ensis (Bt) toxins (cry3Aa; targeting coleopteran leaf-feeding beetles) to examine the hypothesis that GMtreeswould affect litter decomposition rates and⁄or the aquatic arthropod community that col- onizes and feeds on leaf litter in streams. 3. We show that two independent transformations of isogenic Populus trees to express Bt toxins caused similar changes to the composition of aquatic insects colonizing the leaf litter, ultimately manifested in a 25{\%}and 33{\%}increases in average insect abundance. 4. Measurements of 24 phenolic compounds aswell as nitrogen (N) and carbon (C) in the litter did not significantly differ among modified and wild-type trees and were thus not sufficient to explain these differences in the insect assemblage. 5. Decomposition rates were comparable among litter treatments suggesting that the normal suite of leaf traits influencing decomposition was similar among litter treatments and that the shredding functions of the communityweremaintained despite the changes in insect community composition. 6. Synthesis and applications. We report that leaf litter fromGMtrees affected the composition of aquatic insect communities that colonized litter under natural stream conditions. This suggests that forest management using GM trees may affect adjacent waterways in unanticipated ways, which should be considered in future commercial applications ofGMtrees. We also argue that studies at different scales (e.g. species, communities and ecosystems) will be needed for a full understanding of the environmental effects of Bt plants.},
author = {Axelsson, E. Petter and Hj{\"{a}}lt{\'{e}}n, Joakim and Leroy, Carri J. and Whitham, Thomas G. and Julkunen-Tiitto, Riitta and Wennstr{\"{o}}m, Anders},
doi = {10.1111/j.1365-2664.2011.02046.x},
isbn = {0021-8901},
issn = {00218901},
journal = {Journal of Applied Ecology},
keywords = {Aquatic macroinvertebrates,Bacillus thuringiensis,Genetic modification,Leaf litter decomposition,Nontarget effects,Phytochemistry,Populus hybrids},
number = {6},
pages = {1472--1479},
title = {{Leaf litter from insect-resistant transgenic trees causes changes in aquatic insect community composition}},
volume = {48},
year = {2011}
}
@article{Watts1998,
abstract = {Networks of coupled dynamical systems have been used to model biological oscillators(1-4), Josephson junction arrays(5,6), excitable media(7), neural networks(8-10), spatial games(11), genetic control networks(12) and many other self-organizing systems. Ordinarily, the connection topology is assumed to be either completely regular or completely random. But many biological, technological and social networks lie somewhere between these two extremes. Here we explore simple models of networks that can be tuned through this middle ground: regular networks 'rewired' to introduce increasing amounts of disorder. We find that these systems can be highly clustered, like regular lattices, yet have small characteristic path lengths, like random graphs. We call them 'small-world' networks, by analogy with the small-world phenomenon(13,14) (popularly known as six degrees of separation(15)). The neural network of the worm Caenorhabditis elegans, the power grid of the western United States, and the collaboration graph of film actors are shown to be small-world networks. Models of dynamical systems with small-world coupling display enhanced signal-propagation speed, computational power, and synchronizability. In particular, infectious diseases spread more easily in small-world networks than in regular lattices.},
archivePrefix = {arXiv},
arxivId = {0803.0939v1},
author = {Watts, D J and Strogatz, S H},
doi = {Doi 10.1038/30918},
eprint = {0803.0939v1},
isbn = {0028-0836},
issn = {0028-0836},
journal = {Nature},
keywords = {chaos,disease,pulse-coupled oscillators,spread,synchronization},
pmid = {9623998},
title = {{Collective dynamics of'small-world' networks}},
year = {1998}
}
@article{Ryan2014,
abstract = {The directed evolution of biomolecules to improve or change their activity is central to many engineering and synthetic biology efforts. However, selecting improved variants from gene libraries in living cells requires plasmid expression systems that suffer from variable copy number effects, or the use of complex marker-dependent chromosomal integration strategies. We developed quantitative gene assembly and DNA library insertion into the Saccharomyces cerevisiae genome by optimizing an efficient single-step and marker-free genome editing system using CRISPR-Cas9. With this Multiplex CRISPR (CRISPRm) system, we selected an improved cellobiose utilization pathway in diploid yeast in a single round of mutagenesis and selection, which increased cellobiose fermentation rates by over ten-fold. Mutations recovered in the best cellodextrin transporters reveal synergy between substrate binding and transporter dynamics, and demonstrate the power of CRISPRm to accelerate selection experiments and discoveries of the molecular determinants that enhance biomolecule function.},
author = {Ryan, Owen W. and Skerker, Jeffrey M. and Maurer, Matthew J. and Li, Xin and Tsai, Jordan C. and Poddar, Snigdha and Lee, Michael E. and DeLoache, Will and Dueber, John E. and Arkin, Adam P. and Cate, Jamie H D},
doi = {10.7554/eLife.03703},
isbn = {10.1101/007310},
issn = {2050084X},
journal = {eLife},
number = {August2014},
pages = {1--15},
pmid = {25139909},
title = {{Selection of chromosomal DNA libraries using a multiplex CRISPR system}},
volume = {3},
year = {2014}
}
@article{Wang1998,
abstract = {Interleukin 3-dependent murine 32D cells do not detectably express members of the ErbB receptor family and do not proliferate in response to known ligands for these receptors. 32D transfectants were generated expressing human ErbB4 alone (32D.E4) or with ErbB2 (32D.E2/E4). Epidermal growth factor (EGF), neuregulin 1-beta (NRG1-beta), betacellulin (BTC), transforming growth factor-alpha (TGF-alpha), heparin binding-EGF (HB-EGF), and amphiregulin were analyzed for their ability to mediate mitogenesis in these transfectants. 32D.E4 responded mitogenically to NRG1-beta and BTC. Surprisingly, EGF also induced significant DNA synthesis and TGF-alpha was negligibly mitogenic on 32D.E4 cells, whereas HB-EGF and amphiregulin were inactive. Although coexpression of ErbB2 with ErbB4 in 32D.E2/E4 cells did not significantly alter DNA synthesis in response to NRG1-beta or BTC, it greatly enhanced mitogenesis elicited by EGF and TGF-alpha and unmasked the ability of HB-EGF to induce proliferation. EGF-related ligands that exhibited potent mitogenic activity on 32D.E2/E4 cells at low concentrations induced adherence, morphological alterations, and up-regulation of the Mac-1 integrin and FcgammaRII/III at higher concentrations. While 125I-EGF could be specifically crosslinked to both 32D.E4 and 32D.E2/E4 cells, its crosslinking capacity was greatly enhanced in the cotransfected cells. The ability of the various ligands to mediate proliferation and/or adhesion in the two transfectants correlated with their capacity to induce substrate tyrosine phosphorylation and to initiate and sustain activation of mitogen-activated protein kinase. We conclude that the ability of ErbB4 to mediate signal transduction through EGF-like ligands is broader than previously assumed and can be profoundly altered by the concomitant expression of ErbB2.},
author = {Wang, L.-M. and Kuo, A. and Alimandi, M. and Veri, M. C. and Lee, C.-C. and Kapoor, V. and Ellmore, N. and Chen, X.-H. and Pierce, J. H.},
doi = {10.1073/pnas.95.12.6809},
isbn = {0027-8424 (Print)$\backslash$r0027-8424 (Linking)},
issn = {0027-8424},
journal = {Proceedings of the National Academy of Sciences},
pmid = {9618494},
title = {{ErbB2 expression increases the spectrum and potency of ligand-mediated signal transduction through ErbB4}},
year = {1998}
}
@article{Michaels1992,
abstract = {Active oxygen species can damage DNA and may play a role in aging and carcinogenesis. We have tested MutY glycosylase for activity on undamaged mispairs as well as mispairs formed with the oxidatively damaged substrates, 8-oxo-7,8-dihydrodeoxyguanine (GO) or 8-oxo-7,8-dihydrodeoxyadenine (AO). MutY acts as a glycosylase on four of the heteroduplexes tested, A/G, A/GO, A/C, and A/AO, removing the undamaged adenine from each substrate. Genetic data suggest that the primary substrate for MutY glycosylase in vivo is the A/GO mispair. We present biochemical evidence demonstrating that MutY glycosylase is an important part of a repair system that includes the MutM and MutT proteins. The GO repair system is dedicated to the repair of the oxidatively damaged guanine and the mutations it can induce.},
author = {Michaels, M L and Tchou, J and Grollman, a P and Miller, J H},
doi = {10.1021/bi00160a004},
isbn = {0006-2960 (Print)$\backslash$r0006-2960 (Linking)},
issn = {0006-2960},
journal = {Biochemistry},
number = {45},
pages = {10964--10968},
pmid = {1445834},
title = {{A repair system for 8-oxo-7,8-dihydrodeoxyguanine.}},
volume = {31},
year = {1992}
}
@article{Calzone2008,
abstract = {We present, here, a detailed and curated map of molecular interactions taking place in the regulation of the cell cycle by the retinoblastoma protein (RB/RB1). Deregulations and/or mutations in this pathway are observed in most human cancers. The map was created using Systems Biology Graphical Notation language with the help of CellDesigner 3.5 software and converted into BioPAX 2.0 pathway description format. In the current state the map contains 78 proteins, 176 genes, 99 protein complexes, 208 distinct chemical species and 165 chemical reactions. Overall, the map recapitulates biological facts from approximately 350 publications annotated in the diagram. The network contains more details about RB/E2F interaction network than existing large-scale pathway databases. Structural analysis of the interaction network revealed a modular organization of the network, which was used to elaborate a more summarized, higher-level representation of RB/E2F network. The simplification of complex networks opens the road for creating realistic computational models of this regulatory pathway.},
author = {Calzone, Laurence and Gelay, Am{\'{e}}lie and Zinovyev, Andrei and Radvanyi, Fran{\c{c}}ois and Barillot, Emmanuel},
doi = {10.1038/msb.2008.7},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Calzone et al. - 2008 - A comprehensive modular map of molecular interactions in RBE2F pathway.pdf:pdf},
isbn = {1744-4292},
issn = {1744-4292},
journal = {Molecular Systems Biology},
pmid = {18319725},
title = {{A comprehensive modular map of molecular interactions in RB/E2F pathway}},
year = {2008}
}
@article{Chu2015,
abstract = {The insertion of precise genetic modifications by genome editing tools such as CRISPR-Cas9 is limited by the relatively low efficiency of homology-directed repair (HDR) compared with the higher efficiency of the nonhomologous end-joining (NHEJ) pathway. To enhance HDR, enabling the insertion of precise genetic modifications, we suppressed the NHEJ key molecules KU70, KU80 or DNA ligase IV by gene silencing, the ligase IV inhibitor SCR7 or the coexpression of adenovirus 4 E1B55K and E4orf6 proteins in a 'traffic light' and other reporter systems. Suppression of KU70 and DNA ligase IV promotes the efficiency of HDR 4-5-fold. When co-expressed with the Cas9 system, E1B55K and E4orf6 improved the efficiency of HDR up to eightfold and essentially abolished NHEJ activity in both human and mouse cell lines. Our findings provide useful tools to improve the frequency of precise gene modifications in mammalian cells.},
author = {Chu, Van Trung and Weber, Timm and Wefers, Benedikt and Wurst, Wolfgang and Sander, Sandrine and Rajewsky, Klaus and K{\"{u}}hn, Ralf},
doi = {10.1038/nbt.3198},
isbn = {1546-1696 (Electronic)$\backslash$r1087-0156 (Linking)},
issn = {1087-0156},
journal = {Nature Biotechnology},
number = {5},
pages = {543--548},
pmid = {25803306},
title = {{Increasing the efficiency of homology-directed repair for CRISPR-Cas9-induced precise gene editing in mammalian cells}},
url = {http://www.nature.com/doifinder/10.1038/nbt.3198},
volume = {33},
year = {2015}
}
@misc{Weng1999,
abstract = {Biological signaling pathways interact with one another to form complex networks. Complexity arises from the large number of components, many with isoforms that have partially overlapping functions; from the connections among components; and from the spatial relationship between components. The origins of the complex behavior of signaling networks and analytical approaches to deal with the emergent complexity are discussed here.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Weng, Gezhi and Bhalla, Upinder S. and Iyengar, Ravi},
booktitle = {Science},
doi = {10.1126/science.284.5411.92},
eprint = {NIHMS150003},
isbn = {1191001202},
issn = {00368075},
pmid = {10102825},
title = {{Complexity in biological signaling systems}},
year = {1999}
}
@article{Overall2012,
abstract = {BACKGROUND: Adult hippocampal neurogenesis is not a single phenotype, but consists of a number of sub-processes, each of which is under complex genetic control. Interpretation of gene expression studies using existing resources often does not lead to results that address the interrelatedness of these processes. Formal structure, such as provided by ontologies, is essential in any field for comprehensive interpretation of existing knowledge but, until now, such a structure has been lacking for adult neurogenesis.$\backslash$n$\backslash$nMETHODOLOGY/PRINCIPAL FINDINGS: We have created a resource with three components 1. A structured ontology describing the key stages in the development of adult hippocampal neural stem cells into functional granule cell neurons. 2. A comprehensive survey of the literature to annotate the results of all published reports on gene function in adult hippocampal neurogenesis (257 manuscripts covering 228 genes) to the appropriate terms in our ontology. 3. An easy-to-use searchable interface to the resulting database made freely available online. The manuscript presents an overview of the database highlighting global trends such as the current bias towards research on early proliferative stages, and an example gene set enrichment analysis. A limitation of the resource is the current scope of the literature which, however, is growing by around 100 publications per year. With the ontology and database in place, new findings can be rapidly annotated and regular updates of the database will be made publicly available.$\backslash$n$\backslash$nCONCLUSIONS/SIGNIFICANCE: The resource we present allows relevant interpretation of gene expression screens in terms of defined stages of postnatal neuronal development. Annotation of genes by hand from the adult neurogenesis literature ensures the data are directly applicable to the system under study. We believe this approach could also serve as an example to other fields in a 'bottom-up' community effort complementing the already successful 'top-down' approach of the Gene Ontology.},
author = {Overall, Rupert W. and Paszkowski-Rogacz, Maciej and Kempermann, Gerd},
doi = {10.1371/journal.pone.0048527},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Overall, Paszkowski-Rogacz, Kempermann - 2012 - The Mammalian Adult Neurogenesis Gene Ontology (MANGO) Provides a Structural Framework f.pdf:pdf},
isbn = {1932-6203 (Electronic)$\backslash$r1932-6203 (Linking)},
issn = {19326203},
journal = {PLoS ONE},
number = {11},
pmid = {23139788},
title = {{The Mammalian Adult Neurogenesis Gene Ontology (MANGO) Provides a Structural Framework for Published Information on Genes Regulating Adult Hippocampal Neurogenesis}},
volume = {7},
year = {2012}
}
@article{Cross1995,
abstract = {Glycogen synthase kinase-3 (GSK3) is implicated in the regulation of several physiological processes, including the control of glycogen and protein synthesis by insulin, modulation of the transcription factors AP-1 and CREB, the specification of cell fate in Drosophila and dorsoventral patterning in Xenopus embryos. GSK3 is inhibited by serine phosphorylation in response to insulin or growth factors and in vitro by either MAP kinase-activated protein (MAPKAP) kinase-1 (also known as p90rsk) or p70 ribosomal S6 kinase (p70S6k). Here we show, however, that agents which prevent the activation of both MAPKAP kinase-1 and p70S6k by insulin in vivo do not block the phosphorylation and inhibition of GSK3. Another insulin-stimulated protein kinase inactivates GSK3 under these conditions, and we demonstrate that it is the product of the proto-oncogene protein kinase B (PKB, also known as Akt/RAC). Like the inhibition of GSK3 (refs 10, 14), the activation of PKB is prevented by inhibitors of phosphatidylinositol (PI) 3-kinase.},
author = {Cross, Darren A.E. and Alessi, Dario R. and Cohen, Philip and Andjelkovich, Mirjana and Hemmings, Brian A.},
doi = {10.1038/378785a0},
isbn = {0028-0836 (Print)$\backslash$r0028-0836 (Linking)},
issn = {00280836},
journal = {Nature},
pmid = {8524413},
title = {{Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B}},
year = {1995}
}
@misc{Verma2005,
abstract = {Compounds that have unexpected biological activity and are unable to fit in a QSAR model are known as outliers. These are valuable in defining the limitations under which compounds act by a common molecular mechanism modeled by one or more descriptors, and also in defining the experimental limitations of the biological test data. Thus, the outliers should be submitted to particular attention to see if the reason for their peculiarity can be determined. Separating these outliers from the main data set and formulating another QSAR can resolve the problem. Our result shows that these outliers may be acting by a different mechanism or interacting with the receptor in different modes. ?? 2005 Elsevier Ltd. All rights reserved.},
author = {Verma, Rajeshwar P. and Hansch, Corwin},
booktitle = {Bioorganic and Medicinal Chemistry},
doi = {10.1016/j.bmc.2005.05.002},
isbn = {0968-0896},
issn = {09680896},
keywords = {Hydrophobicity,Molar refractivity,Molar volume,Outlier,Structure-activity relationships},
number = {15},
pages = {4597--4621},
pmid = {15951183},
title = {{An approach toward the problem of outliers in QSAR}},
volume = {13},
year = {2005}
}
@article{Prudent2005,
abstract = {Osmoregulation plays an important role in cellular responses to osmotic stress in plants and in yeast. Aquaporins contribute to osmotic adjustment by facilitating transport of water or solutes across membranes. The tonoplastic water channel BobTIP1;1 (original name BobTIP26-1) genes are upregulated during dessication stress in cauliflower meristematic tissue. To investigate the physiological importance of BobTIP1;1, we expressed it in a Saccharomyces cerevisiae osmosensitive mutant fps1$\Delta$. We showed that the defect in the yeast glycerol plasma membrane transporter is complemented by a plant cDNA encoding the aquaporin BobTIP1;1 which is localized in the vacuolar membrane of the complemented yeast cells. To our knowledge, this is the first example of a plant aquaporin for which localization in the vacuolar membrane of yeast cells is related to an osmoresistant phenotype under hypo-osmotic shock. {\textcopyright} 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.},
author = {Prudent, S{\'{e}}bastien and Marty, Francis and Charbonnier, Maryse},
doi = {10.1016/j.febslet.2005.05.076},
isbn = {0014-5793 (Print)$\backslash$r0014-5793 (Linking)},
issn = {00145793},
journal = {FEBS Letters},
keywords = {Aquaporin,Hypo-osmotic shock,Osmotic stress,Vacuolar membrane,$\gamma$-TIP},
number = {18},
pages = {3872--3880},
pmid = {16004998},
title = {{The yeast osmosensitive mutant fps1$\Delta$ transformed by the cauliflower BobTIP1;1 aquaporin withstand a hypo-osmotic shock}},
volume = {579},
year = {2005}
}
@misc{Dibble2015,
abstract = {The class I phosphoinositide 3-kinase (PI3K)-mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signaling network directs cellular metabolism and growth. Activation of mTORC1 [composed of mTOR, regulatory-associated protein of mTOR (Raptor), mammalian lethal with SEC13 protein 8. (mLST8), 40-kDa proline-rich Akt substrate (PRAS40), and DEP domain-containing mTOR-interacting protein (DEPTOR)] depends on the Ras-related GTPases (Rags) and Ras homolog enriched in brain (Rheb) GTPase and requires signals from amino acids, glucose, oxygen, energy (ATP), and growth factors (including cytokines and hormones such as insulin). Here we discuss the signal transduction mechanisms through which growth factor-responsive PI3K signaling activates mTORC1. We focus on how PI3K-dependent activation of Akt and spatial regulation of the tuberous sclerosis complex (TSC) complex (TSC complex) [composed of TSC1, TSC2, and Tre2-Bub2-Cdc16-1 domain family member 7 (TBC1D7)] switches on Rheb at the lysosome, where mTORC1 is activated. Integration of PI3K- and amino acid-dependent signals upstream of mTORC1 at the lysosome is detailed in a working model. A coherent understanding of the PI3K-mTORC1 network is imperative as its dysregulation has been implicated in diverse pathologies including cancer, diabetes, autism, and aging.},
archivePrefix = {arXiv},
arxivId = {15334406},
author = {Dibble, Christian C. and Cantley, Lewis C.},
booktitle = {Trends in Cell Biology},
doi = {10.1016/j.tcb.2015.06.002},
eprint = {15334406},
isbn = {1879-3088 (Electronic)$\backslash$r0962-8924 (Linking)},
issn = {18793088},
keywords = {Insulin,Lysosome,Rag,Raptor,Rheb,TSC2},
pmid = {26159692},
title = {{Regulation of mTORC1 by PI3K signaling}},
year = {2015}
}
@article{Terfve2012,
abstract = {BACKGROUND Cells process signals using complex and dynamic networks. Studying how this is performed in a context and cell type specific way is essential to understand signaling both in physiological and diseased situations. Context-specific medium/high throughput proteomic data measured upon perturbation is now relatively easy to obtain but formalisms that can take advantage of these features to build models of signaling are still comparatively scarce. RESULTS Here we present CellNOptR, an open-source R software package for building predictive logic models of signaling networks by training networks derived from prior knowledge to signaling (typically phosphoproteomic) data. CellNOptR features different logic formalisms, from Boolean models to differential equations, in a common framework. These different logic model representations accommodate state and time values with increasing levels of detail. We provide in addition an interface via Cytoscape (CytoCopteR) to facilitate use and integration with Cytoscape network-based capabilities. CONCLUSIONS Models generated with this pipeline have two key features. First, they are constrained by prior knowledge about the network but trained to data. They are therefore context and cell line specific, which results in enhanced predictive and mechanistic insights. Second, they can be built using different logic formalisms depending on the richness of the available data. Models built with CellNOptR are useful tools to understand how signals are processed by cells and how this is altered in disease. They can be used to predict the effect of perturbations (individual or in combinations), and potentially to engineer therapies that have differential effects/side effects depending on the cell type or context.},
author = {Terfve, Camille and Cokelaer, Thomas and Henriques, David and MacNamara, Aidan and Goncalves, Emanuel and Morris, Melody K. and van Iersel, Martijn and Lauffenburger, Douglas A. and Saez-Rodriguez, Julio},
doi = {10.1186/1752-0509-6-133},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Terfve et al. - 2012 - CellNOptR A flexible toolkit to train protein signaling networks to data using multiple logic formalisms.pdf:pdf},
isbn = {1752-0509},
issn = {17520509},
journal = {BMC Systems Biology},
keywords = {Logic modeling,Perturbation data,Phosphoproteomics,Signaling networks,Systems biology},
pmid = {23079107},
title = {{CellNOptR: A flexible toolkit to train protein signaling networks to data using multiple logic formalisms}},
volume = {6},
year = {2012}
}
@article{Stamford1984,
abstract = {High speed cyclic voltammetry was used in combination with pressure ejection of ascorbate oxidase for the determination of extracellular ascorbic acid within the brain of the anaesthetized rat. Large variations in absolute levels of ascorbate were found between animals although distribution patterns showed a good degree of reproducibility. Ascorbate levels in the white matter of the corpus callosum were found to be higher than in adjacent areas of grey matter (striatum and cortex).},
author = {Stamford, J a and Kruk, Z L and Millar, J},
doi = {0006-8993(84)90710-8 [pii]},
isbn = {0006-8993 (Print)$\backslash$r0006-8993 (Linking)},
issn = {0006-8993},
journal = {Brain research},
keywords = {Animals,Ascorbic Acid,Ascorbic Acid: analysis,Brain Chemistry,Cerebral Cortex,Cerebral Cortex: analysis,Corpus Callosum,Corpus Callosum: analysis,Corpus Striatum,Corpus Striatum: analysis,Electrochemistry,Electrochemistry: methods,Male,Rats,Rats, Inbred Strains},
number = {2},
pages = {289--95},
pmid = {6733451},
title = {{Regional differences in extracellular ascorbic acid levels in the rat brain determined by high speed cyclic voltammetry.}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/6733451},
volume = {299},
year = {1984}
}
@article{Ogawara2002,
abstract = {p53 plays a key role in DNA damage-induced apoptosis. Recent studies have reported that the phosphatidylinositol 3-OH-kinase-Akt pathway inhibits p53-mediated transcription and apoptosis, although the underlying mechanisms have yet to be determined. Mdm2, a ubiquitin ligase for p53, plays a central role in regulation of the stability of p53 and serves as a good substrate for Akt. In this study, we find that expression of Akt reduces the protein levels of p53, at least in part by enhancing the degradation of p53. Both Akt expression and serum treatment induced phosphorylation of Mdm2 at Ser186. Akt-mediated phosphorylation of Mdm2 at Ser186 had little effect on the subcellular localization of Mdm2. However, both Akt expression and serum treatment increased Mdm2 ubiquitination of p53. The serum-induced increase in p53 ubiquitination was blocked by LY294002, a phosphatidylinositol 3-OH-kinase inhibitor. Moreover, when Ser186 was replaced by Ala, Mdm2 became resistant to Akt enhancement of p53 ubiquitination and degradation. Collectively, these results suggest that Akt enhances the ubiquitination-promoting function of Mdm2 by phosphorylation of Ser186, which results in reduction of p53 protein. This study may shed light on the mechanisms by which Akt promotes survival, proliferation, and tumorigenesis.},
author = {Ogawara, Yoko and Kishishita, Shohei and Obata, Toshiyuki and Isazawa, Yuko and Suzuki, Toshiaki and Tanaka, Keiji and Masuyama, Norihisa and Gotoh, Yukiko},
doi = {10.1074/jbc.M109745200},
isbn = {2184321850},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {11923280},
title = {{Akt enhances Mdm2-mediated ubiquitination and degradation of p53}},
year = {2002}
}
@article{VanderGeer1995,
abstract = {Background: Signal transduction by growth factor receptor protein-tyrosine kinases is generally initiated by autophosphorylation on tyrosine residues following ligand binding. Phosphotyrosines within activated receptors form binding sites for the Src homology 2 (SH2) domains of cytoplasmic signalling proteins. One such protein, Shc, is tyrosine phosphorylated in response to a large number of growth factors and cytokines. Phosphorylation of Shc on tyrosine residue Y317 allows binding to the SH2 domain of Grb2, and hence stimulation of the Ras pathway. Shc is therefore implicated as an adaptor protein able to couple normal and oncogenic protein-tyrosine kinases to Ras activation. Shc itself contains an SH2 domain at its carboxyl terminus, but the function of the amino-terminal half of the protein is unknown. Results We have found that the Shc amino-terminal region binds to a number of tyrosine-phosphorylated proteins in v-src-transformed cells. This domain also bound directly to the activated epidermal growth factor (EGF) receptor. A phosphotyrosine (pY)-containing peptide modeled after the Shc-binding site in polyoma middle T antigen (LLSNPTpYSVMRSK) was able to compete efficiently with the activated EGF receptor for binding to the Shc amino terminus. This competition was dependent on phosphorylation of the tyrosine residue within the peptide, and was abrogated by deletion of the leucine residue at position -5. The Shc amino-terminal domain also bound to the autophosphorylated nerve growth factor receptor (Trk), but bound significantly less well to a mutant receptor in which tyrosine Y490 in the receptor's Shc-binding site had been substituted by phenylalanine. Conclusion These data implicate the amino-terminal region of Shc in binding to activated receptors and other tyrosine-phosphorylated proteins. Binding appears to be specific for phosphorylated tyrosine residues within the sequence NPXpY, which is conserved in many Shc-binding sites. The Shc amino-terminal region bears only very limited sequence identity to known SH2 domains, suggesting that it represents a new class of phosphotyrosine-binding modules. Consistent with this view, the amino-terminal Shc domain is highly conserved in a Drosophila Shc homologue. Binding of Shc to activated receptors through its amino terminus could leave the carboxy-terminal SH2 domain free for other interactions. In this way, Shc may function as an adaptor protein to bring two tyrosine-phosphorylated proteins together. {\textcopyright} 1995 Elsevier Science Ltd. All rights reserved.},
author = {van der Geer, Peter and Wiley, Sandra and {Ka-Man Lai}, Venus and Olivier, Jean Paul and Gish, Gerald D. and Stephens, Robert and Kaplan, David and Shoelson, Steven and Pawson, Tony},
doi = {10.1016/S0960-9822(95)00081-9},
isbn = {0960-9822 (Print)$\backslash$r0960-9822 (Linking)},
issn = {09609822},
journal = {Current Biology},
pmid = {7542991},
title = {{A conserved amino-terminal Shc domain binds to phosphotyrosine motifs in activated receptors and phosphopeptides}},
year = {1995}
}
@article{Chen2013,
abstract = {Next-generation-sequencing (NGS) has revolutionized the field of genome assembly because of its much higher data throughput and much lower cost compared with traditional Sanger sequencing. However, NGS poses new computational challenges to de novo genome assembly. Among the challenges, GC bias in NGS data is known to aggravate genome assembly. However, it is not clear to what extent GC bias affects genome assembly in general. In this work, we conduct a systematic analysis on the effects of GC bias on genome assembly. Our analyses reveal that GC bias only lowers assembly completeness when the degree of GC bias is above a threshold. At a strong GC bias, the assembly fragmentation due to GC bias can be explained by the low coverage of reads in the GC-poor or GC-rich regions of a genome. This effect is observed for all the assemblers under study. Increasing the total amount of NGS data thus rescues the assembly fragmentation because of GC bias. However, the amount of data needed for a full rescue depends on the distribution of GC contents. Both low and high coverage depths due to GC bias lower the accuracy of assembly. These pieces of information provide guidance toward a better de novo genome assembly in the presence of GC bias.},
author = {Chen, Yen Chun and Liu, Tsunglin and Yu, Chun Hui and Chiang, Tzen Yuh and Hwang, Chi Chuan},
doi = {10.1371/journal.pone.0062856},
isbn = {1932-6203},
issn = {19326203},
journal = {PLoS ONE},
number = {4},
pmid = {23638157},
title = {{Effects of GC Bias in Next-Generation-Sequencing Data on De Novo Genome Assembly}},
volume = {8},
year = {2013}
}
@misc{Albert2003,
abstract = {Expression of the Drosophila segment polarity genes is initiated by a pre-pattern of pair-rule gene products and maintained by a network of regulatory interactions throughout several stages of embryonic development. Analysis of a model of gene interactions based on differential equations showed that wild-type expression patterns of these genes can be obtained for a wide range of kinetic parameters, which suggests that the steady states are determined by the topology of the network and the type of regulatory interactions between components, not the detailed form of the rate laws. To investigate this, we propose and analyse a Boolean model of this network which is based on a binary ON/OFF representation of mRNA and protein levels, and in which the interactions are formulated as logical functions. In this model the spatial and temporal patterns of gene expression are determined by the topology of the network and whether components are present or absent, rather than the absolute levels of the mRNAs and proteins and the functional details of their interactions. The model is able to reproduce the wild-type gene expression patterns, as well as the ectopic expression patterns observed in overexpression experiments and various mutants. Furthermore, we compute explicitly all steady states of the network and identify the basin of attraction of each steady state. The model gives important insights into the functioning of the segment polarity gene network, such as the crucial role of the wingless and sloppy paired genes, and the network's ability to correct errors in the pre-pattern. {\textcopyright} 2003 Elsevier Science Ltd. All rights reserved.},
archivePrefix = {arXiv},
arxivId = {arXiv:q-bio/0311019v1},
author = {Albert, R{\'{e}}ka and Othmer, Hans G.},
booktitle = {Journal of Theoretical Biology},
doi = {10.1016/S0022-5193(03)00035-3},
eprint = {0311019v1},
isbn = {0022-5193 (Print)$\backslash$r0022-5193 (Linking)},
issn = {00225193},
keywords = {Boolean model,Drosophila segmentation,Gene regulatory network,Segment polarity genes},
pmid = {12782112},
primaryClass = {arXiv:q-bio},
title = {{The topology of the regulatory interactions predicts the expression pattern of the segment polarity genes in Drosophila melanogaster}},
year = {2003}
}
@article{Kuzmin2016,
abstract = {Genetic interaction studies have been used to characterize unknown genes, assign membership in pathway and complex, and build a comprehensive functional map of a eukaryotic cell. Synthetic genetic array (SGA) methodology automates yeast genetic analysis and enables systematic mapping of genetic interactions. In its simplest form, SGA consists of a series of replica pinning steps that enable construction of haploid double mutants through automated mating and meiotic recombination. Using this method, a strain carrying a query mutation, such as a deletion allele of a nonessential gene or a conditional temperature-sensitive allele of an essential gene, can be crossed to an input array of yeast mutants, such as the complete set of approximately 5000 viable deletion mutants. The resulting output array of double mutants can be scored for genetic interactions based on estimates of cellular fitness derived from colony-size measurements. The SGA score method can be used to analyze large-scale data sets, whereas small-scale data sets can be analyzed using SGAtools, a simple web-based interface that includes all the necessary analysis steps for quantifying genetic interactions.},
author = {Kuzmin, Elena and Costanzo, Michael and Andrews, Brenda and Boone, Charles},
doi = {10.1101/pdb.prot088807},
issn = {15596095},
journal = {Cold Spring Harbor Protocols},
number = {4},
pages = {359--372},
pmid = {27037072},
title = {{Synthetic genetic array analysis}},
volume = {2016},
year = {2016}
}
@book{Equation,
author = {Equation, Structural},
file = {:Users/ozlem/Desktop/SEM/PP{\_}SEM{\_}3e.pdf:pdf},
isbn = {9781606238776},
title = {{No Title}}
}
@misc{Moukharskaya2012,
abstract = {Topoisomerase 1 inhibitors cure human cancer xenografts in animal models, more so than most other chemotherapy agents. However, their activity in patients with cancer is modest. Ongoing research is studying the optimal analogues that could reproduce animal data in the cancer population. This article analyzes the clinical research with topoisomerase 1 inhibitors in ovarian cancer. ?? 2012 Elsevier Inc..},
author = {Moukharskaya, Julia and Verschraegen, Claire},
booktitle = {Hematology/Oncology Clinics of North America},
doi = {10.1016/j.hoc.2012.03.002},
issn = {08898588},
keywords = {Irinotecan,Ovarian cancer,Topoisomerase 1,Topotecan},
number = {3},
pages = {507--525},
pmid = {22520977},
title = {{Topoisomerase 1 Inhibitors and Cancer Therapy}},
volume = {26},
year = {2012}
}
@article{Abu-El-Haija2018,
abstract = {The mTOR kinase controls cell growth, proliferation, and survival through two distinct multiprotein complexes, mTORC1 and mTORC2. mTOR and mLST8 are in both complexes, while raptor and rictor are part of only mTORC1 and mTORC2, respectively. To investigate mTORC1 and mTORC2 function in vivo, we generated mice deficient for raptor, rictor, or mLST8. Like mice null for mTOR, those lacking raptor die early in development. However, mLST8 null embryos survive until e10.5 and resemble embryos missing rictor. mLST8 is necessary to maintain the rictor-mTOR, but not the raptor-mTOR, interaction, and both mLST8 and rictor are required for the hydrophobic motif phosphorylation of Akt/PKB and PKC$\alpha$, but not S6K1. Furthermore, insulin signaling to FOXO3, but not to TSC2 or GSK3$\beta$, requires mLST8 and rictor. Thus, mTORC1 function is essential in early development, mLST8 is required only for mTORC2 signaling, and mTORC2 is a necessary component of the Akt-FOXO and PKC$\alpha$ pathways. {\textcopyright} 2006 Elsevier Inc. All rights reserved.},
author = {Abu-El-Haija, Maisam and Uc, Aliye and Werlin, Steven L. and Freeman, Alvin Jay and Georgieva, Miglena and Jojki{\'{c}}-Pavkov, Danijela and Kalnins, Daina and Kochavi, Brigitte and Koot, Bart G.P. and {Van Biervliet}, Stephanie and Walkowiak, Jaroslaw and Wilschanski, Michael and Morinville, Veronique D.},
doi = {10.1016/j.devcel.2006.10.007},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/PIIS153458070600459X.pdf:pdf},
isbn = {1534-5807},
issn = {15345807},
journal = {Journal of Pediatric Gastroenterology and Nutrition},
number = {1},
pages = {131--143},
pmid = {17141160},
title = {{Nutritional Considerations in Pediatric Pancreatitis}},
url = {http://insights.ovid.com/crossref?an=00005176-201807000-00023},
volume = {67},
year = {2018}
}
@article{Vauramo2006,
abstract = {Although the area under cultivation of genetically modified plants (GMPs) has substantially increased during the last decade, the effects of transgenic organisms on ecosystem processes (such as litter decomposition and nutrient cycling) largely remain unknown. In this study, the decomposition of leaf litter from transgenic birch trees (Betula pendula) expressing sugar beet chitinase IV gene was studied in a field experiment. Eight chitinase transgenic lines and a non-transgenic control were included in the study. The decomposition of these litters was investigated by studying: (i) litter mass loss, (ii) fungal (litter ergosterol content) and total microbial biomass (SIR) and their activity (basal respiration), and (iii) the effects of transgenic litter on microbial-feeding soil fauna (number of nematodes and abundance of different functional groups). At the end of the study (8 and 11 months after establishment) mass loss of chitinase transgenic leaf litter did not differ from that of non-transgenic control trees. Similarly, no differences in either the fungal or total microbial biomass between the treatments were recorded. A single transgenic line showing high chitinase IV expression differed significantly from the controls in the mean number of nematodes. The nematode populations in this litter showed distinct temporal dynamics compared to the controls, thus indirectly indicating microbial differences in the litter. The results of this study indicate that conceivable changes, possibly derived from pleiotropic effects due to gene modification, in the litter quality due to gene transformation are either absent or too weak to affect the decomposability of the litter in the soil. {\textcopyright} 2005 Elsevier B.V. All rights reserved.},
author = {Vauramo, Saara and Pasonen, Hanna Leena and Pappinen, Ari and Set{\"{a}}l{\"{a}}, Heikki},
doi = {10.1016/j.apsoil.2005.07.007},
isbn = {0929-1393},
issn = {09291393},
journal = {Applied Soil Ecology},
keywords = {Betula pendula,Chitinase,Decomposition,Litter bag experiment,Nematodes,Transgenic tree},
number = {3},
pages = {338--349},
title = {{Decomposition of leaf litter from chitinase transgenic silver birch (Betula pendula) and effects on decomposer populations in a field trial}},
volume = {32},
year = {2006}
}
@article{Pantic2015,
abstract = {Several laboratories have recently published the findings indicating that nanomaterial-based biosensors could be very effective in detection of neurotransmitters in biological samples. Most of the research has been focused on monoamine neurotransmitters such as dopamine, serotonin and norepinephrine. These novel approaches have mostly been tested in in vitro conditions, however, there are indications that they might be also safely and effectively used in living organisms. In this concise review, we focus on the recent publications regarding the detection and measurement of monoamine neurotransmitters using nano-based sensors. We cover the research done during the past 5 years in the fileds nanotechnology and nanomedicine. Finally, we discuss potential future approaches and trends in these research areas, as well as issues and challenges that scientists are faced with, when performing experimental or clinical work with nanomaterials.},
author = {Pantic, Igor and Paunovic, Jovana and Dimitrijevic, Ivan and Przepiorka, Aneta and Pantic, Senka},
journal = {Reviews on advanced materials science},
pages = {1--5},
title = {{Novel strategies for neurotransmitter detection and measurement using advanced materials}},
volume = {42},
year = {2015}
}
@article{Jones1999,
abstract = {ErbB receptor activation is a complex process and is dependent upon the type and number of receptors expressed on a given cell. Previous studies with defined combinations of ErbB receptors expressed in mammalian cells have helped elucidate specific biological responses for many of the recognized gene products that serve as ligands for these receptors. However, no study has examined the binding of these ligands in a defined experimental system. To address this issue, the relative binding affinities of the egf domains of eleven ErbB ligands were measured on six ErbB receptor combinations using a soluble receptor-ligand binding format. The ErbB2/4 heterodimer was shown to bind all ligands tested with moderate to very high affinity. In contrast, ErbB3 showed much more restrictive ligand binding specificity and measurable binding was observed only with heregulin, neuregulin2$\beta$, epiregulin and the synthetic heregulin/egf chimera, biregulin. These studies also revealed that ErbB2 preferentially enhances ligand binding to ErbB3 or ErbB4 and to a lesser degree to ErbB1. Copyright (C) 1999 Federation of European Biochemical Societies.},
author = {Jones, Jennifer T. and Akita, Robert W. and Sliwkowski, Mark X.},
doi = {10.1016/S0014-5793(99)00283-5},
isbn = {0014-5793 (Print)$\backslash$n0014-5793 (Linking)},
issn = {00145793},
journal = {FEBS Letters},
keywords = {ErbB receptor and ligand,ErbB2-containing heterodimer,Neuregulin},
pmid = {10214951},
title = {{Binding specificities and affinities of egf domains for ErbB receptors}},
year = {1999}
}
@misc{Alm2003,
abstract = {Recent advances in high-throughput methods have provided us with a first glimpse of the overall structure of molecular interaction networks in biological systems. Ultimately, we expect that such information will change how we think about biological systems in a fundamental way. Instead of viewing the genetic parts list of an organism as a loose collection of biochemical activities, in the best case, we anticipate discrete networks of function to bridge the gap between genotype and phenotype, and to do so in a more profound way than the current qualitative classification of linked reactions into familiar pathways, such as glycolysis and the MAPK signal transduction cascades. At the present time, however, we are still far from a complete answer to the most basic question: what can we learn about biology by studying networks? Promising steps in this direction have come from such diverse approaches as mathematical analysis of global network structure, partitioning networks into functionally related modules and motifs, and even de novo design of networks. A complete picture will probably require integrating the data obtained from all of these approaches with modeling efforts at many different levels of detail.},
archivePrefix = {arXiv},
arxivId = {cond-mat/0202192v1},
author = {Alm, Eric and Arkin, Adam P.},
booktitle = {Current Opinion in Structural Biology},
doi = {10.1016/S0959-440X(03)00031-9},
eprint = {0202192v1},
file = {:Users/ozlem/Dropbox/papers/Biological Networks/1-s2.0-S0959440X03000319-main.pdf:pdf},
isbn = {0849385970},
issn = {0959440X},
pmid = {12727512},
primaryClass = {cond-mat},
title = {{Biological networks}},
year = {2003}
}
@article{Schaub2007,
abstract = {BACKGROUND:A central goal of Systems Biology is to model and analyze biological signaling pathways that interact with one another to form complex networks. Here we introduce Qualitative networks, an extension of Boolean networks. With this framework, we use formal verification methods to check whether a model is consistent with the laboratory experimental observations on which it is based. If the model does not conform to the data, we suggest a revised model and the new hypotheses are tested in-silico.RESULTS:We consider networks in which elements range over a small finite domain allowing more flexibility than Boolean values, and add target functions that allow to model a rich set of behaviors. We propose a symbolic algorithm for analyzing the steady state of these networks, allowing us to scale up to a system consisting of 144 elements and state spaces of approximately 1086 states. We illustrate the usefulness of this approach through a model of the interaction between the Notch and the Wnt signaling pathways in mammalian skin, and its extensive analysis.CONCLUSION:We introduce an approach for constructing computational models of biological systems that extends the framework of Boolean networks and uses formal verification methods for the analysis of the model. This approach can scale to multicellular models of complex pathways, and is therefore a useful tool for the analysis of complex biological systems. The hypotheses formulated during in-silico testing suggest new avenues to explore experimentally. Hence, this approach has the potential to efficiently complement experimental studies in biology},
author = {Schaub, Marc A. and Henzinger, Thomas A. and Fisher, Jasmin},
doi = {10.1186/1752-0509-1-4},
file = {:Users/ozlem/Desktop/Qualitative networks.pdf:pdf},
isbn = {1752-0509},
issn = {17520509},
journal = {BMC Systems Biology},
pmid = {17408511},
title = {{Qualitative networks: A symbolic approach to analyze biological signaling networks}},
year = {2007}
}
@article{Mund2011,
abstract = {The nuclear LSm2-8 (like Sm) complex and the cytoplasmic LSm1-7 complex play a central role in mRNA splicing and degradation, respectively. The LSm proteins are related to the spliceosomal Sm proteins that form a heteroheptameric ring around small nuclear RNA. The assembly process of the heptameric Sm complex is well established and involves several smaller Sm assembly intermediates. The assembly of the LSm complex, however, is less well studied. Here, we solved the 2.5 {\AA}-resolution structure of the LSm assembly intermediate that contains LSm5, LSm6, and LSm7. The three monomers display the canonical Sm fold and arrange into a hexameric LSm657-657 ring. We show that the order of the LSm proteins within the ring is consistent with the order of the related SmE, SmF, and SmG proteins in the heptameric Sm ring. Nonetheless, differences in RNA binding pockets prevent the prediction of the nucleotide binding preferences of the LSm complexes. Using high-resolution NMR spectroscopy, we confirm that LSm5, LSm6, and LSm7 also assemble into a 60-kDa hexameric ring in solution. With a combination of pull-down and NMR experiments, we show that the LSm657 complex can incorporate LSm23 in order to assemble further towards native LSm rings. Interestingly, we find that the NMR spectra of the LSm57, LSm657-657, and LSm23-657 complexes differ significantly, suggesting that the angles between the LSm building blocks change depending on the ring size of the complex. In summary, our results identify LSm657 as a plastic and functional building block on the assembly route towards the LSm1-7 and LSm2-8 complexes. {\textcopyright} 2011 Elsevier Ltd. All rights reserved.},
author = {Mund, Markus and Neu, Ancilla and Ullmann, Janina and Neu, Ursula and Sprangers, Remco},
doi = {10.1016/j.jmb.2011.09.051},
isbn = {1089-8638 (Electronic)$\backslash$n0022-2836 (Linking)},
issn = {00222836},
journal = {Journal of Molecular Biology},
keywords = {NMR spectroscopy,TROSY,mRNA degradation,mRNA splicing,macromolecular complexes},
number = {2},
pages = {165--176},
pmid = {22001694},
title = {{Structure of the LSm657 complex: An assembly intermediate of the LSm1-7 and LSm2-8 rings}},
volume = {414},
year = {2011}
}
@article{Stephens1998,
abstract = {Protein kinase B (PKB) is activated in response to phosphoinositide 3-kinases and their lipid products phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] and PtdIns(3,4)P2in the signaling pathways used by a wide variety of growth factors, antigens, and inflammatory stimuli. PKB is a direct target of these lipids, but this regulation is complex. The lipids can bind to the pleckstrin homologous domain of PKB, causing its translocation to the membrane, and also enable upstream, Thr308-directed kinases to phosphorylate and activate PKB. Four isoforms of these PKB kinases were purified from sheep brain. They bound PtdIns(3,4,5)P3and associated with lipid vesicles containing it. These kinases contain an NH2-terminal catalytic domain and a COOH-terminal pleckstrin homologous domain, and their heterologous expression augments receptor activation of PKB, which suggests they are the primary signal transducers that enable PtdIns(3,4,5)P3 or PtdIns- (3,4)P2 to activate PKB and hence to control signaling pathways regulating cell survival, glucose uptake, and glycogen metabolism.},
author = {Stephens, Len and Anderson, Karen and Stokoe, David and Erdjument-Bromage, Hediye and Painter, Gavin F and Holmes, Andrew B and Gaffney, Piers R J and Reese, Colin B and McCormick, Frank and Tempst, Paul and Coadwell, J and Hawkins, Phillip T},
doi = {10.1126/science.279.5351.710},
journal = {Science},
month = {jan},
number = {5351},
pages = {710 LP  -- 714},
title = {{Protein Kinase B Kinases That Mediate Phosphatidylinositol 3,4,5-Trisphosphate-Dependent Activation of Protein Kinase B}},
url = {http://science.sciencemag.org/content/279/5351/710.abstract},
volume = {279},
year = {1998}
}
@article{Earp2003,
abstract = {The EGF Receptor (EGFR), the first transmembrane receptor tyrosine kinase cloned and sequenced, and its closely related family members HER2, HER3, and HER4, play myriad roles in mammalian growth and development. Receptor activation involves ligand binding to separate receptors followed by formation of active dimers. These receptors can signal as homodimers or they can subtly alter signaling output by heterodimerizing with other family members. Adding complexity, these receptors with varying specificity bind at least 10 ligands from two ligand families, the EGF and neuregulin/heregulin families. This signaling system's impact on human neoplasia is underscored by the following: i.) EGFR is overexpressed or activated by autocrine or paracrine growth factor loops in at least 50{\%} of epithelial malignancies; ii.) HER2 is amplified and dramatically overexpressed in approximately 20{\%}-25{\%} or breast cancers; iii) HER3 and HER4 are variably expressed in breast and other cancers. Overexpression and/or activation of EGFR, HER2 and HER3 has been correlated with poor tumor prognosis; antibody and small molecule inhibitors of their activity are being tested as therapy in cancer patients. However, the signaling complexity engendered by four interacting receptors and ten ligands makes it difficult to definitively measure receptor signaling output in human tumors and even makes mechanistic studies of the family's role in normal physiology and neoplastic transformation a challenge. In spite of the literature's emphasis on growth control, activation by some EGF receptor family member ligands can produce tumor cell differentiation, characterized by growth cessation and differentiation gene product synthesis. The present work delineates a role for HER4 in breast cancer cell differentiation and demonstrates that HER4 is both necessary and sufficient to produce an anti-proliferative signal. These},
author = {Earp, H Shelton and Calvo, Benjamin F and Sartor, Carolyn I and An, With},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Earp et al. - 2003 - The EGF receptor family--multiple roles in proliferation, differentiation, and neoplasia with an emphasis on HER4.pdf:pdf},
isbn = {0065-7778 (Print)$\backslash$r0065-7778 (Linking)},
issn = {0065-7778},
journal = {Transactions of the American Clinical and Climatological Association},
pages = {315--333; discussion 333--334},
pmid = {12813928},
title = {{The EGF receptor family--multiple roles in proliferation, differentiation, and neoplasia with an emphasis on HER4.}},
volume = {114},
year = {2003}
}
@article{Kanehisa2016,
abstract = {KEGG (http://www.kegg.jp/ or http://www.genome.jp/ kegg/) is an integrated database resource for biolog-ical interpretation of genome sequences and other high-throughput data. Molecular functions of genes and proteins are associated with ortholog groups and stored in the KEGG Orthology (KO) database. The KEGG pathway maps, BRITE hierarchies and KEGG modules are developed as networks of KO nodes, representing high-level functions of the cell and the organism. Currently, more than 4000 com-plete genomes are annotated with KOs in the KEGG GENES database, which can be used as a refer-ence data set for KO assignment and subsequent reconstruction of KEGG pathways and other molec-ular networks. As an annotation resource, the fol-lowing improvements have been made. First, each KO record is re-examined and associated with pro-tein sequence data used in experiments of func-tional characterization. Second, the GENES database now includes viruses, plasmids, and the addendum category for functionally characterized proteins that are not represented in complete genomes. Third, new automatic annotation servers, BlastKOALA and GhostKOALA, are made available utilizing the non-redundant pangenome data set generated from the GENES database. As a resource for translational bioinformatics, various data sets are created for an-timicrobial resistance and drug interaction networks.},
author = {Kanehisa, Minoru and Sato, Yoko and Kawashima, Masayuki and Furumichi, Miho and Tanabe, Mao},
doi = {10.1093/nar/gkv1070},
isbn = {0305-1048},
issn = {13624962},
journal = {Nucleic Acids Research},
pmid = {26476454},
title = {{KEGG as a reference resource for gene and protein annotation}},
year = {2016}
}
@article{Colwill1999,
abstract = {Morphological changes during cell division in the yeast Saccharomyces cerevisiae are controlled by cell-cycle regulators. The Pcl-Pho85p kinase complex has been implicated in the regulation of the actin cytoskeleton at least in part through Rvs167p. Rvs167p consists of three domains called BAR, GPA, and SH3. Using a two-hybrid assay, we demonstrated that each region of Rvs167p participates in protein-protein interactions: the BAR domain bound the BAR domain of another Rvs167p protein and that of Rvs161p, the GPA region bound Pcl2p, and the SH3 domain bound Abp1p. We identified Rvs167p as a Las17p/Bee1p-interacting protein in a two-hybrid screen and showed that Las17p/Bee1p bound the SH3 domain of Rvs167p. We tested the extent to which the Rvs167p protein domains rescued phenotypes associated with deletion of RVS167: salt sensitivity, random budding, and endocytosis and sporulation defects. The BAR domain was sufficient for full or partial rescue of all rvs167 mutant phenotypes tested but not required for the sporulation defect for which the SH3 domain was also sufficient. Overexpression of Rvs167p inhibits cell growth. The BAR domain was essential for this inhibition and the SH3 domain had only a minor effect. Rvs167p may link the cell cycle regulator Pcl-Pho85p kinase and the actin cytoskeleton. We propose that Rvs167p is activated by phosphorylation in its GPA region by the Pcl-Pho85p kinase. Upon activation, Rvs167p enters a multiprotein complex, making critical contacts in its BAR domain and redundant or minor contacts with its SH3 domain.},
author = {Colwill, Karen and Field, Deborah and Moore, Lynda and Friesen, James and Andrews, Brenda},
isbn = {0016-6731 (Print)$\backslash$r0016-6731 (Linking)},
issn = {00166731},
journal = {Genetics},
number = {3},
pages = {881--893},
pmid = {10388809},
title = {{In vivo analysis of the domains of yeast Rvs167p suggests Rvs167p function is mediated through multiple protein interactions}},
volume = {152},
year = {1999}
}
@article{Sears2000,
abstract = {Our recent work has shown that activation of the Ras/Raf/ERK pathway extends the half-life of the Myc protein and thus enhances the accumulation of Myc activity. We have extended these observations by investigating two N-terminal phosphorylation sites in Myc, Thr 58 and Ser 62, which are known to be regulated by mitogen stimulation. We now show that the phosphorylation of these two residues is critical for determining the stability of Myc. Phosphorylation of Ser 62 is required for Ras-induced stabilization of Myc, likely mediated through the action of ERK. Conversely, phosphorylation of Thr 58, likely mediated by GSK-3 but dependent on the prior phosphorylation of Ser 62, is associated with degradation of Myc. Further analysis demonstrates that the Ras-dependent PI-3K pathway is also critical for controlling Myc protein accumulation, likely through the control of GSK-3 activity. These observations thus define a synergistic role for multiple Ras-mediated phosphorylation pathways in the control of Myc protein accumulation during the initial stage of cell proliferation.},
archivePrefix = {arXiv},
arxivId = {gr-qc/0208024},
author = {Sears, Rosalie and Nuckolls, Faison and Haura, Eric and Taya, Yoichi and Tamai, Katsuyuki and Nevins, Joseph R.},
doi = {10.1101/gad.836800},
eprint = {0208024},
isbn = {0890-9369 (Print)$\backslash$r0890-9369 (Linking)},
issn = {08909369},
journal = {Genes and Development},
keywords = {ERK,GSK-3,Myc,Ras,Ser 62,Stability,Thr 58},
pmid = {11018017},
primaryClass = {gr-qc},
title = {{Multiple Ras-dependent phosphorylation pathways regulate Myc protein stability}},
year = {2000}
}
@misc{Erkina2009,
abstract = {Cell response to stress at the transcriptional level is characterized by the rapid expression of a large set of genes. In yeast Saccharomyces cerevisiae this gene activation is determined by the action of two types of activators--HSF and partially redundant Msn2 and Msn4. While HSF activation mechanisms are relatively well established during the last decade, the mechanisms of regulation by Msn2/4 started to clarify only recently. Some of the important aspects of Msn2/4 regulation include nuclear-cytoplasmic shuttling and targeted degradation of these factors at gene promoters during transcription activation. These and other mechanisms will be discussed in the current review.},
author = {Erkina, T. Y. and Lavrova, M. V. and Erkine, A. M.},
booktitle = {Tsitologiya},
isbn = {0041-3771 (Print)$\backslash$r0041-3771 (Linking)},
issn = {00413771},
keywords = {Chromatin,HSF,Msn2,Msn4,Transcription},
number = {3},
pages = {271--278},
pmid = {19435282},
title = {{Alternative ways of stress regulation in cells of Saccharomyces cerevisiae: Transcriptional activators Msn2 and Msn4}},
volume = {51},
year = {2009}
}
@article{Sundquist2007,
abstract = {While recently developed short-read sequencing technologies may dramatically reduce the sequencing cost and eventually achieve the {\$}1000 goal for re-sequencing, their limitations prevent the de novo sequencing of eukaryotic genomes with the standard shotgun sequencing protocol. We present SHRAP (SHort Read Assembly Protocol), a sequencing protocol and assembly methodology that utilizes high-throughput short-read technologies. We describe a variation on hierarchical sequencing with two crucial differences: (1) we select a clone library from the genome randomly rather than as a tiling path and (2) we sample clones from the genome at high coverage and reads from the clones at low coverage. We assume that 200 bp read lengths with a 1{\%} error rate and inexpensive random fragment cloning on whole mammalian genomes is feasible. Our assembly methodology is based on first ordering the clones and subsequently performing read assembly in three stages: (1) local assemblies of regions significantly smaller than a clone size, (2) clone-sized assemblies of the results of stage 1, and (3) chromosome-sized assemblies. By aggressively localizing the assembly problem during the first stage, our method succeeds in assembling short, unpaired reads sampled from repetitive genomes. We tested our assembler using simulated reads from D. melanogaster and human chromosomes 1, 11, and 21, and produced assemblies with large sets of contiguous sequence and a misassembly rate comparable to other draft assemblies. Tested on D. melanogaster and the entire human genome, our clone-ordering method produces accurate maps, thereby localizing fragment assembly and enabling the parallelization of the subsequent steps of our pipeline. Thus, we have demonstrated that truly inexpensive de novo sequencing of mammalian genomes will soon be possible with high-throughput, short-read technologies using our methodology.},
author = {Sundquist, Andreas and Ronaghi, Mostafa and Tang, Haixu and Pevzner, Pavel and Batzoglou, Serafim},
doi = {10.1371/journal.pone.0000484},
isbn = {1932-6203},
issn = {19326203},
journal = {PLoS ONE},
number = {5},
pmid = {17534434},
title = {{Whole-genome sequencing and assembly with high-throughput, short-read technologies}},
volume = {2},
year = {2007}
}
@article{Buchel2013,
abstract = {BACKGROUND: Systems biology projects and omics technologies have led to a growing number of biochemical pathway models and reconstructions. However, the majority of these models are still created de novo, based on literature mining and the manual processing of pathway data.$\backslash$n$\backslash$nRESULTS: To increase the efficiency of model creation, the Path2Models project has automatically generated mathematical models from pathway representations using a suite of freely available software. Data sources include KEGG, BioCarta, MetaCyc and SABIO-RK. Depending on the source data, three types of models are provided: kinetic, logical and constraint-based. Models from over 2 600 organisms are encoded consistently in SBML, and are made freely available through BioModels Database at http://www.ebi.ac.uk/biomodels-main/path2models. Each model contains the list of participants, their interactions, the relevant mathematical constructs, and initial parameter values. Most models are also available as easy-to-understand graphical SBGN maps.$\backslash$n$\backslash$nCONCLUSIONS: To date, the project has resulted in more than 140 000 freely available models. Such a resource can tremendously accelerate the development of mathematical models by providing initial starting models for simulation and analysis, which can be subsequently curated and further parameterized.},
archivePrefix = {arXiv},
arxivId = {1307.7005},
author = {B{\"{u}}chel, Finja and Rodriguez, Nicolas and Swainston, Neil and Wrzodek, Clemens and Czauderna, Tobias and Keller, Roland and Mittag, Florian and Schubert, Michael and Glont, Mihai and Golebiewski, Martin and van Iersel, Martijn and Keating, Sarah and Rall, Matthias and Wybrow, Michael and Hermjakob, Henning and Hucka, Michael and Kell, Douglas B. and M{\"{u}}ller, Wolfgang and Mendes, Pedro and Zell, Andreas and Chaouiya, Claudine and Saez-Rodriguez, Julio and Schreiber, Falk and Laibe, Camille and Dr{\"{a}}ger, Andreas and {Le Nov{\`{e}}re}, Nicolas},
doi = {10.1186/1752-0509-7-116},
eprint = {1307.7005},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/B{\"{u}}chel et al. - 2013 - Path2Models Large-scale generation of computational models from biochemical pathway maps.pdf:pdf},
isbn = {1752-0509 (Electronic)$\backslash$r1752-0509 (Linking)},
issn = {17520509},
journal = {BMC Systems Biology},
keywords = {Constraint based models,Logical models,Modular rate law,SBGN,SBML},
pmid = {24180668},
title = {{Path2Models: Large-scale generation of computational models from biochemical pathway maps}},
volume = {7},
year = {2013}
}
@article{Page2002,
abstract = {TreeView provides a simple way to view the phylogenetic trees produced by a range of programs, such as PAUP*, PHYLIP, TREE-PUZZLE, and ClustalX. While some phylogenetic programs (such as the Macintosh version of PAUP*) have excellent tree printing facilities, many programs do not have the ability to generate publication quality trees. TreeView addresses this need. The program can read and write a range of tree file formats, display trees in a variety of styles, print trees, and save the tree as a graphic file. Protocols in this unit cover both displaying and printing a tree. Support protocols describe how to download and install TreeView, and how to display bootstrap values in trees generated by ClustalX and PAUP*.},
author = {Page, Roderic D M},
doi = {10.1002/0471250953.bi0602s01},
isbn = {1934-340X (Electronic)$\backslash$r1934-3396 (Linking)},
issn = {1934-340X},
journal = {Current protocols in bioinformatics / editoral board, Andreas D. Baxevanis ... [et al.]},
pages = {Unit 6.2},
pmid = {18792942},
title = {{Visualizing phylogenetic trees using TreeView.}},
volume = {Chapter 6},
year = {2002}
}
@article{Lindsay2009,
abstract = {Although the immune response is predominantly controlled at the transcriptional level, microRNA- mediated RNA interference is emerging as an important regulatory mechanism that operates at the translation level. Specifically, recent studies indicate that those miRNAs that are selectively and/or highly expressed in immune cells including the miR-17–92 cluster, miR-150, miR-155, miR-181 and miR-223 have a ‘permissive' function in the maturation, proliferation and differentiation of myeloid and lymphoid cells. Importantly, these actions of miRNAs often involve interactions with transcription factors. In contrast, the rapid and transient induction of miR-9, miR-146a and miR-155 has been speculated to negatively regulate the acute responses following activation of innate immune through},
author = {Lindsay, Eleni Tsitsiou and Mark A},
doi = {10.1016/j.coph.2009.05.003},
isbn = {1471-4892},
issn = {1471-4973},
journal = {Sponsored document from Current Opinion in Pharmacology},
number = {4},
pages = {514--520},
pmid = {19525145},
title = {{Current Opinion in Pharmacology}},
volume = {9},
year = {2009}
}
@article{Innocenti2003,
abstract = {lass I phosphoinositide 3-kinases (PI3Ks) are implicated in many cellular responses controlled by receptor tyrosine kinases (RTKs), including actin cytoskeletal remodeling. Within this pathway, Rac is a key downstream target/effector of PI3K. However, how the signal is routed from PI3K to Rac is unclear. One possible candidate for this function is the Rac-activating complex Eps8–Abi1–Sos-1, which possesses Rac-specific guanine nucleotide exchange factor (GEF) activity. Here, we show that Abi1 (also known as E3b1) recruits PI3K, via p85, into a multimolecular signaling complex that includes Eps8 and Sos-1. The recruit-ment of p85 to the Eps8–Abi1–Sos-1 complex and phos-C phatidylinositol 3, 4, 5 phosphate (PIP3), the catalytic product of PI3K, concur to unmask its Rac-GEF activity in vitro. Moreover, they are indispensable for the activation of Rac and Rac-dependent actin remodeling in vivo. On growth factor stimulation, endogenous p85 and Abi1 consistently colocalize into membrane ruffles, and cells lacking p85 fail to support Abi1-dependent Rac activation. Our results define a mechanism whereby propagation of signals, originating from RTKs or Ras and leading to actin reorgani-zation, is controlled by direct physical interaction between PI3K and a Rac-specific GEF complex.},
author = {Innocenti, Metello and Frittoli, Emanuela and Ponzanelli, Isabella and Falck, John R. and Brachmann, Saskia M. and {Di Fiore}, Pier Paolo and Scita, Giorgio},
doi = {10.1083/jcb.200206079},
isbn = {0021-9525 (Print)$\backslash$r0021-9525 (Linking)},
issn = {00219525},
journal = {Journal of Cell Biology},
keywords = {Actin remodeling,GEF,PI3K,RTK,Signaling},
pmid = {12515821},
title = {{Phosphoinositide 3-kinase activates Rac by entering in a complex with Eps8, Abi1, and Sos-1}},
year = {2003}
}
@article{Damm2001a,
abstract = {Telomerase, the ribonucleoprotein enzyme maintaining the telomeres of eukaryotic chromosomes, is active in most human cancers and in germline cells but, with few exceptions, not in normal human somatic tissues. Telomere maintenance is essential to the replicative potential of malignant cells and the inhibition of telomerase can lead to telomere shortening and cessation of unrestrained proliferation. We describe novel chemical compounds which selectively inhibit telomerase in vitro and in vivo. Treatment of cancer cells with these inhibitors leads to progressive telomere shortening, with no acute cytotoxicity, but a proliferation arrest after a characteristic lag period with hallmarks of senescence, including morphological, mitotic and chromosomal aberrations and altered patterns of gene expression. Telomerase inhibition and telomere shortening also result in a marked reduction of the tumorigenic potential of drug-treated tumour cells in a mouse xenograft model. This model was also used to demonstrate in vivo efficacy with no adverse side effects and uncomplicated oral administration of the inhibitor. These findings indicate that potent and selective, non-nucleosidic telomerase inhibitors can be designed as novel cancer treatment modalities.},
author = {Damm, Klaus and Hemmann, Ulrike and Garin-Chesa, Pilar and Hauel, Norbert and Kauffmann, Iris and Priepke, Henning and Niestroj, Claudia and Daiber, Christine and Enenkel, Barbara and Guilliard, Bernd and Lauritsch, Ines and M??ller, Elfriede and Pascolo, Emanuelle and Sauter, Gabriele and Pantic, Milena and Martens, Uwe M. and Wenz, Christian and Lingner, Joachim and Kraut, Norbert and Rettig, Wolfgang J. and Schnapp, Andreas},
doi = {10.1093/emboj/20.24.6958},
isbn = {0261-4189 (Print)$\backslash$r0261-4189 (Linking)},
issn = {02614189},
journal = {EMBO Journal},
keywords = {Cancer,Inhibitor,Microarray,Senescence,Telomerase},
number = {24},
pages = {6958--6968},
pmid = {11742973},
title = {{A highly selective telomerase inhibitor limiting human cancer cell proliferation}},
volume = {20},
year = {2001}
}
@article{Heath2009,
abstract = {Systems biology is a broad field that incorporates both computational and experimental approaches to provide a system level understanding of biological function. Initial forays into computational systems biology have focused on a variety of biological networks such as protein-protein interaction, signaling, transcription and metabolic networks. In this review we will provide an overview of available data relevant to systems biology, properties of biological networks, algorithms to compare and align networks and simulation and modeling techniques. Looking towards the future, we will discuss work on integrating additional functional information with biological networks, such as three dimensional structures and the complex environment of the cell. Combining and understanding this information requires development of novel algorithms and data integration techniques and solving these difficult computational problems will advance both computational and biological research. {\textcopyright} 2009 Elsevier Inc. All rights reserved.},
author = {Heath, Allison P. and Kavraki, Lydia E.},
doi = {10.1016/j.cosrev.2009.01.002},
isbn = {1574-0137},
issn = {15740137},
journal = {Computer Science Review},
title = {{Computational challenges in systems biology}},
year = {2009}
}
@article{Julien2013,
abstract = {HIV-1 entry into CD4(+) target cells is mediated by cleaved envelope glycoprotein (Env) trimers that have been challenging to characterize structurally. Here, we describe the crystal structure at 4.7 angstroms of a soluble, cleaved Env trimer that is stabilized and antigenically near-native (termed the BG505 SOSIP.664 gp140 trimer) in complex with a potent broadly neutralizing antibody, PGT122. The structure shows a prefusion state of gp41, the interaction between the component gp120 and gp41 subunits, and how a close association between the gp120 V1/V2/V3 loops stabilizes the trimer apex around the threefold axis. The complete epitope of PGT122 on the trimer involves gp120 V1, V3, and several surrounding glycans. This trimer structure advances our understanding of how Env functions and is presented to the immune system, and provides a blueprint for structure-based vaccine design.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Julien, J.-P. and Cupo, A. and Sok, D. and Stanfield, R. L. and Lyumkis, D. and Deller, M. C. and Klasse, P.-J. and Burton, D. R. and Sanders, R. W. and Moore, J. P. and Ward, A. B. and Wilson, I. A.},
doi = {10.1126/science.1245625},
eprint = {NIHMS150003},
isbn = {0036-8075},
issn = {0036-8075},
journal = {Science},
number = {6165},
pages = {1477--1483},
pmid = {24179159},
title = {{Crystal Structure of a Soluble Cleaved HIV-1 Envelope Trimer}},
url = {http://www.sciencemag.org/cgi/doi/10.1126/science.1245625},
volume = {342},
year = {2013}
}
@article{Martignetti2016,
abstract = {In many analyses of high-throughput data in systems biology, there is a need to quantify the activity of a set of genes in individual samples. A typical example is the case where it is necessary to estimate the activity of a transcription factor (which is often not directly measurable) from the expression of its target genes. We present here ROMA (Representation and quantification Of Module Activities) Java software, designed for fast and robust computation of the activity of gene sets (or modules) with coordinated expression. ROMA activity quantification is based on the simplest uni-factor linear model of gene regulation that approximates the expression data of a gene set by its first principal component. The proposed algorithm implements novel functionalities: it provides several method modifications for principal components computation, including weighted, robust and centered methods; it distinguishes overdispersed modules (based on the variance explained by the first principal component) and coordinated modules (based on the significance of the spectral gap); finally, it computes statistical significance of the estimated module overdispersion or coordination. ROMA can be applied in many contexts, from estimating differential activities of transcriptional factors to finding overdispersed pathways in single-cell transcriptomics data. We describe here the principles of ROMA providing several practical examples of its use. ROMA source code is available at https://github.com/sysbio-curie/Roma.},
author = {Martignetti, Loredana and Calzone, Laurence and Bonnet, Eric and Barillot, Emmanuel and Zinovyev, Andrei},
doi = {10.3389/fgene.2016.00018},
isbn = {1664-8021 (Electronic)
1664-8021 (Linking)},
issn = {16648021},
journal = {Frontiers in Genetics},
keywords = {Coordinated pathway,Gene expression,Gene set,Module activity,Overdispersed pathway,Proteomics,Transcription factors},
pmid = {26925094},
title = {{ROMA: Representation and quantification of module activity from target expression data}},
year = {2016}
}
@article{Kuscu2014,
abstract = {RNA-guided genome editing with the CRISPR-Cas9 system has great potential for basic and clinical research, but the determinants of targeting specificity and the extent of off-target cleavage remain insufficiently understood. Using chromatin immunoprecipitation and high-throughput sequencing (ChIP-seq), we mapped genome-wide binding sites of catalytically inactive Cas9 (dCas9) in HEK293T cells, in combination with 12 different single guide RNAs (sgRNAs). The number of off-target sites bound by dCas9 varied from approximately 10 to {\textgreater}1,000 depending on the sgRNA. Analysis of off-target binding sites showed the importance of the PAM-proximal region of the sgRNA guiding sequence and that dCas9 binding sites are enriched in open chromatin regions. When targeted with catalytically active Cas9, some off-target binding sites had indels above background levels in a region around the ChIP-seq peak, but generally at lower rates than the on-target sites. Our results elucidate major determinants of Cas9 targeting, and we show that ChIP-seq allows unbiased detection of Cas9 binding sites genome-wide.},
author = {Kuscu, Cem and Arslan, Sevki and Singh, Ritambhara and Thorpe, Jeremy and Adli, Mazhar},
doi = {10.1038/nbt.2916},
isbn = {1546-1696 (Electronic)$\backslash$r1087-0156 (Linking)},
issn = {1087-0156},
journal = {Nature Biotechnology},
number = {7},
pages = {677--683},
pmid = {24837660},
title = {{Genome-wide analysis reveals characteristics of off-target sites bound by the Cas9 endonuclease}},
url = {http://www.nature.com/doifinder/10.1038/nbt.2916},
volume = {32},
year = {2014}
}
@incollection{Kuzmin2014,
abstract = {Genetic interactions occur when mutant alleles of two or more genes collaborate to generate an unusual composite phenotype, one that would not be predicted based on the expected combined effects of the individual mutant alleles. Synthetic Genetic Array (SGA) methodology was developed to automate yeast genetic analysis and enable systematic genetic interaction studies. In its simplest form, SGA consists of a series of replica pinning steps, which enable the construction of haploid double mutants through mating and meiotic recombination. For example, a strain carrying a query mutation, such as a deletion allele of a nonessential gene or a conditional temperature sensitive allele of an essential gene, could be crossed to an input array of yeast mutants, such as the complete set of {\~{}}5,000 viable deletion mutants, to generate an output array of double mutants, that can be scored for genetic interactions based on estimates of cellular fitness derived from colony-size measurements. A simple quantitative measure of genetic interactions can be derived from colony size, which serves as a proxy for fitness. Furthermore, SGA can be applied in a variety of other contexts, such as Synthetic Dosage Lethality (SDL), in which a query mutation is crossed into an array of yeast strains, each of which overexpresses a different gene, thus making use of SGA to probe for gain-of-function phenotypes in specific genetic backgrounds. High-Content Screening (HCS) also integrates SGA to perform genome-wide screens for quantitative analysis of morphological phenotypes or pathway activity based upon fluorescent markers, extending genetic interaction analysis beyond fitness-based measurements. Genetic interaction studies offer insight into gene function, pathway structure, and buffering, and thus a complete genetic interaction network of yeast will generate a global functional wiring diagram for a eukaryotic cell.},
author = {Kuzmin, Elena and Sharifpoor, Sara and Baryshnikova, Anastasia and Costanzo, Michael and Myers, Chad L and Andrews, Brenda J and Boone, Charles},
booktitle = {Methods in molecular biology (Clifton, N.J.)},
doi = {10.1007/978-1-4939-1363-3_10},
isbn = {978-1-4939-1362-6},
issn = {1940-6029},
pages = {143--68},
pmid = {25213244},
title = {{Synthetic genetic array analysis for global mapping of genetic networks in yeast.}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/25213244},
volume = {1205},
year = {2014}
}
@article{Hsu2013,
abstract = {The Streptococcus pyogenes Cas9 (SpCas9) nuclease can be efficiently targeted to genomic loci by means of single-guide RNAs (sgRNAs) to enable genome editing. Here, we characterize SpCas9 targeting specificity in human cells to inform the selection of target sites and avoid off-target effects. Our study evaluates {\textgreater}700 guide RNA variants and SpCas9-induced indel mutation levels at {\textgreater}100 predicted genomic off-target loci in 293T and 293FT cells. We find that SpCas9 tolerates mismatches between guide RNA and target DNA at different positions in a sequence-dependent manner, sensitive to the number, position and distribution of mismatches. We also show that SpCas9-mediated cleavage is unaffected by DNA methylation and that the dosage of SpCas9 and sgRNA can be titrated to minimize off-target modification. To facilitate mammalian genome engineering applications, we provide a web-based software tool to guide the selection and validation of target sequences as well as off-target analyses.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Hsu, Patrick D and Scott, David A and Weinstein, Joshua A and Ran, F Ann and Konermann, Silvana and Agarwala, Vineeta and Li, Yinqing and Fine, Eli J and Wu, Xuebing and Shalem, Ophir and Cradick, Thomas J and Marraffini, Luciano A and Bao, Gang and Zhang, Feng},
doi = {10.1038/nbt.2647},
eprint = {NIHMS150003},
isbn = {1095-9203 (Electronic)$\backslash$r0036-8075 (Linking)},
issn = {1087-0156},
journal = {Nature Biotechnology},
number = {9},
pages = {827--832},
pmid = {23873081},
title = {{DNA targeting specificity of RNA-guided Cas9 nucleases}},
url = {http://www.nature.com/doifinder/10.1038/nbt.2647},
volume = {31},
year = {2013}
}
@article{Fisher2004,
abstract = {Nudix hydrolases form a protein family whose function is to hydrolyse intracellular nucleotides and so regulate their levels and eliminate potentially toxic derivatives. The genome of the radioresistant bacterium Deinococcus radiodurans encodes 25 nudix hydrolases, an unexpectedly large number. These may contribute to radioresistance by removing mutagenic oxidised and otherwise damaged nucleotides. Characterisation of these hydrolases is necessary to understand the reason for their presence. Here, we report the cloning and characterisation of the DR0975 gene product, a nudix hydrolase that appears to be unique to this organism.},
author = {Fisher, David I. and Cartwright, Jared L. and Harashima, Hideyoshi and Kamiya, Hiroyuki and McLennan, Alexander G.},
doi = {10.1186/1471-2091-5-7},
isbn = {1471-2091 (Electronic)$\backslash$r1471-2091 (Linking)},
issn = {14712091},
journal = {BMC Biochemistry},
pages = {1--24},
pmid = {15147580},
title = {{Characterization of a Nudix hydrolase from Deinococcus radiodurans with a marked specificity for (deoxy)ribonucleoside 5′-diphosphates}},
volume = {5},
year = {2004}
}
@article{Novere2009,
abstract = {Circuit diagrams and Unified Modeling Language diagrams are just two examples of standard visual languages that help accelerate work by promoting regularity, removing ambiguity and enabling software tool support for communication of complex information. Ironically, despite having one of the highest ratios of graphical to textual information, biology still lacks standard graphical notations. The recent deluge of biological knowledge makes addressing this deficit a pressing concern. Toward this goal, we present the Systems Biology Graphical Notation (SBGN), a visual language developed by a community of biochemists, modelers and computer scientists. SBGN consists of three complementary languages: process diagram, entity relationship diagram and activity flow diagram. Together they enable scientists to represent networks of biochemical interactions in a standard, unambiguous way. We believe that SBGN will foster efficient and accurate representation, visualization, storage, exchange and reuse of information on all kinds of biological knowledge, from gene regulation, to metabolism, to cellular signaling. “Un},
author = {Nov{\`{e}}re, Nicolas Le and Hucka, Michael and Mi, Huaiyu and Moodie, Stuart and Schreiber, Falk and Sorokin, Anatoly and Demir, Emek and Wegner, Katja and Aladjem, Mirit I and Wimalaratne, Sarala M and Bergman, Frank T and Gauges, Ralph and Ghazal, Peter and Kawaji, Hideya and Li, Lu and Matsuoka, Yukiko and Vill{\'{e}}ger, Alice and Boyd, Sarah E and Jouraku, Akiya and Kim, Sohyoung and Kolpakov, Fedor and Luna, Augustin and Sahle, Sven and Schmidt, Esther},
doi = {10.1038/nbt1558},
file = {:Users/ozlem/Desktop/papers/Disease Map Papers/nbt.1558.pdf:pdf},
isbn = {1087-0156},
journal = {Nature biotechnology},
number = {8},
pages = {735--742},
title = {{The Systems Biology Graphical Notation : Abstract : Nature Biotechnology}},
url = {http://www.nature.com/nbt/journal/v27/n8/abs/nbt.1558.html},
volume = {27},
year = {2009}
}
@article{Song2013,
abstract = {RNA decapping is an important contributor to gene expression and is a critical determinant of mRNA decay. The recent demonstration that mammalian cells harbor at least two distinct decapping enzymes that preferentially modulate a subset of mRNAs raises the intriguing possibility of whether additional decapping enzymes exist. Because both known decapping proteins, Dcp2 and Nudt16, are members of the Nudix hydrolase family, we set out to determine whether other members of this family of proteins also contain intrinsic RNA decapping activity. Here we demonstrate that six additional mouse Nudix proteins--Nudt2, Nudt3, Nudt12, Nudt15, Nudt17, and Nudt19--have varying degrees of decapping activity in vitro on both monomethylated and unmethylated capped RNAs. The decapping products from Nudt17 and Nudt19 were analogous to Dcp2 and predominantly generated m⁷GDP, while cleavage by Nudt2, Nudt3, Nudt12, and Nudt15 was more pleiotropic and generated both m⁷GMP and m⁷GDP. Interestingly, all six Nudix proteins as well as both Dcp2 and Nudt16 could hydrolyze the cap of an unmethylated capped RNA, indicating that decapping enzymes may be less constrained for the presence of the methyl moiety. Investigation of Saccharomyces cerevisiae Nudix proteins revealed that the yeast homolog of Nudt3, Ddp1p, also possesses decapping activity in vitro. Moreover, the bacterial Nudix pyrophosphohydrolase RppH displayed RNA decapping activity and released m⁷GDP product comparable to Dcp2, indicating that decapping is an evolutionarily conserved activity that preceded mammalian cap formation. These findings demonstrate that multiple Nudix family hydrolases may function in mRNA decapping and mRNA stability.},
author = {Song, M.-G. and Bail, S. and Kiledjian, M.},
doi = {10.1261/rna.037309.112},
isbn = {1469-9001 (Electronic)$\backslash$n1355-8382 (Linking)},
issn = {1355-8382},
journal = {RNA},
number = {3},
pages = {390--399},
pmid = {23353937},
title = {{Multiple Nudix family proteins possess mRNA decapping activity}},
url = {http://rnajournal.cshlp.org/cgi/doi/10.1261/rna.037309.112},
volume = {19},
year = {2013}
}
@misc{Zerbino2010,
abstract = {The Velvet de novo assembler was designed to build contigs and eventually scaffolds from short-read sequencing data. This protocol describes how to use Velvet, interpret its output, and tune its parameters for optimal results. It also covers practical issues such as configuration, using the VelvetOptimiser routine, and processing colorspace data.},
author = {Zerbino, Daniel R.},
booktitle = {Current Protocols in Bioinformatics},
doi = {10.1002/0471250953.bi1105s31},
isbn = {0471250953},
issn = {19343396},
keywords = {Genome assembly,Next-Generation Sequencing,de Bruijn Graphs},
number = {SUPPL. 31},
pmid = {20836074},
title = {{Using the Velvet de novo assembler for short-read sequencing technologies}},
year = {2010}
}
@article{Gustafsson2014,
abstract = {Many common diseases, such as asthma, diabetes or obesity, involve altered interactions between thousands of genes. High-throughput techniques (omics) allow identification of such genes and their products, but functional understanding is a formidable challenge. Network-based analyses of omics data have identified modules of disease-associated genes that have been used to obtain both a systems level and a molecular understanding of disease mechanisms. For example, in allergy a module was used to find a novel candidate gene that was validated by functional and clinical studies. Such analyses play important roles in systems medicine. This is an emerging discipline that aims to gain a translational understanding of the complex mechanisms underlying common diseases. In this review, we will explain and provide examples of how network-based analyses of omics data, in combination with functional and clinical studies, are aiding our understanding of disease, as well as helping to prioritize diagnostic markers or therapeutic candidate genes. Such analyses involve significant problems and limitations, which will be discussed. We also highlight the steps needed for clinical implementation.},
author = {Gustafsson, Mika and Nestor, Colm E. and Zhang, Huan and Barab{\'{a}}si, Albert L{\'{a}}szl{\'{o}} and Baranzini, Sergio and Brunak, S{\"{o}}ren and Chung, Kian F. and Federoff, Howard J. and Gavin, Anne Claude and Meehan, Richard R. and Picotti, Paola and Pujana, Miguel {\`{A}}ngel and Rajewsky, Nikolaus and Smith, Kenneth G.C. and Sterk, Peter J. and Villoslada, Pablo and Benson, Mikael},
doi = {10.1186/s13073-014-0082-6},
file = {:Users/ozlem/Desktop/papers/Disease Map Papers/13073{\_}2014{\_}Article{\_}82.pdf:pdf},
isbn = {1756-994x},
issn = {1756994X},
journal = {Genome Medicine},
number = {10},
pages = {1--11},
pmid = {25473422},
title = {{Modules, networks and systems medicine for understanding disease and aiding diagnosis}},
volume = {6},
year = {2014}
}
@article{Naldi2009,
abstract = {Many important problems in cell biology require the consideration of dense nonlinear interactions between functional modules. The requirement of computer simulation for the understanding of cellular processes is now widely accepted, and a variety of modelling frameworks have been designed to meet this need. Here, we present a novel public release of the Gene Interaction Network simulation suite (GINsim), a software designed for the qualitative modelling and analysis of regulatory networks. The main functionalities of GINsim are illustrated through the analysis of a logical model for the core network controlling the fission yeast cell cycle. The last public release of GINsim (version 2.3), as well as development versions, can be downloaded from the dedicated website (http://gin.univ-mrs.fr/GINsim/), which further includes a model library, along with detailed tutorial and user manual. {\textcopyright} 2009 Elsevier Ireland Ltd. All rights reserved.},
author = {Naldi, A. and Berenguier, D. and Faur{\'{e}}, A. and Lopez, F. and Thieffry, D. and Chaouiya, C.},
doi = {10.1016/j.biosystems.2009.04.008},
file = {:Users/ozlem/Desktop/Tools/1-s2.0-S0303264709000665-main.pdf:pdf},
issn = {03032647},
journal = {Biosystems},
keywords = {Computational systems biology,Dynamical simulation,Logical modelling,Regulatory networks},
month = {aug},
number = {2},
pages = {134--139},
pmid = {19426782},
title = {{Logical modelling of regulatory networks with GINsim 2.3}},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0303264709000665},
volume = {97},
year = {2009}
}
@misc{Merico2009,
abstract = {Networks in biology can appear complex and difficult to decipher. We illustrate how to interpret biological networks with the help of frequently used visualization and analysis patterns.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Merico, Daniele and Gfeller, David and Bader, Gary D.},
booktitle = {Nature Biotechnology},
doi = {10.1038/nbt.1567},
eprint = {NIHMS150003},
isbn = {1546-1696 (Electronic)$\backslash$r1087-0156 (Linking)},
issn = {10870156},
pmid = {19816451},
title = {{How to visually interpret biological data using networks}},
year = {2009}
}
@article{Roux2004,
abstract = {Conserved signaling pathways that activate the mitogen-activated protein kinases (MAPKs) are involved in relaying extracellular stimulations to intracellular responses. The MAPKs coordinately regulate cell proliferation, differentiation, motility, and survival, which are functions also known to be mediated by members of a growing family of MAPK-activated protein kinases (MKs; formerly known as MAPKAP kinases). The MKs are related serine/threonine kinases that respond to mitogenic and stress stimuli through proline-directed phosphorylation and activation of the kinase domain by extracellular signal-regulated kinases 1 and 2 and p38 MAPKs. There are currently 11 vertebrate MKs in five subfamilies based on primary sequence homology: the ribosomal S6 kinases, the mitogen- and stress-activated kinases, the MAPK-interacting kinases, MAPK-activated protein kinases 2 and 3, and MK5. In the last 5 years, several MK substrates have been identified, which has helped tremendously to identify the biological role of the members of this family. Together with data from the study of MK-knockout mice, the identities of the MK substrates indicate that they play important roles in diverse biological processes, including mRNA translation, cell proliferation and survival, and the nuclear genomic response to mitogens and cellular stresses. In this article, we review the existing data on the MKs and discuss their physiological functions based on recent discoveries.},
author = {Roux, P. P. and Blenis, J.},
doi = {10.1128/MMBR.68.2.320-344.2004},
isbn = {1092-2172$\backslash$r1098-5557},
issn = {1092-2172},
journal = {Microbiology and Molecular Biology Reviews},
pmid = {15187187},
title = {{ERK and p38 MAPK-Activated Protein Kinases: a Family of Protein Kinases with Diverse Biological Functions}},
year = {2004}
}
@article{Kanehisa2016a,
abstract = {KEGG (http://www.kegg.jp/ or http://www.genome.jp/ kegg/) is an integrated database resource for biolog-ical interpretation of genome sequences and other high-throughput data. Molecular functions of genes and proteins are associated with ortholog groups and stored in the KEGG Orthology (KO) database. The KEGG pathway maps, BRITE hierarchies and KEGG modules are developed as networks of KO nodes, representing high-level functions of the cell and the organism. Currently, more than 4000 com-plete genomes are annotated with KOs in the KEGG GENES database, which can be used as a refer-ence data set for KO assignment and subsequent reconstruction of KEGG pathways and other molec-ular networks. As an annotation resource, the fol-lowing improvements have been made. First, each KO record is re-examined and associated with pro-tein sequence data used in experiments of func-tional characterization. Second, the GENES database now includes viruses, plasmids, and the addendum category for functionally characterized proteins that are not represented in complete genomes. Third, new automatic annotation servers, BlastKOALA and GhostKOALA, are made available utilizing the non-redundant pangenome data set generated from the GENES database. As a resource for translational bioinformatics, various data sets are created for an-timicrobial resistance and drug interaction networks.},
author = {Kanehisa, Minoru and Sato, Yoko and Kawashima, Masayuki and Furumichi, Miho and Tanabe, Mao},
doi = {10.1093/nar/gkv1070},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Kanehisa et al. - 2016 - KEGG as a reference resource for gene and protein annotation(2).pdf:pdf},
isbn = {0305-1048},
issn = {13624962},
journal = {Nucleic Acids Research},
pmid = {26476454},
title = {{KEGG as a reference resource for gene and protein annotation}},
year = {2016}
}
@article{Tee2002,
abstract = {Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder that occurs upon mutation of either the TSC1 or TSC2 genes, which encode the protein products hamartin and tuberin, respectively. Here, we show that hamartin and tuberin function together to inhibit mammalian target of rapamycin (mTOR)-mediated signaling to eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase 1 (S6K1). First, coexpression of hamartin and tuberin repressed phosphorylation of 4E-BP1, resulting in increased association of 4E-BP1 with eIF4E; importantly, a mutant of TSC2 derived from TSC patients was defective in repressing phosphorylation of 4E-BP1. Second, the activity of S6K1 was repressed by coexpression of hamartin and tuberin, but the activity of rapamycin-resistant mutants of S6K1 were not affected, implicating mTOR in the TSC-mediated inhibitory effect on S6K1. Third, hamartin and tuberin blocked the ability of amino acids to activate S6K1 within nutrient-deprived cells, a process that is dependent on mTOR. These findings strongly implicate the tuberin-hamartin tumor suppressor complex as an inhibitor of mTOR and suggest that the formation of tumors within TSC patients may result from aberrantly high levels of mTOR-mediated signaling to downstream targets. mTOR,mammalian target of rapamycin;TSC,tuberous sclerosis complex;PI3K,phosphoinositide-3-kinase;S6K1,ribosomal protein S6 kinase 1;4E-BP1,eIF4E-binding protein;HEK,human embryonic kidney;HA,hemagglutinin},
author = {Tee, Andrew R and Fingar, Diane C and Manning, Brendan D and Kwiatkowski, David J and Cantley, Lewis C and Blenis, John},
doi = {10.1073/pnas.202476899},
journal = {Proceedings of the National Academy of Sciences},
month = {oct},
number = {21},
pages = {13571 LP  -- 13576},
title = {{Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling}},
url = {http://www.pnas.org/content/99/21/13571.abstract},
volume = {99},
year = {2002}
}
@article{Casamayor1999,
abstract = {3-phosphoinositide-dependent protein kinase-1 (PDK1) expressed in unstimulated 293 cells was phosphorylated at Ser-25, Ser-241, Ser-393, Ser-396 and Ser-410 and the level of phosphorylation of each site was unaffected by stimulation with insulin-like growth factor-1. Mutation of Ser-241 to Ala abolished PDK1 activity, whereas mutation of the other phosphorylation sites individually to Ala did not affect PDK1 activity. Ser-241, unlike the other phosphorylation sites on PDK1, was resistant to dephosphorylation by protein phosphatase 2A(1). Ser-241 lies in the activation loop of the PDK1 kinase domain between subdomains VII and VIII in the equivalent position to the site that PDK1 phosphorylates on its protein kinase substrates. PDK1 expressed in bacteria was active and phosphorylated at Ser-241, suggesting that PDK1 can phosphorylate itself at this site, leading to its own activation.},
author = {Casamayor, A and Morrice, N and Alessi, Dario R},
doi = {10.1042/0264-6021:3420287},
isbn = {0264-6021 (Print)$\backslash$n0264-6021 (Linking)},
issn = {0264-6021},
journal = {Biochemical J.},
keywords = {Amino Acid Sequence,Binding Sites,Binding Sites: genetics,Cell Line,Enzyme Activation,Escherichia coli,Escherichia coli: genetics,Humans,Molecular Sequence Data,Mutagenesis, Site-Directed,Peptide Mapping,Phosphorylation,Protein-Serine-Threonine Kinases,Protein-Serine-Threonine Kinases: chemistry,Protein-Serine-Threonine Kinases: genetics,Protein-Serine-Threonine Kinases: metabolism,Recombinant Fusion Proteins,Recombinant Fusion Proteins: chemistry,Recombinant Fusion Proteins: genetics,Recombinant Fusion Proteins: metabolism,Sequence Homology, Amino Acid,Serine,Serine: chemistry,Transfection},
pmid = {10455013},
title = {{Phosphorylation of Ser-241 is essential for the activity of 3-phosphoinositide-dependent protein kinase-1: identification of five sites of phosphorylation in vivo.}},
year = {1999}
}
@article{Wrzodek2013,
abstract = {BACKGROUND: The KEGG PATHWAY database provides a plethora of pathways for a diversity of organisms. All pathway components are directly linked to other KEGG databases, such as KEGG COMPOUND or KEGG REACTION. Therefore, the pathways can be extended with an enormous amount of information and provide a foundation for initial structural modeling approaches. As a drawback, KGML-formatted KEGG pathways are primarily designed for visualization purposes and often omit important details for the sake of a clear arrangement of its entries. Thus, a direct conversion into systems biology models would produce incomplete and erroneous models.$\backslash$n$\backslash$nRESULTS: Here, we present a precise method for processing and converting KEGG pathways into initial metabolic and signaling models encoded in the standardized community pathway formats SBML (Levels 2 and 3) and BioPAX (Levels 2 and 3). This method involves correcting invalid or incomplete KGML content, creating complete and valid stoichiometric reactions, translating relations to signaling models and augmenting the pathway content with various information, such as cross-references to Entrez Gene, OMIM, UniProt ChEBI, and many more.Finally, we compare several existing conversion tools for KEGG pathways and show that the conversion from KEGG to BioPAX does not involve a loss of information, whilst lossless translations to SBML can only be performed using SBML Level 3, including its recently proposed qualitative models and groups extension packages.$\backslash$n$\backslash$nCONCLUSIONS: Building correct BioPAX and SBML signaling models from the KEGG database is a unique characteristic of the proposed method. Further, there is no other approach that is able to appropriately construct metabolic models from KEGG pathways, including correct reactions with stoichiometry. The resulting initial models, which contain valid and comprehensive SBML or BioPAX code and a multitude of cross-references, lay the foundation to facilitate further modeling steps.},
author = {Wrzodek, Clemens and B{\"{u}}chel, Finja and Ruff, Manuel and Dr{\"{a}}ger, Andreas and Zell, Andreas},
doi = {10.1186/1752-0509-7-15},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Wrzodek et al. - 2013 - Precise generation of systems biology models from KEGG pathways(2).pdf:pdf},
isbn = {1752-0509 (Electronic)$\backslash$r1752-0509 (Linking)},
issn = {17520509},
journal = {BMC Systems Biology},
keywords = {BioPAX,Comparison,Converter,KEGG,KGML,Modeling,Qualitative modeling,Quantitative modeling,SBML,Systems biology},
pmid = {23433509},
title = {{Precise generation of systems biology models from KEGG pathways}},
year = {2013}
}
@article{Tang1999,
abstract = {The FKHR gene was first identified from its disruption by the t(2;13) chromosomal translocation seen in the pediatric tumor alveolar rhabdomyosarcoma. It encodes for a member of the forkhead family of transcription factors. Recently, a homolog of FKHR in the nematode Caenorhabditis elegans was identified called DAF-16, which is a downstream target of two Akt homologs in an insulin-related signaling pathway. We have examined the possible role of Akt in the regulation of FKHR. We find that FKHR can bind in vitro to the insulin-responsive sequence (IRS) in the insulin-like growth factor-binding protein 1 promoter and can activate transcription from a reporter plasmid containing multiple copies of the IRS. Expression of active but not inactive Akt can suppress FKHR-mediated transcriptional activation. Akt can phosphorylate FKHR in vitro on three phosphoacceptor sites, at least a subset of which can also be phosphorylated by Akt in vivo. Importantly, mutation of these three sites to alanine residues enhances the transcriptional activity of FKHR and renders it resistant to inhibition by Akt. Expression of an Akt-resistant mutant of FKHR causes apoptosis in 293T cells in a manner dependent on DNA binding. These results suggest that FKHR may be a direct nuclear regulatory target for Akt in both metabolic and cell survival pathways.},
author = {Tang, Eric D. and Nu{\~{n}}ez, Gabriel and Barr, Frederic G. and Guan, Kun Liang},
doi = {10.1074/jbc.274.24.16741},
isbn = {0021-9258 (Print)$\backslash$r0021-9258 (Linking)},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {10358014},
title = {{Negative regulation of the forkhead transcription factor FKHR by Akt}},
year = {1999}
}
@article{Mussel2010,
author = {M{\"{u}}ssel, Christoph and Hopfensitz, Martin and Kestler, Hans},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/M{\"{u}}ssel, Hopfensitz, Kestler - 2010 - BoolNet package vignette.pdf:pdf},
journal = {Tutorial},
pages = {1--34},
title = {{BoolNet package vignette}},
year = {2010}
}
@article{Tong2004,
abstract = {A genetic interaction network containing?1000 genes and?4000 interactions was mapped by crossing mutations in 132 different query genes into a set of ?4700 viable gene yeast deletion mutants and scoring the double mutant progeny for fitness defects.Network connectivity was predictive of function because interactions often occurred among functionally related genes, and similar patterns of interactions tended to identify components of the same pathway.The genetic network exhibited dense local neighborhoods; therefore, the position of a gene on a partially mapped network is predictive of other genetic interactions.Because digenic interactions are common in yeast, similar networks may underlie the complex genetics associated with inherited phe- notypes in other organisms},
author = {Tong, A H Y and Lesage, G and Bader, G D and Ding, H and Xu, H and Xin, X and Young, J and Berriz, G F and Brost, R L and Chang, M and Chen, Y and Cheng, X and Chua, G and Friesen, H and Goldberg, D S and Haynes, J and Humphries, C and He, G and Hussein, S and Ke, L and Krogan, N and Li, Z and Levinson, J N and Lu, H and Menard, P and Munyana, C and Parsons, A B and Ryan, O and Tonikian, R and Roberts, T and Sdicu, A M and Shapiro, J and Sheikh, B and Suter, B and Wong, S L and Zhang, L V and Zhu, H and Burd, C G and Munro, S and Sander, C and Rine, J and Greenblatt, J and Peter, M and Bretscher, A and Bell, G and Roth, F P and Brown, G W and Andrews, B and Bussey, H and Boone, C},
doi = {10.1126/science.1091317},
isbn = {1095-9203 (Electronic)
0036-8075 (Linking)},
issn = {1095-9203},
journal = {Science},
number = {February},
pages = {808--813},
pmid = {14764870},
title = {{Global Mapping of the Yeast Genetic Interaction Network}},
volume = {303},
year = {2004}
}
@article{Cho2014,
abstract = {RNA-guided endonucleases (RGENs), derived from the prokaryotic adaptive immune system known as CRISPR/Cas, enable targeted genome engineering in cells and organisms. RGENs are ribonucleoproteins that consist of guide RNA and Cas9, a protein component originated from Streptococcus pyogenes. These enzymes cleave chromosomal DNA, whose sequence is complementary, to guide RNA in a targeted manner, producing site-specific DNA double-strand breaks (DSBs), the repair of which gives rise to targeted genome modifications. Despite broad interest in RGEN-mediated genome editing, these nucleases are limited by off-target mutations and unwanted chromosomal translocations associated with off-target DNA cleavages. Here, we show that off-target effects of RGENs can be reduced below the detection limits of deep sequencing by choosing unique target sequences in the genome and modifying both guide RNA and Cas9. We found that both the composition and structure of guide RNA can affect RGEN activities in cells to reduce off-target effects. RGENs efficiently discriminated on-target sites from off-target sites that differ by two bases. Furthermore, exome sequencing analysis showed that no off-target mutations were induced by two RGENs in four clonal populations of mutant cells. In addition, paired Cas9 nickases, composed of D10A Cas9 and guide RNA, which generate two single-strand breaks (SSBs) or nicks on different DNA strands, were highly specific in human cells, avoiding off-target mutations without sacrificing genome-editing efficiency. Interestingly, paired nickases induced chromosomal deletions in a targeted manner without causing unwanted translocations. Our results highlight the importance of choosing unique target sequences and optimizing guide RNA and Cas9 to avoid or reduce RGEN-induced off-target mutations.},
author = {Cho, Seung Woo and Kim, Sojung and Kim, Yongsub and Kweon, Jiyeon and Kim, Heon Seok and Bae, Sangsu and Kim, Jin Soo},
doi = {10.1101/gr.162339.113},
isbn = {1549-5469},
issn = {10889051},
journal = {Genome Research},
number = {1},
pages = {132--141},
pmid = {24253446},
title = {{Analysis of off-target effects of CRISPR/Cas-derived RNA-guided endonucleases and nickases}},
volume = {24},
year = {2014}
}
@article{Tong2005,
abstract = {Summary Synthetic lethality occurs when the combination of two mutations leads to an inviable organism. Screens for synthetic lethal genetic interactions have been used extensively to identify genes whose products buffer one another or impinge on the same ... },
author = {Tong, A H Y and Boone, C},
journal = {METHODS IN MOLECULAR BIOLOGY-CLIFTON {\ldots}},
keywords = {E-MAP,Method,SGA},
title = {{Synthetic Genetic Array Analysis in Saccharomyces cerevisiae}},
url = {http://www.springerlink.com/index/ur4u10x723q88342.pdf},
year = {2005}
}
@article{Kramer2014,
abstract = {Putting new findings into the context of available literature knowledge is one approach to deal with the surge of high-throughput data results. Furthermore, prior knowledge can increase the performance and stability of bioinformatic algorithms, for example, methods for network reconstruction. In this review, we examine software packages for the statistical computing framework R, which enable the integration of pathway data for further bioinformatic analyses. Different approaches to integrate and visualize pathway data are identified and packages are stratified concerning their features according to a number of different aspects: data import strategies, the extent of available data, dependencies on external tools, integration with further analysis steps and visualization options are considered. A total of 12 packages integrating pathway data are reviewed in this manuscript. These are supplemented by five R-specific packages for visualization and six connector packages, which provide access to external tools.},
author = {Kramer, Frank and Bayerlov{\'{a}}, Michaela and Bei{\ss}barth, Tim},
doi = {10.3390/biology3010085},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Kramer, Bayerlov{\'{a}}, Bei{\ss}barth - 2014 - R-Based Software for the Integration of Pathway Data into Bioinformatic Algorithms.pdf:pdf},
isbn = {2079-7737 (Electronic)$\backslash$r2079-7737 (Linking)},
issn = {2079-7737},
journal = {Biology},
keywords = {BioPAX,Cytoscape,Pathway data,R-project,bioconductor,cytoscape,data,data integration,pathway data,rBiopaxParser,rbiopaxparser},
number = {1},
pages = {85--100},
pmid = {24833336},
title = {{R-Based Software for the Integration of Pathway Data into Bioinformatic Algorithms}},
url = {http://www.mdpi.com/2079-7737/3/1/85/},
volume = {3},
year = {2014}
}
@misc{Kang2012,
abstract = {Protein kinase C (PKC), a phospholipid-dependent serine/threonine kinase, appears to be involved in the signal transduction response to many hormones and growth factors; there are 11 different PKC isozymes. Because PKC isozymes directly and/or indirectly participate in signal transduction pathways of normal and transformed cells through phosphorylation of target proteins, it is critical to understand the diversity of the intracellular signaling pathways regulated by each PKC isozyme. Thus, PKC isozyme-specific substrates are useful to understand the characterization of the intracellular signaling pathways for each PKC isozyme. Consensus sequences and sequence information obtained from PKC target proteins are very important to design PKC isozyme-specific peptide substrates. Moreover, computational prediction programs of phosphorylation sites using a library of peptide substrates aid in the fast design of PKC isozyme-specific peptide substrates. Although a large number of target proteins and synthetic peptides for PKCs are known, only two peptide substrates (peptide 422-426 of murine elongation factor-1$\alpha$ and Alphatomega peptide) have been reported as PKC isozyme-specific peptide substrates. This discussion will review the literature concerning these native and synthetic PKC isozyme-specific peptide substrates and their design. {\textcopyright} 2012 Elsevier Inc.},
author = {Kang, Jeong Hun and Toita, Riki and Kim, Chan Woo and Katayama, Yoshiki},
booktitle = {Biotechnology Advances},
doi = {10.1016/j.biotechadv.2012.07.004},
issn = {07349750},
keywords = {Cellular signal,Enzyme,Isozymes,Peptide substrate,Phosphorylation,Protein kinase C},
pmid = {22841933},
title = {{Protein kinase C (PKC) isozyme-specific substrates and their design}},
year = {2012}
}
@misc{Stelling2004,
abstract = {Systems biology aims at an understanding of the genotype-phenotype relations brought about by cellular networks. Mathematical models as formal representations are central for handling the associated complexity. Recently, model-based analysis of microorganisms has begun, for instance, to reveal functional modules in metabolic and transcriptional networks, to predict cellular behavior from genome-scale physicochemical constraints, and to suggest novel design principles for well-studied bacterial subsystems such as chemotaxis. Guided by common themes such as modularity, optimality and robustness, iterative model development promises further progress towards a system-level understanding.},
author = {Stelling, J{\"{o}}rg},
booktitle = {Current Opinion in Microbiology},
doi = {10.1016/j.mib.2004.08.004},
isbn = {1369-5274 (Print) 1369-5274 (Linking)},
issn = {13695274},
pmid = {15451507},
title = {{Mathematical models in microbial systems biology}},
year = {2004}
}
@article{Andersson2008,
abstract = {Viruses shape microbial community structure and function by altering the fitness of their hosts and by promoting genetic exchange. The complexity of most natural ecosystems has precluded detailed studies of virus-host interactions. We reconstructed virus and host bacterial and archaeal genome sequences from community genomic data from two natural acidophilic biofilms. Viruses were matched to their hosts by analyzing spacer sequences that occur among clustered regularly interspaced short palindromic repeats (CRISPRs) that are a hallmark of virus resistance. Virus population genomic analyses provided evidence that extensive recombination shuffles sequence motifs sufficiently to evade CRISPR spacers. Only the most recently acquired spacers match coexisting viruses, which suggests that community stability is achieved by rapid but compensatory shifts in host resistance levels and virus population structure.},
author = {Andersson, Anders F and Banfield, Jillian F},
doi = {10.1126/science.1157358},
isbn = {1095-9203 (Electronic)$\backslash$n0036-8075 (Linking)},
issn = {1095-9203},
journal = {Science (New York, N.Y.)},
keywords = {Amino Acid Sequence,Archaea,Archaea: genetics,Archaea: physiology,Archaea: virology,Archaeal Viruses,Archaeal Viruses: genetics,Archaeal Viruses: physiology,Bacteria,Bacteria: genetics,Bacteria: virology,Bacterial Physiological Phenomena,Bacteriophages,Bacteriophages: genetics,Bacteriophages: physiology,Base Sequence,Biofilms,DNA, Intergenic,Ecosystem,Genome, Archaeal,Genome, Bacterial,Genome, Viral,Hydrogen-Ion Concentration,Molecular Sequence Data,Oligodeoxyribonucleotides,Recombination, Genetic,Repetitive Sequences, Nucleic Acid,Thermoplasmales,Thermoplasmales: genetics,Thermoplasmales: physiology,Thermoplasmales: virology,Viral Proteins,Viral Proteins: chemistry,Viral Proteins: genetics,Viral Proteins: physiology},
number = {5879},
pages = {1047--50},
pmid = {18497291},
title = {{Virus population dynamics and acquired virus resistance in natural microbial communities.}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/18497291},
volume = {320},
year = {2008}
}
@article{Mayes1999,
abstract = {Seven Sm proteins associate with U1, U2, U4 and U5 spliceosomal snRNAs and influence snRNP biogenesis. Here we describe a novel set of Sm-like (Lsm) proteins in Saccharomyces cerevisiae that interact with each other and with U6 snRNA. Seven Lsm proteins co-immunoprecipitate with the previously characterized Lsm4p (Uss1p) and interact with each other in two-hybrid analyses. Free U6 and U4/U6 duplexed RNAs co-immunoprecipitate with seven of the Lsm proteins that are essential for the stable accumulation of U6 snRNA. Analyses of U4/U6 di-snRNPs and U4/U6.U5 tri-snRNPs in Lsm-depleted strains suggest that Lsm proteins may play a role in facilitating conformational rearrangements of the U6 snRNP in the association-dissociation cycle of spliceosome complexes. Thus, Lsm proteins form a complex that differs from the canonical Sm complex in its RNA association(s) and function. We discuss the possible existence and functions of alternative Lsm complexes, including the likelihood that they are involved in processes other than pre-mRNA splicing.},
author = {Mayes, Andrew E. and Verdone, Loredana and Legrain, Pierre and Beggs, Jean D.},
doi = {10.1093/emboj/18.15.4321},
isbn = {0261-4189},
issn = {02614189},
journal = {EMBO Journal},
keywords = {Lsm,Sm proteins,Splicing,U6 snRNP,snRNP},
number = {15},
pages = {4321--4331},
pmid = {10428970},
title = {{Characterization of Sm-like proteins in yeast and their association with U6 snRNA}},
volume = {18},
year = {1999}
}
@article{Traynard2017,
abstract = {Here we present logic modeling as an approach to understand deregulation of signal transduction in disease and to characterize a drug's mode of action. We discuss how to build a logic model from the literature and experimental data and how to analyze the resulting model to obtain insights of relevance for systems pharmacology. Our workflow uses the free tools OmniPath (network reconstruction from the literature), CellNOpt (model fit to experimental data), MaBoSS (model analysis), and Cytoscape (visualization).},
author = {Traynard, Pauline and Tobalina, Luis and Eduati, Federica and Calzone, Laurence and Saez-Rodriguez, Julio},
doi = {10.1002/psp4.12225},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Traynard et al. - 2017 - Logic modeling in quantitative systems pharmacology.pdf:pdf},
issn = {21638306},
journal = {CPT: Pharmacometrics and Systems Pharmacology},
pmid = {28681552},
title = {{Logic modeling in quantitative systems pharmacology}},
year = {2017}
}
@misc{Willett2006,
abstract = {This paper summarizes recent work at the University of Sheffield on virtual screening methods that use 2D fingerprint measures of structural similarity. A detailed comparison of a large number of similarity coefficients demonstrates that the well-known Tanimoto coefficient remains the method of choice for the computation of fingerprint-based similarity, despite possessing some inherent biases related to the sizes of the molecules that are being sought. Group fusion involves combining the results of similarity searches based on multiple reference structures and a single similarity measure. We demonstrate the effectiveness of this approach to screening, and also describe an approximate form of group fusion, turbo similarity searching, that can be used when just a single reference structure is available. ?? 2006 Elsevier Ltd. All rights reserved.},
author = {Willett, Peter},
booktitle = {Drug Discovery Today},
doi = {10.1016/j.drudis.2006.10.005},
isbn = {1359-6446},
issn = {13596446},
number = {23-24},
pages = {1046--1053},
pmid = {17129822},
title = {{Similarity-based virtual screening using 2D fingerprints}},
volume = {11},
year = {2006}
}
@article{Herber1994,
abstract = {To be able to elucidate the function of cyclin D1 in the control of cell cycle progression and its role as an oncogene in tumorigenesis, it is of paramount importance to understand the mechanisms involved in the regulation of its expression. In the present study, we have cloned the human cyclin D1 gene and analysed the structure and function of 3kb of its 5'-flanking region. Several regulatory regions involved in both basal level and serum-induced expression were identified, two of which turned out to be of particular interest. One of these regions is involved in serum induction and is located 848-944 bp upstream of the initiation site. In agreement with this result, in vivo footprinting revealed a novel, strongly inducible protein binding site around positions -928 to -921. A second constitutively occupied binding site was mapped to a potential CRE at position -52. Cotransfection experiments showed that the cyclin D1 promoter is inducible by c-Jun, and that this induction is mediated predominantly through the protected putative CRE at -52.},
author = {Herber, B and Truss, M and Beato, M and M{\"{u}}ller, R},
isbn = {0950-9232 (Print)},
issn = {0950-9232},
journal = {Oncogene},
pmid = {8134134},
title = {{Inducible regulatory elements in the human cyclin D1 promoter.}},
year = {1994}
}
@article{Trott2010,
abstract = {AutoDock Vina, a new program for molecular docking and virtual screening, is presented. AutoDock Vina achieves an approximately two orders of magnitude speed-up compared with the molecular docking software previously developed in our lab (AutoDock 4), while also significantly improving the accuracy of the binding mode predictions, judging by our tests on the training set used in AutoDock 4 development. Further speed-up is achieved from parallelism, by using multithreading on multicore machines. AutoDock Vina automatically calculates the grid maps and clusters the results in a way transparent to the user.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Trott, Oleg and Olson, Arthur J.},
doi = {10.1002/jcc},
eprint = {NIHMS150003},
isbn = {1096-987X},
issn = {1096-987X},
journal = {Journal of Computational Chemistry},
number = {2},
pages = {455--61},
pmid = {20928852},
title = {{AutoDock Vina: Improving the Speed and Accuracy of Docking with a New Scoring Function, EfficientOptimization, and Multithreading}},
volume = {31},
year = {2010}
}
@article{Tong2006,
abstract = {Synthetic lethality occurs when the combination of two mutations leads to an inviable organism. Screens for synthetic lethal genetic interactions have been used extensively to identify genes whose products buffer one another or impinge on the same essential pathway. For the yeast Saccharomyces cerevisiae, we developed a method termed Synthetic Genetic Array (SGA) analysis, which offers an efficient approach for the systematic construction of double mutants and enables a global analysis of synthetic lethal genetic interactions. In a typical SGA screen, a query mutation is crossed to an ordered array of approx 5000 viable gene deletion mutants (representing approximately 80{\%} of all yeast genes) such that meiotic progeny harboring both mutations can be scored for fitness defects. This array-based approach automates yeast genetic analysis in general and can be easily adapted for a number of different screens, including genetic suppression, plasmid shuffling, dosage lethality, or suppression.},
author = {Tong, Amy Hin Yan and Boone, Charles},
doi = {10.1016/S0076-6879(10)70007-0},
isbn = {1064-3745 (Print)$\backslash$n1064-3745 (Linking)},
issn = {1064-3745},
journal = {Methods in molecular biology (Clifton, N.J.)},
keywords = {Alleles,Base Sequence,DNA Primers,DNA Primers: genetics,Fungal,Fungal: genetics,Gene Deletion,Genes,Genetic Techniques,Lethal,Mutation,Mycology,Mycology: methods,Oligonucleotide Array Sequence Analysis,Oligonucleotide Array Sequence Analysis: instrumen,Oligonucleotide Array Sequence Analysis: methods,Plasmids,Plasmids: genetics,Polymerase Chain Reaction,Saccharomyces cerevisiae,Saccharomyces cerevisiae: genetics,Spores},
number = {1},
pages = {171--92},
pmid = {16118434},
title = {{Synthetic genetic array analysis in Saccharomyces cerevisiae.}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/20946810},
volume = {313},
year = {2006}
}
@article{Rollie2012,
abstract = {Synthetic Biology offers qualitatively new perspectives on the benefits of industrially harnessed biological processes. The ability to modify and reprogramme natural biology increases the scope of tailored bioprocesses and yields attractive prospects beyond conventional Biotechnology. The present review summarises the major achievements and categorises them according to a hierarchy of system levels. Similar structures are known in the engineering sciences and might prove useful for the future development of Synthetic Biology. The hierarchy encompasses several levels of detail. Biological (macro-)molecules present the most detailed level (parts), followed by compartmentalised or non-compartmentalised modules (devices). In the next level, parts and devices are combined into functional cells and further into cellular communities. The manifold interactions between biological entities of the same hierarchical level or between different levels are accounted for by networks, primarily metabolic pathways and regulatory circuits. Networks of different types are represented as a superordinate hierarchical level that achieves full system integration. On all these levels, extensive and sound scientific foundations exist regarding experimental but also theoretical methods. These have led to diverse manifestations of Synthetic Biology on the parts and devices levels. Investigations involving synthetic components on the systems scale represent the most difficult and remain limited in number. A main challenge lies with the quantitative prediction of interactions between different entities across different scales. Systems-theoretical approaches provide important tools to analyse complex biological behaviour and can support the design of artificial biological systems. A promising strategy is seen in an efficient modularisation that reduces biological systems to a limited set of functional modules with well-characterised interfaces. For the design of synthetic biological systems the interactions across these interfaces should be standardised to reduce complexity. Yet, the identification of modules and standardised interaction routes remains a non-trivial problem. Furthermore, an appropriate platform that efficiently describes replication and evolutionary processes has to be developed in order to extend the achievements of Synthetic Biology into designed biological processes. {\textcopyright} 2011 Elsevier Ltd.},
author = {Rolli{\'{e}}, Sascha and Mangold, Michael and Sundmacher, Kai},
doi = {10.1016/j.ces.2011.10.068},
file = {:Users/ozlem/Dropbox/papers/Biological Networks/1-s2.0-S0009250911007925-main.pdf:pdf},
isbn = {0009-2509},
issn = {00092509},
journal = {Chemical Engineering Science},
keywords = {Biomolecular Engineering,Biosystems Engineering,Cell Biology,Process synthesis,Synthetic Biology,Systems Biology},
number = {1},
pages = {1--29},
pmid = {20233039},
title = {{Designing biological systems: Systems Engineering meets Synthetic Biology}},
volume = {69},
year = {2012}
}
@article{Bauer2010,
abstract = {Cancer invasion and metastasis depend on tumor-induced angiogenesis, the means by which cancer cells attract and maintain a blood supply. During angiogenesis, cellular processes are tightly coordinated by signaling molecules and their receptors. Understanding how endothelial cells synthesize multiple biochemical signals can catalyze the development of novel therapeutic strategies to combat cancer. This study is the first to propose a signal transduction model highlighting the cross-talk between key receptors involved in angiogenesis, namely the VEGF, integrin, and cadherin receptors. From experimental data, we construct a network model of receptor cross-talk and analyze its dynamics. We identify relationships between receptor activation combinations and cellular function, and show that cross-talk is crucial to phenotype determination. The network converges to a unique set of output states that correspond to known cell phenotypes: migratory, proliferating, quiescent, apoptotic, and it predicts one phenotype that challenges the "go or grow" hypothesis. Finally, we use the model to study protein inhibition and to suggest molecular targets for anti-angiogenic therapies. {\textcopyright} 2010 Elsevier Ltd.},
author = {Bauer, Amy L. and Jackson, Trachette L. and Jiang, Yi and Rohlf, Thimo},
doi = {10.1016/j.jtbi.2010.03.025},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Bauer et al. - 2010 - Receptor cross-talk in angiogenesis Mapping environmental cues to cell phenotype using a stochastic, Boolean signa.pdf:pdf},
isbn = {1095-8541 (Electronic)$\backslash$r0022-5193 (Linking)},
issn = {00225193},
journal = {Journal of Theoretical Biology},
keywords = {Cadherin,Cancer,Integrin,Signal transduction,VEGF-RTK},
pmid = {20307549},
title = {{Receptor cross-talk in angiogenesis: Mapping environmental cues to cell phenotype using a stochastic, Boolean signaling network model}},
year = {2010}
}
@article{Pinder2015,
abstract = {CRISPR is a genome-editing platform that makes use of the bacterially-derived endonuclease Cas9 to introduce DNA double-strand breaks at precise locations in the genome using complementary guide RNAs. We developed a nuclear domain knock-in screen, whereby the insertion of a gene encoding the green fluorescent protein variant Clover is inserted by Cas9-mediated homology directed repair (HDR) within the first exon of genes that are required for the structural integrity of subnuclear domains such as the nuclear lamina and promyelocytic leukemia nuclear bodies (PML NBs). Using this approach, we compared strategies for enhancing CRISPR-mediated HDR, focusing on known genes and small molecules that impact non-homologous end joining (NHEJ) and homologous recombination (HR). Ultimately, we identified the small molecule RS-1 as a potent enhancer of CRISPR-based genome editing, enhancing HDR 3- to 6-fold depending on the locus and transfection method. We also characterized U2OS human osteosarcoma cells expressing Clover-tagged PML and demonstrate that this strategy generates cell lines with PML NBs that are structurally and functionally similar to bodies in the parental cell line. Thus, the nuclear domain knock-in screen that we describe provides a simple means of rapidly evaluating methods and small molecules that have the potential to enhance Cas9-mediated HDR.},
archivePrefix = {arXiv},
arxivId = {arXiv:1011.1669v3},
author = {Pinder, Jordan and Salsman, Jayme and Dellaire, Graham},
doi = {10.1093/nar/gkv993},
eprint = {arXiv:1011.1669v3},
isbn = {9788578110796},
issn = {13624962},
journal = {Nucleic Acids Research},
number = {19},
pages = {9379--9392},
pmid = {26429972},
title = {{Nuclear domain 'knock-in' screen for the evaluation and identification of small molecule enhancers of CRISPR-based genome editing}},
volume = {43},
year = {2015}
}
@article{Roguev2007,
abstract = {Epistasis analysis, which reports on the extent to which the function of one gene depends on the presence of a second, is a powerful tool for studying the functional organization of the cell. Systematic genome-wide studies of epistasis, however, have been limited, with the majority of data being collected in the budding yeast, Saccharomyces cerevisiae. Here we present two 'pombe epistasis mapper' strategies, PEM-1 and PEM-2, which allow for high-throughput double mutant generation in the fission yeast, S. pombe. These approaches take advantage of a previously undescribed, recessive, cycloheximide-resistance mutation. Both systems can be used for genome-wide screens or for the generation of high-density, quantitative epistatic miniarray profiles (E-MAPs). Since S. cerevisiae and S. pombe are evolutionary distant, this methodology will provide insight into conserved biological pathways that are present in S. pombe, but not S. cerevisiae, and will enable a comprehensive analysis of the conservation of genetic interaction networks.},
author = {Roguev, Assen and Wiren, Marianna and Weissman, Jonathan S. and Krogan, Nevan J.},
doi = {10.1038/nmeth1098},
isbn = {1548-7091 (Print)$\backslash$r1548-7091 (Linking)},
issn = {15487091},
journal = {Nature Methods},
number = {10},
pages = {861--866},
pmid = {17893680},
title = {{High-throughput genetic interaction mapping in the fission yeast Schizosaccharomyces pombe}},
volume = {4},
year = {2007}
}
@article{Palomino-Schatzlein2013,
abstract = {An optimised extraction protocol for the analysis of Saccharomyces cerevisiae aqueous and organic metabolites by nuclear magnetic resonance spectroscopy that allows the identification and quantification of up to 50 different compounds is presented. The method was compared with other metabolic profiling protocols for S. cerevisiae, where generally different analytical techniques are applied for metabolite quantification. In addition, the analysis of intact S. cerevisiae cells by HRMAS was implemented for the first time as a complementary method. The optimised protocols were applied to study the metabolic effect of glucose and galactose on S. cerevisiae growth. Furthermore, the metabolic reaction of S. cerevisiae to osmotic stress has been studied.},
author = {Palomino-Sch{\"{a}}tzlein, Martina and Molina-Navarro, Maria Micaela and Tormos-P{\'{e}}rez, Marta and Rodr{\'{i}}guez-Navarro, Susana and Pineda-Lucena, Antonio},
doi = {10.1007/s00216-013-7271-9},
isbn = {0021601372},
issn = {16182642},
journal = {Analytical and Bioanalytical Chemistry},
keywords = {HRMAS,Metabolomics,NMR,Stress,Yeast},
number = {26},
pages = {8431--8441},
pmid = {23942588},
title = {{Optimised protocols for the metabolic profiling of S. cerevisiae by 1H-NMR and HRMAS spectroscopy}},
volume = {405},
year = {2013}
}
@article{Xing1996,
abstract = {A signaling pathway has been elucidated whereby growth factors activate the transcription factor cyclic adenosine monophosphate response element-binding protein (CREB), a critical regulator of immediate early gene transcription. Growth factor-stimulated CREB phosphorylation at serine-133 is mediated by the RAS-mitogen-activated protein kinase (MAPK) pathway. MAPK activates CREB kinase, which in turn phosphorylates and activates CREB. Purification, sequencing, and biochemical characterization of CREB kinase revealed that it is identical to a member of the pp90(RSK) family, RSK2. RSK2 was shown to mediate growth factor induction of CREB serine-133 phosphorylation both in vitro and in vivo. These findings identify a cellular function for RSK2 and define a mechanism whereby growth factor signals mediated by RAS and MAPK are transmitted to the nucleus to activate gene expression.},
author = {Xing, Jun and Ginty, David D. and Greenberg, Michael E.},
doi = {10.1126/science.273.5277.959},
isbn = {0036-8075 (Print)$\backslash$r0036-8075 (Linking)},
issn = {00368075},
journal = {Science},
pmid = {8688081},
title = {{Coupling of the RAS-MAPK pathway to gene activation by RSK2, a growth factor-regulated CREB kinase}},
year = {1996}
}
@article{Weng2018,
abstract = {The epidermal growth factor receptor (EGFR) plays important roles in cell survival, growth, differentiation, and tumorigenesis. Dysregulation of the EGFR is a common mechanism in cancer progression especially in non-small cell lung cancer (NSCLC).},
author = {Weng, Meng-Shih and Chang, Jer-Hwa and Hung, Wen-Yueh and Yang, Yi-Chieh and Chien, Ming-Hsien},
doi = {10.1186/s13046-018-0728-0},
issn = {1756-9966},
journal = {Journal of Experimental {\&} Clinical Cancer Research},
month = {mar},
number = {1},
pages = {61},
title = {{The interplay of reactive oxygen species and the epidermal growth factor receptor in tumor progression and drug resistance}},
url = {https://doi.org/10.1186/s13046-018-0728-0},
volume = {37},
year = {2018}
}
@misc{McLennan2006,
abstract = {Nudix hydrolases are found in all classes of organism and hydrolyse a wide range of organic pyrophosphates, including nucleoside di- and triphosphates, dinucleoside and diphosphoinositol polyphosphates, nucleotide sugars and RNA caps, with varying degrees of substrate specificity. Some superfamily members, such as Escherichia coli MicrotT, have the ability to degrade potentially mutagenic, oxidised nucleotides while others control the levels of metabolic intermediates and signalling compounds. In prokaryotes and simple eukaryo tes, the number of Nudix genes varies from 0 to over 30, reflecting the metabolic complexity and adaptability of the organism. Mammals have around 24 Nudix genes, several of which encode more than one variant. This review integrates the sizeable recent literature on these proteins with information from global functional genomic studies to provide some insights into the possible roles of different superfamily members in cellular metabolism and homeostasis and to stimulate discussion and further research into this ubiquitous protein family.},
author = {McLennan, A. G.},
booktitle = {Cellular and Molecular Life Sciences},
doi = {10.1007/s00018-005-5386-7},
isbn = {1420-682X (Print)},
issn = {1420682X},
keywords = {Antimutator,Decapping,Housecleaning,MutT,NUDT,Nucleotide metabolism,Nudix},
number = {2},
pages = {123--143},
pmid = {16378245},
title = {{The Nudix hydrolase superfamily}},
volume = {63},
year = {2006}
}
@article{Torquet2017,
abstract = {Individuality is a ubiquitous and well-conserved feature among animal species. The behavioral patterns of individual animals affect their respective role in the ecosystem and their prospects for survival. Even though some of the factors shaping individuality have been identified, the mechanisms underlying individuation are poorly understood and are generally considered to be genetics-based. Here we devised a large environment where mice live continuously, and observed that individuality, measured by both social and individual traits, emerged and settled within the group. Midbrain dopamine neurons underwent neurophysiological adaptations that mirrored this phenotypic divergence in individual behaviors. Strikingly, modifying the social environment resulted in a fast re-adaptation of both the animal's personality and its dopaminergic signature. These results indicate that individuality can rapidly evolve upon social challenges, and does not just depend on the genetic or epigenetic initial status of the animal.},
author = {Torquet, Nicolas and Marti, Fabio and Campart, Cynthia and Tolu, Stefania and Nguyen, Claire and Oberto, Virginie and Naud{\'{e}}, J{\'{e}}r{\'{e}}mie and Didienne, Steve and Jezequel, Soizic and Gouestre, Laura Le and Debray, Nicolas and Mourot, Alexandre and Mariani, Jean and Faure, Philippe},
doi = {10.1101/236554},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Torquet et al. - 2017 - Social interactions impact on the dopaminergic system and drive individuality.pdf:pdf},
isbn = {4146701805},
issn = {2041-1723},
journal = {bioRxiv},
number = {2018},
pages = {236554},
pmid = {30082725},
publisher = {Springer US},
title = {{Social interactions impact on the dopaminergic system and drive individuality}},
url = {https://www.biorxiv.org/content/early/2017/12/19/236554},
year = {2017}
}
@article{Torbeev2011,
abstract = {We have used chemical protein synthesis and advanced physical methods to probe dynamics-function correlations for the HIV-1 protease, an enzyme that has received considerable attention as a target for the treatment of AIDS. Chemical synthesis was used to prepare a series of unique analogues of the HIV-1 protease in which the flexibility of the "flap" structures (residues 37-61 in each monomer of the homodimeric protein molecule) was systematically varied. These analogue enzymes were further studied by X-ray crystallography, NMR relaxation, and pulse-EPR methods, in conjunction with molecular dynamics simulations. We show that conformational isomerization in the flaps is correlated with structural reorganization of residues in the active site, and that it is preorganization of the active site that is a rate-limiting factor in catalysis.},
author = {Torbeev, V. Y. and Raghuraman, H. and Hamelberg, D. and Tonelli, M. and Westler, W. M. and Perozo, E. and Kent, S. B. H.},
doi = {10.1073/pnas.1111202108},
isbn = {1091-6490 (Electronic)$\backslash$r0027-8424 (Linking)},
issn = {0027-8424},
journal = {Proceedings of the National Academy of Sciences},
number = {52},
pages = {20982--20987},
pmid = {22158985},
title = {{Protein conformational dynamics in the mechanism of HIV-1 protease catalysis}},
url = {http://www.pnas.org/cgi/doi/10.1073/pnas.1111202108},
volume = {108},
year = {2011}
}
@article{Odajima2000,
abstract = {Tyrosine kinase oncoproteins cause simultaneous activation of multiple intracellular signaling pathways. However, the precise mechanisms by which individual pathways induce oncogenesis are not well understood. We have investigated the roles of individual signaling pathways in v-Src-dependent cell growth and survival by inhibiting one particular pathway. v-Src induced constitutive activation of signal transducers and activators of transcription 3 (STAT3), phosphatidylinositol 3-kinase, and Ras in murine Ba/F3 cells and led to factor-independent proliferation. Dominant-negative mutants of STAT3 (STAT3D) and phosphatidylinositol 3-kinase (Deltap85) inhibited v-Src-dependent growth by approximately 60 and approximately 40{\%}, respectively. Moreover, dominant-negative Ras (N17) induced severe apoptosis, which was accompanied by down-regulation of Bcl-2 and activation of caspase-3. Although cells overexpressing Bcl-2 or caspase-3 inhibitors remained viable even when N17 was expressed, the growth was reduced by approximately 85{\%}. During N17- and STAT3D-induced growth suppression, expression of cyclin D2, cyclin D3, c-myc, and c-fos was suppressed by N17, whereas that of cyclin D2, cyclin E, and c-myc was suppressed by STAT3D. Thus, v-Src-activated Ras and STAT3 are involved in distinct but partly overlapping transcriptional regulation of cell cycle regulatory molecules. These results suggest that the full oncogenic activity of v-Src requires simultaneous activation of multiple signalings, in which Ras is particularly required for survival.},
author = {Odajima, Junko and Matsumura, Itaru and Sonoyama, Junko and Daino, Hanako and Kawasaki, Akira and Tanaka, Hirokazu and Inohara, Naohiro and Kitamura, Toshio and Downward, Julian and Nakajima, Koichi and Hirano, Toshio and Kanakura, Yuzuru},
doi = {10.1074/jbc.M001606200},
isbn = {8166879387},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {10918073},
title = {{Full oncogenic activities of v-Src are mediated by multiple signaling pathways: Ras as an essential mediator for cell survival}},
year = {2000}
}
@article{Graus-Porta1997,
abstract = {We have analyzed ErbB receptor interplay induced by the epidermal growth factor (EGF)-related peptides in cell lines naturally expressing the four ErbB receptors. Down-regulation of cell surface ErbB-1 or ErbB-2 by intracellular expression of specific antibodies has allowed us to delineate the role of these receptors during signaling elicited by: EGF and heparin binding EGF (HB-EGF), ligands of ErbB-1; betacellulin (BTC), a ligand of ErbB-1 and ErbB-4; and neu differentiation factor (NDF), a ligand of ErbB-3 and ErbB-4. Ligand-induced ErbB receptor heterodimerization follows a strict hierarchy and ErbB-2 is the preferred heterodimerization partner of all ErbB proteins. NDF-activated ErbB-3 or ErbB-4 heterodimerize with ErbB-1 only when no ErbB-2 is available. If all ErbB receptors are present, NDF receptors preferentially dimerize with ErbB-2. Furthermore, EGF- and BTC-induced activation of ErbB-3 is impaired in the absence of ErbB-2, suggesting that ErbB-2 has a role in the lateral transmission of signals between other ErbB receptors. Finally, ErbB-1 activated by all EGF-related peptides (EGF, HB-EGF, BTC and NDF) couples to SHC, whereas only ErbB-1 activated by its own ligands associates with and phosphorylates Cbl. These results provide the first biochemical evidence that a given ErbB receptor has distinct signaling properties depending on its dimerization.},
author = {Graus-Porta, Diana and Beerli, Roger R. and Daly, John M. and Hynes, Nancy E.},
doi = {10.1093/emboj/16.7.1647},
isbn = {0261-4189 (Print)},
issn = {02614189},
journal = {EMBO Journal},
keywords = {ErbB receptors,Lateral signaling,Receptor dimerization,Signal transduction,Single chain antibody},
pmid = {9130710},
title = {{ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling}},
year = {1997}
}
@article{Rep2000,
abstract = {We have analyzed the transcriptional response to osmotic shock in the yeast Saccharomyces cerevisiae. The mRNA level of 186 genes increased at least 3-fold after a shift to NaCl or sorbitol, whereas that of more than 100 genes was at least 1.5-fold diminished. Many induced genes encode proteins that presumably contribute to protection against different types of damage or encode enzymes in glycerol, trehalose, and glycogen metabolism. Several genes, which encode poorly expressed isoforms of enzymes in carbohydrate metabolism, were induced. The high osmolarity glycerol (HOG) pathway is required for full induction of many but not all genes. The recently characterized Hot1p transcription factor is required for normal expression of a subset of the HOG pathway-dependent responses. Stimulated expression of the genes that required the general stress-response transcription factors Msn2p and Msn4p was also reduced in a hog1 mutant, suggesting that Msn2p/Msn4p might be regulated by the HOG pathway. The expression of genes that are known to be controlled by the mating pheromone response pathway was stimulated by osmotic shock specifically in a hog1 mutant. Inappropriate activation of the mating response may contribute to the growth defect of a hog1 mutant in high osmolarity medium.},
author = {Rep, Martijn and Krantz, Marcus and Thevelein, Johan M. and Hohmann, Stefan},
doi = {10.1074/jbc.275.12.8290},
isbn = {0021-9258 (Print)$\backslash$r0021-9258 (Linking)},
issn = {00219258},
journal = {Journal of Biological Chemistry},
number = {12},
pages = {8290--8300},
pmid = {10722658},
title = {{The transcriptional response of Saccharomyces cerevisiae to osmotic shock. Hot1p and Msn2p/Msn4p are required for the induction of subsets of high osmolarity glycerol pathway-dependent genes}},
volume = {275},
year = {2000}
}
@article{Ji1997,
abstract = {The activation of many tyrosine kinases leads to the phosphorylation and activation of phospholipase C-$\gamma$1 (PLC-$\gamma$1). To examine the biological function of this protein, homologous recombination has been used to selectively disrupt the Plcg1 gene in mice. Homozygous disruption of Plcg1 results in embryonic lethality at approximately embryonic day (E) 9.0. Histological analysis indicates that Plcg1 (−/−) embryos appear normal at E 8.5 but fail to continue normal development and growth beyond E 8.5–E9.0. These results clearly demonstrate that PLC-$\gamma$1 with, by inference, its capacity to mobilize second messenger molecules is an essential signal transducing molecule whose absence is not compensated by other signaling pathways or other genes encoding PLC isozymes.PLC,phospholipase C;ES,embryonic stem;TV,targeting vector;MEF,mouse embryonic fibroblasts;E,embryonic day},
author = {Ji, Qun-sheng and Winnier, Glenn E and Niswender, Kevin D and Horstman, Debra and Wisdom, Ron and Magnuson, Mark A and Carpenter, Graham},
doi = {10.1073/pnas.94.7.2999},
journal = {Proceedings of the National Academy of Sciences},
month = {apr},
number = {7},
pages = {2999 LP  -- 3003},
title = {{Essential role of the tyrosine kinase substrate phospholipase C-$\gamma$1 in mammalian growth and development}},
url = {http://www.pnas.org/content/94/7/2999.abstract},
volume = {94},
year = {1997}
}
@article{Barrangou2007,
abstract = {Clustered regularly interspaced short palindromic repeats (CRISPR) are a distinctive feature of the genomes of most Bacteria and Archaea and are thought to be involved in resistance to bacteriophages. We found that, after viral challenge, bacteria integrated new spacers derived from phage genomic sequences. Removal or addition of particular spacers modified the phage-resistance phenotype of the cell. Thus, CRISPR, together with associated cas genes, provided resistance against phages, and resistance specificity is determined by spacer-phage sequence similarity.},
author = {Barrangou, R. and Fremaux, C. and Deveau, H. and Richards, M. and Boyaval, P. and Moineau, S. and Romero, D. A. and Horvath, P.},
doi = {10.1126/science.1138140},
isbn = {1095-9203 (Electronic)$\backslash$r0036-8075 (Linking)},
issn = {0036-8075},
journal = {Science},
number = {5819},
pages = {1709--1712},
pmid = {17379808},
title = {{CRISPR Provides Acquired Resistance Against Viruses in Prokaryotes}},
url = {http://www.sciencemag.org/cgi/doi/10.1126/science.1138140},
volume = {315},
year = {2007}
}
@article{Srivastava2012,
abstract = {DNA Ligase IV is responsible for sealing of double-strand breaks (DSBs) during nonhomologous end-joining (NHEJ). Inhibiting Ligase IV could result in amassing of DSBs, thereby serving as a strategy toward treatment of cancer. Here, we identify a molecule, SCR7 that inhibits joining of DSBs in cell-free repair system. SCR7 blocks Ligase IV-mediated joining by interfering with its DNA binding but not that of T4 DNA Ligase or Ligase I. SCR7 inhibits NHEJ in a Ligase IV-dependent manner within cells, and activates the intrinsic apoptotic pathway. More importantly, SCR7 impedes tumor progression in mouse models and when coadministered with DSB-inducing therapeutic modalities enhances their sensitivity significantly. This inhibitor to target NHEJ offers a strategy toward the treatment of cancer and improvement of existing regimens. ?? 2012 Elsevier Inc.},
author = {Srivastava, Mrinal and Nambiar, Mridula and Sharma, Sheetal and Karki, Subhas S. and Goldsmith, G. and Hegde, Mahesh and Kumar, Sujeet and Pandey, Monica and Singh, Ram K. and Ray, Pritha and Natarajan, Renuka and Kelkar, Madhura and De, Abhijit and Choudhary, Bibha and Raghavan, Sathees C.},
doi = {10.1016/j.cell.2012.11.054},
isbn = {0092-8674},
issn = {00928674},
journal = {Cell},
number = {7},
pages = {1474--1487},
pmid = {23260137},
title = {{An inhibitor of nonhomologous end-joining abrogates double-strand break repair and impedes cancer progression}},
volume = {151},
year = {2012}
}
@article{Baryshnikova2010a,
abstract = {A genetic interaction occurs when the combination of two mutations leads to an unexpected phenotype. Screens for synthetic genetic interactions have been used extensively to identify genes whose products are functionally related. In particular, synthetic lethal genetic interactions often identify genes that buffer one another or impinge on the same essential pathway. For the yeast Saccharomyces cerevisiae, we developed a method termed synthetic genetic array (SGA) analysis, which offers an efficient approach for the systematic construction of double mutants and enables a global analysis of synthetic genetic interactions. In a typical SGA screen, a query mutation is crossed to an ordered array of ∼5000 viable gene deletion mutants (representing ∼80{\%} of all yeast genes) such that meiotic progeny harboring both mutations can be scored for fitness defects. This approach can be extended to all ∼6000 genes through the use of yeast arrays containing mutants carrying conditional or hypomorphic alleles of essential genes. Estimating the fitness for the two single mutants and their corresponding double mutant enables a quantitative measurement of genetic interactions, distinguishing negative (synthetic lethal) and positive (within pathway and suppression) interactions. The profile of genetic interactions represents a rich phenotypic signature for each gene and clustering genetic interaction profiles group genes into functionally relevant pathways and complexes. This array-based approach automates yeast genetic analysis in general and can be easily adapted for a number of different genetic screens or combined with high-content screening systems to quantify the activity of specific reporters in genome-wide sets of single or more complex multiple mutant backgrounds. Comparison of genetic and chemical-genetic interaction profiles offers the potential to link bioactive compounds to their targets. Finally, we also developed an SGA system for the fission yeast Schizosaccharomyces pombe, providing another model system for comparative analysis of genetic networks and testing the conservation of genetic networks over millions of years of evolution. {\textcopyright} 2010 Elsevier Inc. All rights reserved.},
author = {Baryshnikova, Anastasia and Costanzo, Michael and Dixon, Scott and Vizeacoumar, Franco J. and Myers, Chad L. and Andrews, Brenda and Boone, Charles},
doi = {10.1016/S0076-6879(10)70007-0},
isbn = {9780123751720},
issn = {00766879},
journal = {Methods in Enzymology},
number = {C},
pages = {145--179},
pmid = {20946810},
title = {{Synthetic genetic array (SGA) analysis in Saccharomyces cerevisiae and schizosaccharomyces pombe}},
volume = {470},
year = {2010}
}
@incollection{Warringer2014,
abstract = {As our ability to acquire massive amounts of information about genome variation accelerates it is becoming increasingly clear that to make maximum use of this information we also need well-structured, systematic data on the phenotypic consequences of genomic changes. Phenomics is the new discipline of using standardized measurement techniques to characterize the phenotypic effects of random or systematic genome modifications (for example randomly generated mutations or systematic gene knockouts). This approach is now being used in an increasing range of species and systems. In this book, experts working in phenomics in most of the major species and systems that are currently being studied present overviews of the field from their different, but overlapping perspectives.},
author = {Warringer, Jonas and Blomberg, Anders},
booktitle = {Phenomics},
isbn = {978-1-4665-9096-0; 978-1-4665-9095-3},
pages = {172--207},
title = {{Yeast Phenomics-Large-scale Mapping of the Genetic Basis for Organismal Traits}},
year = {2014}
}
@article{Lund1990,
abstract = {To assess the functional significance of phosphorylation of the epidermal growth factor (EGF) receptor at Thr654, we compared the effects of 12-O-tetradecanoyl-13-acetate (TPA) on ligand-induced internalization and down-regulation between wild-type and mutant receptors that contain an alanine substitution at position 654. Activation of protein kinase C with TPA blocked EGF-induced internalization and down-regulation of Thr654 receptors and inhibited in vivo tyrosine kinase activity by 80{\%}. TPA did not inhibit transferrin receptor internalization or constitutive EGF receptor internalization, suggesting that protein kinase C activation inhibits only the ligand-induced process. Inhibition by TPA of induced internalization, down-regulation, and kinase activity required threonine at position 654 since full-length Ala654 EGF receptors were significantly resistant to TPA inhibition of these ligand-induced activities. However, C'-terminal truncation further enhanced this resistance to TPA inhibition. The EGF-dependent internalization of kinase-inactive receptors truncated at residue 1022 was also impaired by TPA in Thr654 receptors, but not in Ala654 receptors, indicating that phosphorylation at Thr654 also interferes with tyrosine kinase-independent receptor activities. We conclude that the dominant regulatory effect of protein kinase C on the EGF receptor is mediated through phosphorylation at Thr654 which effectively inactivates the receptor. The submembrane region of the EGF receptor appears to regulate transmission of conformational information from the extracellular ligand-binding site to the cytoplasmic kinase and regulatory domains.},
author = {Lund, K. A. and Lazar, C. S. and Chen, W. S. and Walsh, B. J. and Welsh, J. B. and Herbst, J. J. and Walton, G. M. and Rosenfeld, M. G. and Gill, G. N. and Wiley, H. S.},
isbn = {0021-9258 (Print)$\backslash$r0021-9258 (Linking)},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {2173710},
title = {{Phosphorylation of the epidermal growth factor receptor at threonine 654 inhibits ligand-induced internalization and down-regulation}},
year = {1990}
}
@article{Yu2015,
abstract = {The bacterial CRISPR-Cas9 system has emerged as an effective tool for sequence-specific gene knockout through non-homologous end joining (NHEJ), but it remains inefficient for precise editing of genome sequences. Here we develop a reporter-based screening approach for high-throughput identification of chemical compounds that can modulate precise genome editing through homology-directed repair (HDR). Using our screening method, we have identified small molecules that can enhance CRISPR-mediated HDR efficiency, 3-fold for large fragment insertions and 9-fold for point mutations. Interestingly, we have also observed that a small molecule that inhibits HDR can enhance frame shift insertion and deletion (indel) mutations mediated by NHEJ. The identified small molecules function robustly in diverse cell types with minimal toxicity. The use of small molecules provides a simple and effective strategy to enhance precise genome engineering applications and facilitates the study of DNA repair mechanisms in mammalian cells.},
archivePrefix = {arXiv},
arxivId = {15334406},
author = {Yu, Chen and Liu, Yanxia and Ma, Tianhua and Liu, Kai and Xu, Shaohua and Zhang, Yu and Liu, Honglei and {La Russa}, Marie and Xie, Min and Ding, Sheng and Qi, Lei S.},
doi = {10.1016/j.stem.2015.01.003},
eprint = {15334406},
isbn = {1875-9777 (Electronic)},
issn = {18759777},
journal = {Cell Stem Cell},
number = {2},
pages = {142--147},
pmid = {25658371},
title = {{Small molecules enhance crispr genome editing in pluripotent stem cells}},
volume = {16},
year = {2015}
}
@article{Pannone2001,
abstract = {The U6 small nuclear ribonucleoprotein is a critical component of the eukaryotic spliceosome. The first protein that binds the U6 snRNA is the La protein, an abundant phosphoprotein that binds the 3' end of many nascent small RNAs. A complex of seven Sm-like proteins, Lsm2-Lsm8, also binds the 3' end of U6 snRNA. A mutation within the Sm motif of Lsm8p causes Saccharomyces cerevisiae cells to require the La protein Lhp1p to stabilize nascent U6 snRNA. Here we describe functional interactions between Lhp1p, the Lsm proteins, and U6 snRNA. LSM2 and LSM4, but not other LSM genes, act as allele-specific, low-copy suppressors of mutations in Lsm8p. Overexpression of LSM2 in the lsm8 mutant strain increases the levels of both Lsm8p and U6 snRNPs. In the presence of extra U6 snRNA genes, LSM8 becomes dispensable for growth, suggesting that the only essential function of LSM8 is in U6 RNA biogenesis or function. Furthermore, deletions of LSM5, LSM6, or LSM7 cause LHP1 to become required for growth. Our experiments are consistent with a model in which Lsm2p and Lsm4p contact Lsm8p in the Lsm2-Lsm8 ring and suggest that Lhp1p acts redundantly with the entire Lsm2-Lsm8 complex to stabilize nascent U6 snRNA.$\backslash$n},
author = {Pannone, Barbara K. and Kim, Sang Do and Noe, Dennis A. and Wolin, Sandra L.},
isbn = {0016-6731},
issn = {00166731},
journal = {Genetics},
number = {1},
pages = {187--196},
pmid = {11333229},
title = {{Multiple functional interactions between components of the Lsm2-Lsm8 complex, U6 snRNA, and the yeast La protein}},
volume = {158},
year = {2001}
}
@article{Gomez-Cabrero2014,
abstract = {Chronic diseases (CD) are generating a dramatic societal burden worldwide that is expected to persist over the next decades. The challenges posed by the epidemics of CD have triggered a novel health paradigm with major consequences on the traditional concept of disease and with a profound impact on key aspects of healthcare systems. We hypothesized that the development of a systems approach to understand CD together with the generation of an ecosystem to transfer the acquired knowledge into the novel healthcare scenario may contribute to a cost-effective enhancement of health outcomes. To this end, we designed the Synergy-COPD project wherein the heterogeneity of chronic obstructive pulmonary disease (COPD) was addressed as a use case representative of CD. The current manuscript describes main features of the project design and the strategies put in place for its development, as well the expected outcomes during the project life-span. Moreover, the manuscript serves as introductory and unifying chapter of the different papers associated to the Supplement describing the characteristics, tools and the objectives of Synergy-COPD.},
author = {Gomez-Cabrero, D and Lluch-Ariet, M and Tegner, J and Cascante, M and Miralles, F and Roca, J and consortium Synergy, Copd},
doi = {10.1186/1479-5876-12-S2-S2},
file = {:Users/ozlem/Desktop/papers/Disease Map Papers/1479-5876-12-S2-S2.pdf:pdf},
isbn = {1479-5876 (Electronic)$\backslash$r1479-5876 (Linking)},
journal = {J Transl Med},
keywords = {*Decision Support Systems, Clinical,Chronic Disease/therapy,Comorbidity,Computer Simulation,Delivery of Health Care,Electronic Health Records,Humans,Models, Organizational,Muscle, Skeletal/physiopathology,Program Development,Pulmonary Disease, Chronic Obstructive/*physiopath,Telemedicine/methods},
number = {Suppl 2},
pages = {S2},
pmid = {25472826},
title = {{Synergy-COPD: a systems approach for understanding and managing chronic diseases}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/25472826},
volume = {12 Suppl 2},
year = {2014}
}
@misc{Marks2005,
abstract = {No abstract.},
author = {Marks, Jonathan},
booktitle = {Evolutionary Anthropology},
doi = {10.1002/evan.20049},
isbn = {10601538},
issn = {10601538},
number = {2},
pages = {49--53},
title = {{Phylogenetic trees and evolutionary forests}},
volume = {14},
year = {2005}
}
@article{Kirwan2012,
abstract = {Systems biology methods using large-scale "omics" data sets face unique challenges: integrating and analyzing near limitless data space, while recognizing and removing systematic variation or noise. Herein we propose a complementary multivariate analysis workflow to both integrate "omics" data from disparate sources and analyze the results for specific and unique sample correlations. This workflow combines principal component analysis (PCA), orthogonal projections to latent structures discriminate analysis (OPLS-DA), orthogonal 2 projections to latent structures (O2PLS), and shared and unique structures (SUS) plots. The workflow is demonstrated using data from a study in which ApoE3Leiden mice were fed an atherogenic diet consisting of increasing cholesterol levels followed by therapeutic intervention (fenofibrate, rosuvastatin, and LXR activator T-0901317). The levels of structural lipids (lipidomics) and free fatty acids in liver were quantified via liquid chromatography-mass spectrometry (LC-MS). The complementary workflow identified diglycerides as key hepatic metabolites affected by dietary cholesterol and drug intervention. Modeling of the three therapeutics for mice fed a high-cholesterol diet further highlighted diglycerides as metabolites of interest in atherogenesis, suggesting a role in eliciting chronic liver inflammation. In particular, O2PLS-based SUS2 plots showed that treatment with T-0901317 or rosuvastatin returned the diglyceride profile in high-cholesterol-fed mice to that of control animals.},
author = {Kirwan, Gemma M. and Johansson, Erik and Kleemann, Robert and Verheij, Elwin R. and Wheelock, {\AA}sa M. and Goto, Susumu and Trygg, Johan and Wheelock, Craig E.},
doi = {10.1021/ac301269r},
isbn = {1520-6882 (Electronic)$\backslash$r0003-2700 (Linking)},
issn = {00032700},
journal = {Analytical Chemistry},
pmid = {22856472},
title = {{Building multivariate systems biology models}},
year = {2012}
}
@misc{Larive2015,
abstract = {A pplications of NMR for metabolomics and metabolic profiling continue to grow rapidly as does the refinement of methods for the measurement, analysis, and interpretation of complex data sets. Metabolomics (metabonomics) is a set of global measurements performed on biological samples with the goal of quantifying as many metabolites as possible and evaluating changes in metabolite levels as a result of an applied stress. Metabolic profiling experiments follow a more limited set of metabolites often through specific pathways. NMR is also well suited for metabolite fingerprinting, which involves the comprehensive and simultaneous analysis of a wide variety of compounds. For the purpose of this Review, we do not distin-guish between metabolomics and metabonomics and have elected to use the term metabolomics throughout. Figure 1 illustrates the rapid growth in publications on topics that include the keywords NMR and metabolomics/metabonomics since the year 2000. Due to space limitations, this Review covers only papers published between 2011 and the first half of 2014.},
author = {Larive, Cynthia K. and Barding, Gregory A. and Dinges, Meredith M.},
booktitle = {Analytical Chemistry},
doi = {10.1021/ac504075g},
isbn = {0003-2700},
issn = {15206882},
number = {1},
pages = {133--146},
pmid = {25375201},
title = {{NMR spectroscopy for metabolomics and metabolic profiling}},
volume = {87},
year = {2015}
}
@techreport{Oktem2002,
abstract = {Random Boolean networks are among the most popular model systems used for modelling the gene regulatory networks due to their answering of the many biological questions in a realistic way, insights into the overall behavior of large genetic networks and suitability for inference. However , discrete time Boolean networks have serious limitations in simulating non-repeating complex dynamic systems and incorporating the biochemical information on the reaction rates. In this work we introduce continuous-time Boolean network structure to simulate the genomic regulation as a binary complex dynamic system, discuss their potential of solving the problems of the conventional discrete time Boolean networks and develop a framework for simulating continuous time Boolean networks.},
author = {Oktem, Hakan and Yli-Harja, Olli and Egiazarian, Karen and Astola, J T and {\"{O}}ktem, Hakan and Pearson, Ronald and Nicorici, Daniel and Astola, Jaakko},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Oktem et al. - 2002 - A Computational Model For Simulating Continuous Time Boolean Networks Efficient implementation of nonlinear filter.pdf:pdf},
title = {{A Computational Model For Simulating Continuous Time Boolean Networks Efficient implementation of nonlinear filters View project super-resolution View project A COMPUTATIONAL MODEL FOR SIMULATING CONTINUOUS TIME BOOLEAN NETWORKS}},
url = {https://www.researchgate.net/publication/2560888},
year = {2002}
}
@article{Lipinski2001,
abstract = {Experimental and computational approaches to estimate solubility and permeability in discovery and development settings are described. In the discovery setting `the rule of 5' predicts that poor absorption or permeation is more likely when there are more than 5 H-bond donors, 10 H-bond acceptors, the molecular weight (MWT) is greater than 500 and the calculated Log P (CLogP) is greater than 5 (or MlogP{\textgreater}4.15). Computational methodology for the rule-based Moriguchi Log P (MLogP) calculation is described. Turbidimetric solubility measurement is described and applied to known drugs. High throughput screening (HTS) leads tend to have higher MWT and Log P and lower turbidimetric solubility than leads in the pre-HTS era. In the development setting, solubility calculations focus on exact value prediction and are difficult because of polymorphism. Recent work on linear free energy relationships and Log P approaches are critically reviewed. Useful predictions are possible in closely related analog series when coupled with experimental thermodynamic solubility measurements.},
author = {Lipinski, C A and Lombardo, F and Dominy, B W and Feeney, P J},
doi = {http://dx.doi.org/10.1016/S0169-409X(00)00129-0},
isbn = {0169-409X},
issn = {0169-409X},
journal = {Advanced Drug Delivery Reviews},
keywords = {Computational alert,H-Bond donors and acceptors,MLogP,MWT,Poor absorption or permeation,Rule of 5,Solubility calculation,Thermodynamic solubility,Turbidimetric solubility},
number = {1–3},
pages = {3--26},
title = {{Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings1}},
url = {http://www.sciencedirect.com/science/article/pii/S0169409X00001290},
volume = {46},
year = {2001}
}
@article{Stoll2017,
abstract = {Motivation Modeling of signaling pathways is an important step towards the understanding and the treatment of diseases such as cancers, HIV or auto-immune diseases. MaBoSS is a software that allows to simulate populations of cells and to model stochastically the intracellular mechanisms that are deregulated in diseases. MaBoSS provides an output of a Boolean model in the form of time-dependent probabilities, for all biological entities (genes, proteins, phenotypes, etc.) of the model. Results We present a new version of MaBoSS (2.0), including an updated version of the core software and an environment. With this environment, the needs for modeling signaling pathways are facilitated, including model construction, visualization, simulations of mutations, drug treatments and sensitivity analyses. It offers a framework for automated production of theoretical predictions. Availability and Implementation MaBoSS software can be found at https://maboss.curie.fr , including tutorials on existing models and examples of models. Contact gautier.stoll@upmc.fr or laurence.calzone@curie.fr. Supplementary information Supplementary data are available at Bioinformatics online.},
author = {Stoll, Gautier and Caron, Barth{\'{e}}l{\'{e}}my and Viara, Eric and Dugourd, Aur{\'{e}}lien and Zinovyev, Andrei and Naldi, Aur{\'{e}}lien and Kroemer, Guido and Barillot, Emmanuel and Calzone, Laurence},
doi = {10.1093/bioinformatics/btx123},
file = {:Users/ozlem/Desktop/Tools/btx123.pdf:pdf},
issn = {14602059},
journal = {Bioinformatics},
number = {14},
pages = {2226--2228},
pmid = {28881959},
title = {{MaBoSS 2.0: An environment for stochastic Boolean modeling}},
volume = {33},
year = {2017}
}
@misc{Leggett2013,
abstract = {The processes of quality assessment and control are an active area of research at The Genome Analysis Centre (TGAC). Unlike other sequencing centers that often concentrate on a certain species or technology, TGAC applies expertise in genomics and bioinformatics to a wide range of projects, often requiring bespoke wet lab and in silico workflows. TGAC is fortunate to have access to a diverse range of sequencing and analysis platforms, and we are at the forefront of investigations into library quality and sequence data assessment. We have developed and implemented a number of algorithms, tools, pipelines and packages to ascertain, store, and expose quality metrics across a number of next-generation sequencing platforms, allowing rapid and in-depth cross-platform Quality Control (QC) bioinformatics. In this review, we describe these tools as a vehicle for data-driven informatics, offering the potential to provide richer context for downstream analysis and to inform experimental design.},
author = {Leggett, Richard M. and Ramirez-Gonzalez, Ricardo H. and Clavijo, Bernardo J. and Waite, Darren and Davey, Robert P.},
booktitle = {Frontiers in Genetics},
doi = {10.3389/fgene.2013.00288},
isbn = {1664-8021 (Print)$\backslash$r1664-8021 (Linking)},
issn = {16648021},
keywords = {Bioinformatics tools,Contamination screening,NGS data analysis,QC,Quality assessment and improvement,Quality control,Run statistics,Sequence analysis},
number = {DEC},
pmid = {24381581},
title = {{Sequencing quality assessment tools to enable data-driven informatics for high throughput genomics}},
volume = {4},
year = {2013}
}
@article{Doudna2014,
abstract = {The advent of facile genome engineering using the bacterial RNA-guided CRISPR-Cas9 system in animals and plants is transforming biology. We review the history of CRISPR (clustered regularly interspaced palindromic repeat) biology from its initial discovery through the elucidation of the CRISPR-Cas9 enzyme mechanism, which has set the stage for remarkable developments using this technology to modify, regulate, or mark genomic loci in a wide variety of cells and organisms from all three domains of life. These results highlight a new era in which genomic manipulation is no longer a bottleneck to experiments, paving the way toward fundamental discoveries in biology, with applications in all branches of biotechnology, as well as strategies for human therapeutics.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Doudna, J. A. and Charpentier, E.},
doi = {10.1126/science.1258096},
eprint = {NIHMS150003},
isbn = {1095-9203 (Electronic) 0036-8075 (Linking)},
issn = {0036-8075},
journal = {Science},
number = {6213},
pages = {1258096--1258096},
pmid = {25430774},
title = {{The new frontier of genome engineering with CRISPR-Cas9}},
url = {http://www.sciencemag.org/cgi/doi/10.1126/science.1258096},
volume = {346},
year = {2014}
}
@article{Sancak2007,
abstract = {The heterotrimeric mTORC1 protein kinase nucleates a signaling network that promotes cell growth in response to insulin and becomes constitutively active in cells missing the TSC1 or TSC2 tumor suppressors. Insulin stimulates the phosphorylation of S6K1, an mTORC1 substrate, but it is not known how mTORC1 kinase activity is regulated. We identify PRAS40 as a raptor-interacting protein that binds to mTORC1 in insulin-deprived cells and whose in vitro interaction with mTORC1 is disrupted by high salt concentrations. PRAS40 inhibits cell growth, S6K1 phosphorylation, and rheb-induced activation of the mTORC1 pathway, and in vitro it prevents the great increase in mTORC1 kinase activity induced by rheb1-GTP. Insulin stimulates Akt/PKB-mediated phosphorylation of PRAS40, which prevents its inhibition of mTORC1 in cells and in vitro. We propose that the relative strengths of the rheb- and PRAS40-mediated inputs to mTORC1 set overall pathway activity and that insulin activates mTORC1 through the coordinated regulation of both. {\textcopyright} 2007 Elsevier Inc. All rights reserved.},
author = {Sancak, Yasemin and Thoreen, Carson C. and Peterson, Timothy R. and Lindquist, Robert A. and Kang, Seong A. and Spooner, Eric and Carr, Steven A. and Sabatini, David M.},
doi = {10.1016/j.molcel.2007.03.003},
isbn = {1097-2765 (Print)},
issn = {10972765},
journal = {Molecular Cell},
keywords = {SIGNALING},
pmid = {17386266},
title = {{PRAS40 Is an Insulin-Regulated Inhibitor of the mTORC1 Protein Kinase}},
year = {2007}
}
@article{Doudna2014a,
abstract = {The advent of facile genome engineering using the bacterial RNA-guided CRISPR-Cas9 system in animals and plants is transforming biology. We review the history of CRISPR (clustered regularly interspaced palindromic repeat) biology from its initial discovery through the elucidation of the CRISPR-Cas9 enzyme mechanism, which has set the stage for remarkable developments using this technology to modify, regulate, or mark genomic loci in a wide variety of cells and organisms from all three domains of life. These results highlight a new era in which genomic manipulation is no longer a bottleneck to experiments, paving the way toward fundamental discoveries in biology, with applications in all branches of biotechnology, as well as strategies for human therapeutics.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Doudna, J. A. and Charpentier, E.},
doi = {10.1126/science.1258096},
eprint = {NIHMS150003},
isbn = {1095-9203 (Electronic) 0036-8075 (Linking)},
issn = {0036-8075},
journal = {Science},
number = {6213},
pages = {1258096--1258096},
pmid = {25430774},
title = {{The new frontier of genome engineering with CRISPR-Cas9}},
url = {http://www.sciencemag.org/cgi/doi/10.1126/science.1258096},
volume = {346},
year = {2014}
}
@article{Wrzodek2013a,
abstract = {BACKGROUND: The KEGG PATHWAY database provides a plethora of pathways for a diversity of organisms. All pathway components are directly linked to other KEGG databases, such as KEGG COMPOUND or KEGG REACTION. Therefore, the pathways can be extended with an enormous amount of information and provide a foundation for initial structural modeling approaches. As a drawback, KGML-formatted KEGG pathways are primarily designed for visualization purposes and often omit important details for the sake of a clear arrangement of its entries. Thus, a direct conversion into systems biology models would produce incomplete and erroneous models.$\backslash$n$\backslash$nRESULTS: Here, we present a precise method for processing and converting KEGG pathways into initial metabolic and signaling models encoded in the standardized community pathway formats SBML (Levels 2 and 3) and BioPAX (Levels 2 and 3). This method involves correcting invalid or incomplete KGML content, creating complete and valid stoichiometric reactions, translating relations to signaling models and augmenting the pathway content with various information, such as cross-references to Entrez Gene, OMIM, UniProt ChEBI, and many more.Finally, we compare several existing conversion tools for KEGG pathways and show that the conversion from KEGG to BioPAX does not involve a loss of information, whilst lossless translations to SBML can only be performed using SBML Level 3, including its recently proposed qualitative models and groups extension packages.$\backslash$n$\backslash$nCONCLUSIONS: Building correct BioPAX and SBML signaling models from the KEGG database is a unique characteristic of the proposed method. Further, there is no other approach that is able to appropriately construct metabolic models from KEGG pathways, including correct reactions with stoichiometry. The resulting initial models, which contain valid and comprehensive SBML or BioPAX code and a multitude of cross-references, lay the foundation to facilitate further modeling steps.},
author = {Wrzodek, Clemens and B{\"{u}}chel, Finja and Ruff, Manuel and Dr{\"{a}}ger, Andreas and Zell, Andreas},
doi = {10.1186/1752-0509-7-15},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Wrzodek et al. - 2013 - Precise generation of systems biology models from KEGG pathways(2).pdf:pdf},
isbn = {1752-0509 (Electronic)$\backslash$r1752-0509 (Linking)},
issn = {17520509},
journal = {BMC Systems Biology},
keywords = {BioPAX,Comparison,Converter,KEGG,KGML,Modeling,Qualitative modeling,Quantitative modeling,SBML,Systems biology},
pmid = {23433509},
title = {{Precise generation of systems biology models from KEGG pathways}},
volume = {7},
year = {2013}
}
@article{Gibson2009,
abstract = {We describe an isothermal, single-reaction method for assembling multiple overlapping DNA molecules by the concerted action of a 5' exonuclease, a DNA polymerase and a DNA ligase. First we recessed DNA fragments, yielding single-stranded DNA overhangs that specifically annealed, and then covalently joined them. This assembly method can be used to seamlessly construct synthetic and natural genes, genetic pathways and entire genomes, and could be a useful molecular engineering tool.},
author = {Gibson, Daniel G and Young, Lei and Chuang, Ray-Yuan and Venter, J Craig and Hutchison, Clyde A and Smith, Hamilton O},
doi = {10.1038/nmeth.1318},
isbn = {1548-7105 (Electronic)$\backslash$r1548-7091 (Linking)},
issn = {1548-7091},
journal = {Nature Methods},
number = {5},
pages = {343--345},
pmid = {19363495},
title = {{Enzymatic assembly of DNA molecules up to several hundred kilobases}},
url = {http://www.nature.com/doifinder/10.1038/nmeth.1318},
volume = {6},
year = {2009}
}
@article{Rodriguez-martinez2018,
author = {Rodriguez-martinez, Author Andrea and Ayala, Rafael and Posma, Joram M and Neves, Ana L and An-, Maryam and Nicholson, Jeremy K and Dumas, Marc-emmanuel and Rodriguez-martinez, Maintainer Andrea and Ayala, Rafael},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Rodriguez-martinez et al. - 2018 - Package ‘ MetaboSignal '.pdf:pdf},
title = {{Package ‘ MetaboSignal '}},
year = {2018}
}
@article{Ma2005,
abstract = {Tuberous sclerosis (TSC) is a tumor syndrome caused by mutation in TSC1 or TSC2 genes. TSC tumorigenesis is not always accompanied by loss of heterozygosity (LOH). Recently, extracellular signal-regulated kinase (Erk) has been found activated in TSC lesions lacking TSC1 or TSC2 LOH. Here, we show that Erk may play a critical role in TSC progression through posttranslational inactivation of TSC2. Erk-dependent phosphorylation leads to TSC1-TSC2 dissociation and markedly impairs TSC2 ability to inhibit mTOR signaling, cell proliferation, and oncogenic transformation. Importantly, expression of an Erk nonphosphorylatable TSC2 mutant in TSC2+/-tumor cells where Erk is constitutively activated blocks tumorigenecity in vivo, while wild-type TSC2 is ineffective. Our findings position the Ras/MAPK pathway upstream of the TSC complex and suggest that Erk may modulate mTOR signaling and contribute to disease progression through phosphorylation and inactivation of TSC2. Copyright {\textcopyright}2005 by Elsevier Inc.},
author = {Ma, Li and Chen, Zhenbang and Erdjument-Bromage, Hediye and Tempst, Paul and Pandolfi, Pier Paolo},
doi = {10.1016/j.cell.2005.02.031},
isbn = {0092-8674 (Print)},
issn = {00928674},
journal = {Cell},
pmid = {15851026},
title = {{Phosphorylation and functional inactivation of TSC2 by Erk: Implications for tuberous sclerosis and cancer pathogenesis}},
year = {2005}
}
@article{Hall2008,
abstract = {Target of rapamycin (TOR) is a highly conserved serine/threonine kinase that controls cell growth and metabolism in response to nutrients, growth factors, cellular energy, and stress. TOR, which was originally discovered in yeast, is conserved in all eukaryotes including plants, worms, flies, and mammals. The discovery of TOR led to a fundamental change in how we think about cell growth. It is not a spontaneous process that just happens when building blocks (nutrients) are available, but rather a highly regulated, plastic process controlled by TOR-dependent signaling pathways. TOR is found in 2 structurally and functionally distinct multiprotein complexes, TORC1 and TORC2. The 2 TOR complexes, like TOR itself, are highly conserved. Mammalian TORC1 (mTORC1) is rapamycin sensitive and contains mTOR, raptor, and mLST8. TORC1 in yeast and mammals mediates temporal control of cell growth by regulating several cellular processes, including translation, transcription, ribosome biogenesis, nutrient transport, and autophagy. mTORC2 is rapamycin insensitive and contains mTOR, rictor, mSIN1, PRR5, and mLST8. TORC2 in yeast and mammals mediates spatial control of cell growth by regulating the actin cytoskeleton. Thus, the 2 TOR complexes constitute an ancestral signaling network conserved throughout eukaryotic evolution to control the fundamental process of cell growth. As a central controller of cell growth, TOR plays a key role in development and aging and has been implicated in disorders such as cancer, cardiovascular disease, obesity, and diabetes. The challenge now is to understand the role of mTOR signaling to coordinate and integrate overall body growth in multicellular organisms. {\textcopyright} 2008.},
author = {Hall, M. N.},
doi = {10.1016/j.transproceed.2008.10.009},
isbn = {1010891096},
issn = {00411345},
journal = {Transplantation Proceedings},
pmid = {19100909},
title = {{mTOR-What Does It Do?}},
year = {2008}
}
@misc{Hohmann2002,
abstract = {The yeast Saccharomyces cerevisiae (baker's yeast or budding yeast) is an excellent eukaryotic model system for cellular biology with a well-explored, completely sequenced genome. Yeast cells possess robust systems for osmotic adaptation. Central to the response to high osmolarity is the HOG pathway, one of the best-explored MAP kinase pathways. This pathway controls via different transcription factors the expression of more than 150 genes. In addition, osmotic responses are also controlled by protein kinase A via a general stress response pathway and by presently unknown signaling systems. The HOG pathway partially controls expression of genes encoding enzymes in glycerol production. Glycerol is the main yeast osmolyte, and its production is essential for growth in a high osmolarity medium. Upon hypo-osmotic shock, yeast cells transiently stimulate another MAP kinase pathway, the so-called PKC pathway, which appears to orchestrate the assembly of the cell surface and the cell wall. In addition, yeast cells show signs of a regulated volume decrease by rapidly exporting glycerol through Fps1p. This unusual MIP channel is gated by osmotic changes and thereby plays a key role in controlling the intracellular osmolyte content. Yeast cells also possess two aquaporins, Aqy1p and Aqy2p. The production of both proteins is strictly regulated, suggesting that these water channels play very specific roles in yeast physiology. Aqy1p appears to be developmentally regulated. Given the strong yeast research community and the excellent tools of genetics and functional genomics available, we expect yeast to be the best-explored cellular organism for several years ahead, and osmotic responses are a focus of interest for numerous yeast researchers. ?? 2002 Elsevier Science (USA).},
author = {Hohmann, Stefan},
booktitle = {International Review of Cytology},
doi = {10.1016/S0074-7696(02)15008-X},
isbn = {00747696 (ISSN)},
issn = {00747696},
keywords = {Adaptation,Gene expression,Glycerol,MAP kinase signaling,Osmotic shock,Transport,Yeast},
pages = {149--187},
pmid = {11952227},
title = {{Osmotic adaptation in yeast-control of the yeast osmolyte system}},
volume = {215},
year = {2002}
}
@article{Buchel2013a,
abstract = {BACKGROUND: Systems biology projects and omics technologies have led to a growing number of biochemical pathway models and reconstructions. However, the majority of these models are still created de novo, based on literature mining and the manual processing of pathway data.$\backslash$n$\backslash$nRESULTS: To increase the efficiency of model creation, the Path2Models project has automatically generated mathematical models from pathway representations using a suite of freely available software. Data sources include KEGG, BioCarta, MetaCyc and SABIO-RK. Depending on the source data, three types of models are provided: kinetic, logical and constraint-based. Models from over 2 600 organisms are encoded consistently in SBML, and are made freely available through BioModels Database at http://www.ebi.ac.uk/biomodels-main/path2models. Each model contains the list of participants, their interactions, the relevant mathematical constructs, and initial parameter values. Most models are also available as easy-to-understand graphical SBGN maps.$\backslash$n$\backslash$nCONCLUSIONS: To date, the project has resulted in more than 140 000 freely available models. Such a resource can tremendously accelerate the development of mathematical models by providing initial starting models for simulation and analysis, which can be subsequently curated and further parameterized.},
archivePrefix = {arXiv},
arxivId = {1307.7005},
author = {B{\"{u}}chel, Finja and Rodriguez, Nicolas and Swainston, Neil and Wrzodek, Clemens and Czauderna, Tobias and Keller, Roland and Mittag, Florian and Schubert, Michael and Glont, Mihai and Golebiewski, Martin and van Iersel, Martijn and Keating, Sarah and Rall, Matthias and Wybrow, Michael and Hermjakob, Henning and Hucka, Michael and Kell, Douglas B. and M{\"{u}}ller, Wolfgang and Mendes, Pedro and Zell, Andreas and Chaouiya, Claudine and Saez-Rodriguez, Julio and Schreiber, Falk and Laibe, Camille and Dr{\"{a}}ger, Andreas and {Le Nov{\`{e}}re}, Nicolas},
doi = {10.1186/1752-0509-7-116},
eprint = {1307.7005},
file = {:Users/ozlem/Dropbox/papers/Path2Models- large-scale generation of computational models from biochemical pathway maps.pdf:pdf},
isbn = {1752-0509 (Electronic)$\backslash$r1752-0509 (Linking)},
issn = {17520509},
journal = {BMC Systems Biology},
keywords = {Constraint based models,Logical models,Modular rate law,SBGN,SBML},
pmid = {24180668},
title = {{Path2Models: Large-scale generation of computational models from biochemical pathway maps}},
volume = {7},
year = {2013}
}
@article{Gabor2018,
author = {Gabor, Maintainer A},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Gabor - 2018 - Package ‘ CellNOptR '.pdf:pdf},
title = {{Package ‘ CellNOptR '}},
year = {2018}
}
@article{Asghar2015,
author = {Asghar, Uzma and Witkiewicz, Agnieszka K and Turner, Nicholas C and Knudsen, Erik S},
journal = {Nature Reviews Drug Discovery},
month = {jan},
pages = {130},
publisher = {Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.},
title = {{The history and future of targeting cyclin-dependent kinases in cancer therapy}},
url = {https://doi.org/10.1038/nrd4504 http://10.0.4.14/nrd4504 https://www.nature.com/articles/nrd4504{\#}supplementary-information},
volume = {14},
year = {2015}
}
@article{Terfve2012a,
abstract = {BACKGROUND Cells process signals using complex and dynamic networks. Studying how this is performed in a context and cell type specific way is essential to understand signaling both in physiological and diseased situations. Context-specific medium/high throughput proteomic data measured upon perturbation is now relatively easy to obtain but formalisms that can take advantage of these features to build models of signaling are still comparatively scarce. RESULTS Here we present CellNOptR, an open-source R software package for building predictive logic models of signaling networks by training networks derived from prior knowledge to signaling (typically phosphoproteomic) data. CellNOptR features different logic formalisms, from Boolean models to differential equations, in a common framework. These different logic model representations accommodate state and time values with increasing levels of detail. We provide in addition an interface via Cytoscape (CytoCopteR) to facilitate use and integration with Cytoscape network-based capabilities. CONCLUSIONS Models generated with this pipeline have two key features. First, they are constrained by prior knowledge about the network but trained to data. They are therefore context and cell line specific, which results in enhanced predictive and mechanistic insights. Second, they can be built using different logic formalisms depending on the richness of the available data. Models built with CellNOptR are useful tools to understand how signals are processed by cells and how this is altered in disease. They can be used to predict the effect of perturbations (individual or in combinations), and potentially to engineer therapies that have differential effects/side effects depending on the cell type or context.},
author = {Terfve, Camille and Cokelaer, Thomas and Henriques, David and MacNamara, Aidan and Goncalves, Emanuel and Morris, Melody K. and van Iersel, Martijn and Lauffenburger, Douglas A. and Saez-Rodriguez, Julio},
doi = {10.1186/1752-0509-6-133},
isbn = {1752-0509},
issn = {17520509},
journal = {BMC Systems Biology},
keywords = {Logic modeling,Perturbation data,Phosphoproteomics,Signaling networks,Systems biology},
pmid = {23079107},
title = {{CellNOptR: A flexible toolkit to train protein signaling networks to data using multiple logic formalisms}},
year = {2012}
}
@article{Niwa1998,
abstract = {We report the first on-line electrochemical sensor for the continuous measurement of gamma-aminobutyric acid (GABA), which is a well-known inhibitory neurotransmitter in the nervous system. The sensor is composed of a glutamate oxidase (GluOx) and catalase immobilized small-volume enzymatic reactor and a glassy carbon (GC) electrode modified with a top layer film consisting of gabase and GluOx coimmobilized bovine serum albumin and an Ospoly(vinylpyrridine) bottom layer film containing horseradish peroxidase. The response of the sensor depends on the alpha-ketoglutarate concentration and is almost saturated when its concentration is 100 times higher than GABA. The sensor exhibits a sensitivity of 1.56 nA/microM for GABA under optimized conditions and shows almost no response when 10 microM glutamate is continuously injected. A detection limit of 0.1 microM is obtained with a linear range of 0.1-10 microM. GABA can be measured in the absence of alpha-ketoglutarate when there is L-glutamate in the sample solution, which is a typical condition for the extracellular measurement of cultured nerve cells.},
author = {Niwa, Osamu and Kurita, Ryoji and Horiuchi, Tsutomu and Torimitsu, Keiichi},
doi = {10.1021/ac970740z},
issn = {0003-2700},
journal = {Analytical Chemistry},
number = {1},
pages = {89--93},
pmid = {9435468},
title = {{Small-Volume On-Line Sensor for Continuous Measurement of $\gamma$-Aminobutyric Acid}},
url = {http://pubs.acs.org/doi/abs/10.1021/ac970740z},
volume = {70},
year = {1998}
}
@article{Kim2016,
author = {Kim, Jiyoung and Oh, Junsang and Sung, Gi Ho},
doi = {10.3389/fmicb.2016.00732},
issn = {1664302X},
journal = {Frontiers in Microbiology},
keywords = {1H-nuclear magnetic resonance,Beauveria bassiana,Hog1/MAP kinase,Hyperosmotic stress,Saccharomyces cerevisiae},
number = {MAY},
title = {{MAP kinase Hog1 regulates metabolic changes induced by hyperosmotic stress}},
volume = {7},
year = {2016}
}
@misc{Kaznessis2007,
abstract = {Synthetic biological engineering is emerging from biology as a distinct discipline based on quantification. The technologies propelling synthetic biology are not new, nor is the concept of designing novel biological molecules. What is new is the emphasis on system behavior. The objective is the design and construction of new biological devices and systems to deliver useful applications. Numerous synthetic gene circuits have been created in the past decade, including bistable switches, oscillators, and logic gates, and possible applications abound, including biofuels, detectors for biochemical and chemical weapons, disease diagnosis, and gene therapies. More than fifty years after the discovery of the molecular structure of DNA, molecular biology is mature enough for real quantification that is useful for biological engineering applications, similar to the revolution in modeling in chemistry in the 1950s. With the excitement that synthetic biology is generating, the engineering and biological science communities appear remarkably willing to cross disciplinary boundaries toward a common goal.},
author = {Kaznessis, Yiannis N.},
booktitle = {BMC Systems Biology},
doi = {10.1186/1752-0509-1-47},
isbn = {1752-0509 (Electronic) 1752-0509 (Linking)},
issn = {17520509},
pmid = {17986347},
title = {{Models for synthetic biology}},
year = {2007}
}
@inproceedings{Hu2017,
abstract = {People often refer to entities in an image in terms of their relationships with other entities. For example, "the black cat sitting under the table" refers to both a "black cat" entity and its relationship with another "table" entity. Understanding these relationships is essential for interpreting and grounding such natural language expressions. Most prior work focuses on either grounding entire referential expressions holistically to one region, or localizing relationships based on a fixed set of categories. In this paper we instead present a modular deep architecture capable of analyzing referential expressions into their component parts, identifying entities and relationships mentioned in the input expression and grounding them all in the scene. We call this approach Compositional Modular Networks (CMNs): a novel architecture that learns linguistic analysis and visual inference end-to-end. Our approach is built around two types of neural modules that inspect local regions and pairwise interactions between regions. We evaluate CMNs on multiple referential expression datasets, outperforming state-of-the-art approaches on all tasks.},
archivePrefix = {arXiv},
arxivId = {1611.09978},
author = {Hu, Ronghang and Rohrbach, Marcus and Andreas, Jacob and Darrell, Trevor and Saenko, Kate},
booktitle = {Proceedings - 30th IEEE Conference on Computer Vision and Pattern Recognition, CVPR 2017},
doi = {10.1109/CVPR.2017.470},
eprint = {1611.09978},
isbn = {9781538604571},
issn = {10638210},
pmid = {26134736},
title = {{Modeling relationships in referential expressions with compositional modular networks}},
year = {2017}
}
@article{Chowdhury2014,
abstract = {A major mRNA decay pathway in eukaryotes is initiated by deadenylation followed by decapping of the oligoadenylated mRNAs and subsequent 5'-to-3' exonucleolytic degradation of the capless mRNA. In this pathway, decapping is a rate-limiting step that requires the hetero-octameric Lsm1-7-Pat1 complex to occur at normal rates in vivo. This complex is made up of the seven Sm-like proteins, Lsm1 through Lsm7, and the Pat1 protein. It binds RNA and has a unique binding preference for oligoadenylated RNAs over polyadenylated RNAs. Such binding ability is crucial for its mRNA decay function in vivo. In order to determine the contribution of Pat1 to the function of the Lsm1-7-Pat1 complex, we compared the RNA binding properties of the Lsm1-7 complex purified from pat1$\Delta$ cells and purified Pat1 fragments with that of the wild-type Lsm1-7-Pat1 complex. Our studies revealed that both the Lsm1-7 complex and purified Pat1 fragments have very low RNA binding activity and are impaired in the ability to recognize the oligo(A) tail on the RNA. However, reconstitution of the Lsm1-7-Pat1 complex from these components restored these abilities. We also observed that Pat1 directly contacts RNA in the context of the Lsm1-7-Pat1 complex. These studies suggest that the unique RNA binding properties and the mRNA decay function of the Lsm1-7-Pat1 complex involve cooperation of residues from both Pat1 and the Lsm1-7 ring. Finally our studies also revealed that the middle domain of Pat1 is essential for the interaction of Pat1 with the Lsm1-7 complex in vivo.},
author = {Chowdhury, Ashis and Kalurupalle, Swathi and Tharun, Sundaresan},
doi = {10.1261/rna.045252.114},
isbn = {1355-8382},
issn = {1355-8382},
journal = {RNA},
number = {9},
pages = {1465--1475},
pmid = {25035297},
title = {{Pat1 contributes to the RNA binding activity of the Lsm1-7–Pat1 complex}},
volume = {20},
year = {2014}
}
@article{Glaab2017,
abstract = {Parkinson's disease (PD) is a prime example of a complex and heterogeneous disorder, characterized by multifaceted and varied motor-and non-motor symptoms and different possible interplays of genetic and environmental risk factors. While investigations of individual PD-causing mutations and risk factors in isolation are providing important insights to improve our understanding of the molecular mechanisms behind PD, there is a growing consensus that a more complete understanding of these mechanisms will require an integrative modeling of multifactorial disease-associated perturbations in molecular networks. Identifying and interpreting the combinatorial effects of multiple PD-associated molecular changes may pave the way towards an earlier and reliable diagnosis and more effective therapeutic interventions. This review provides an overview of computational systems biology approaches developed in recent years to study multifactorial molecular alterations in complex disorders, with a focus on PD research applications. Strengths and weaknesses of different cellular pathway and network analyses, and multivariate machine learning techniques for investigating PD-related omics data are discussed, and strategies proposed to exploit the synergies of multiple biological knowledge and data sources. A final outlook provides an overview of specific challenges and possible next steps for translating systems biology findings in PD to new omics-based diagnostic tools and targeted, drug-based therapeutic approaches.},
author = {Glaab, Enrico},
doi = {10.1007/s00441-017-2734-5},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Glaab - 2017 - Computational systems biology approaches for Parkinson's disease.pdf:pdf},
issn = {14320878},
journal = {Cell and Tissue Research},
keywords = {Bioinformatics,Network analysis,Parkinson's disease,Pathway analysis,Systems biology},
number = {Knudson 1971},
pages = {1--19},
pmid = {29185073},
publisher = {Cell and Tissue Research},
title = {{Computational systems biology approaches for Parkinson's disease}},
year = {2017}
}
@article{Research2009,
abstract = {The mechanisms of the control and activity of the autophagy-lysosomal protein degradation machinery is emerging as an important theme for neurodevelopment and neurodegeneration. However, the underlying regulatory and functional networks of known genes controlling autophagy and lysosomal function and their role in disease are relatively unexplored. We performed a systems biology-based integrative computational analysis to study the interactions between molecular components and to develop models for regulation and function of genes involved in autophagy and lysosomal function. Specifically, we analyzed transcriptional and microRNA-based posttranscriptional regulation of these genes and performed functional enrichment analyses to understand their involvement in nervous system-related diseases and phenotypes. Transcriptional regulatory network analysis showed that binding sites for transcription factors, SREBP1, USF, AP-1 and NFE2, are common among autophagy and lysosomal genes. MicroRNA enrichment analysis revealed miR-130, 98, 124, 204 and 142 as the putative posttranscriptional regulators of the autophagy-lysosomal pathway genes. Pathway enrichment analyses revealed that the mTOR and insulin signaling pathways are important in the regulation of genes involved in autophagy. In addition, we found that glycosaminoglycan and glycosphingolipid pathways also make a major contribution to lysosomal gene regulation. The analysis confirmed the known contribution of the autophagy-lysosomal genes to Alzheimer and Parkinson diseases and also revealed potential involvement in tuberous sclerosis, neuronal ceroid-lipofuscinoses, sepsis, and lung, liver and prostatic neoplasms. To further probe the impact of autophagy-lysosomal gene deficits on neurologically-linked phenotypes, we also mined the mouse knockout phenotype data for the autophagy-lysosomal genes and found them to be highly predictive of nervous system dysfunction. Overall this study demonstrates the utility of systems biology-based approaches for understanding the autophagy-lysosomal pathways and gaining additional insights into the potential impact of defects in these complex biological processes.},
archivePrefix = {arXiv},
arxivId = {arXiv:1011.1669v3},
author = {Research, Who Alliance for Health Policy and Systems},
doi = {10.1155/2010/268925},
eprint = {arXiv:1011.1669v3},
isbn = {9789241563},
issn = {16878035},
journal = {Autophagy},
keywords = {Health systems strengthening,Systems thinking},
pmid = {21331364},
title = {{Systems thinking for health systems strengthening}},
year = {2009}
}
@article{Kitano2005,
abstract = {With the increased interest in understanding biological networks, such as protein-protein interaction networks and gene regulatory networks, methods for representing and communicating such networks in both human- and machine-readable form have become increasingly important. Although there has been significant progress in machine-readable representation of networks, as exemplified by the Systems Biology Mark-up Language (SBML) (http://www.sbml.org) issues in human-readable representation have been largely ignored. This article discusses human-readable diagrammatic representations and proposes a set of notations that enhances the formality and richness of the information represented. The process diagram is a fully state transition-based diagram that can be translated into machine-readable forms such as SBML in a straightforward way. It is supported by CellDesigner, a diagrammatic network editing software (http://www.celldesigner.org/), and has been used to represent a variety of networks of various sizes (from only a few components to several hundred components).},
author = {Kitano, Hiroaki and Funahashi, Akira and Matsuoka, Yukiko and Oda, Kanae},
doi = {10.1038/nbt1111},
file = {:Users/ozlem/Desktop/papers/Kitano2005.pdf:pdf},
isbn = {1087-0156 (Print)$\backslash$r1087-0156 (Linking)},
issn = {10870156},
journal = {Nature Biotechnology},
number = {8},
pages = {961--966},
pmid = {16082367},
title = {{Using process diagrams for the graphical representation of biological networks}},
volume = {23},
year = {2005}
}
@article{Burgess2003,
abstract = {Recent crystallographic studies have provided significant new insight into how receptor tyrosine kinases from the EGF receptor or ErbB family are regulated by their growth factor ligands. EGF receptor dimerization is mediated by a unique dimerization arm, which becomes exposed only after a dramatic domain rearrangement is promoted by growth factor binding. ErbB2, a family member that has no ligand, has its dimerization arm constitutively exposed, and this explains several of its unique properties. We outline a mechanistic view of ErbB receptor homo- and heterodimerization, which suggests new approaches for interfering with these processes when they are implicated in human cancers.},
author = {Burgess, Antony W. and Cho, Hyun Soo and Eigenbrot, Charles and Ferguson, Kathryn M. and Garrett, Thomas P.J. and Leahy, Daniel J. and Lemmon, Mark A. and Sliwkowski, Mark X. and Ward, Colin W. and Yokoyama, Shigeyuki},
doi = {10.1016/S1097-2765(03)00350-2},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Burgess et al. - 2003 - An open-and-shut case Recent insights into the activation of EGFErbB receptors.pdf:pdf},
isbn = {1097-2765 (Print)$\backslash$n1097-2765 (Linking)},
issn = {10972765},
journal = {Molecular Cell},
number = {3},
pages = {541--552},
pmid = {14527402},
title = {{An open-and-shut case? Recent insights into the activation of EGF/ErbB receptors}},
volume = {12},
year = {2003}
}
@article{Huang2004,
abstract = {Genome-scale molecular networks, including protein interaction and gene regulatory networks, have taken centre stage in the investigation of the burgeoning disciplines of systems biology and biocomplexity. What do networks tell us? Some see in networks simply the comprehensive, detailed description of all cellular pathways, others seek in networks simple, higher-order qualities that emerge from the collective action of the individual pathways. This paper discusses networks from an encompassing category of thinking that will hopefully help readers to bridge the gap between these polarised viewpoints. Systems biology so far has emphasised the characterisation of large pathway maps. Now one has to ask: where is the actual biology in 'systems biology'? As structures midway between genome and phenome, and by serving as an 'extended genotype' or an 'elementary phenotype', molecular networks open a new window to the study of evolution and gene function in complex living systems. For the study of evolution, features in network topology offer a novel starting point for addressing the old debate on the relative contributions of natural selection versus intrinsic constraints to a particular trait. To study the function of genes, it is necessary not only to see them in the context of gene networks, but also to reach beyond describing network topology and to embrace the global dynamics of networks that will reveal higher-order, collective behaviour of the interacting genes. This will pave the way to understanding how the complexity of genome-wide molecular networks collapses to produce a robust whole-cell behaviour that manifests as tightly-regulated switching between distinct cell fates - the basis for multicellular life.},
author = {Huang, Sui},
doi = {10.1093/bfgp/2.4.279},
file = {:Users/ozlem/Dropbox/papers/Biological Networks/279.pdf:pdf},
isbn = {1473-9550 (Print)$\backslash$r1473-9550 (Linking)},
issn = {14739550},
journal = {Briefings in Functional Genomics and Proteomics},
keywords = {Adaptation,Attractors,Biocomplexity,Genetic networks,Intrinsic constraints,Systems biology},
pmid = {15163364},
title = {{Back to the biology in systems biology: What can we learn from biomolecular networks?}},
year = {2004}
}
@article{Quantin1988,
author = {Quantin, B{\'{e}}atrice and Breathnach, Richard},
journal = {Nature},
month = {aug},
pages = {538},
publisher = {Nature Publishing Group},
title = {{Epidermal growth factor stimulates transcription of the c-jun proto-oncogene in rat fibroblasts}},
url = {https://doi.org/10.1038/334538a0 http://10.0.4.14/334538a0},
volume = {334},
year = {1988}
}
@article{Lin2009,
abstract = {The MutT/Nudix superfamily proteins repair DNA damage and play a role in human health and disease. In this study, we examined two different cases of double MutT/Nudix domain-containing proteins from eukaryotes and prokaryotes. Firstly, these double domain proteins were discovered in Drosophila, but only single Nudix domain proteins were found in other animals. The phylogenetic tree was constructed based on the protein sequence of Nudix{\_}N and Nudix{\_}C from Drosophila, and Nudix from other animals. The phylogenetic analysis suggested that the double Nudix domain proteins might have undergone a gene duplication-speciation-fusion process. Secondly, two genes of the MutT family, DR0004 and DR0329, were fused by two mutT gene segments and formed double MutT domain protein genes in Deinococcus radiodurans. The evolutionary tree of bacterial MutT proteins suggested that the double MutT domain proteins in D. radiodurans probably resulted from a gene duplication-fusion event after speciation. Gene duplication-fusion is a basic and important gene innovation mechanism for the evolution of double MutT/Nudix domain proteins. Independent gene duplication-fusion events resulted in similar domain architectures of different double MutT/Nudix domain proteins. ?? 2009 Institute of Genetics and Developmental Biology and the Genetics Society of China.},
author = {Lin, Jun and Hu, Yihuai and Tian, Bing and Hua, Yuejin},
doi = {10.1016/S1673-8527(08)60152-6},
isbn = {1673-8527 (Print)$\backslash$r1673-8527 (Linking)},
issn = {16738527},
journal = {Journal of Genetics and Genomics},
keywords = {DNA repair,Deinococcus,Drosophila,MutT/Nudix superfamily,gene duplication-fusion},
number = {10},
pages = {603--610},
pmid = {19840758},
title = {{Evolution of double MutT/Nudix domain-containing proteins: similar domain architectures from independent gene duplication-fusion events}},
volume = {36},
year = {2009}
}
@article{Giaever2002,
abstract = {Determining the effect of gene deletion is a fundamental approach to understanding gene function. Conventional genetic screens exhibit biases, and genes contributing to a phenotype are often missed. We systematically constructed a nearly complete collection of gene-deletion mutants (96{\%} of annotated open reading frames, or ORFs) of the yeast Saccharomyces cerevisiae. DNA sequences dubbed 'molecular bar codes' uniquely identify each strain, enabling their growth to be analysed in parallel and the fitness contribution of each gene to be quantitatively assessed by hybridization to high-density oligonucleotide arrays. We show that previously known and new genes are necessary for optimal growth under six well-studied conditions: high salt, sorbitol, galactose, pH 8, minimal medium and nystatin treatment. Less than 7{\%} of genes that exhibit a significant increase in messenger RNA expression are also required for optimal growth in four of the tested conditions. Our results validate the yeast gene-deletion collection as a valuable resource for functional genomics.},
archivePrefix = {arXiv},
arxivId = {15334406},
author = {Giaever, Guri and Chu, Angela M. and Ni, Li and Connelly, Carla and Riles, Linda and V{\'{e}}ronneau, Steeve and Dow, Sally and Lucau-Danila, Ankuta and Anderson, Keith and Andr{\'{e}}, Bruno and Arkin, Adam P. and Astromoff, Anna and {El Bakkoury}, Mohamed and Bangham, Rhonda and Benito, Rocio and Brachat, Sophie and Campanaro, Stefano and Curtiss, Matt and Davis, Karen and Deutschbauer, Adam and Entian, Karl-Dieter and Flaherty, Patrick and Foury, Francoise and Garfinkel, David J. and Gerstein, Mark and Gotte, Deanna and G{\"{u}}ldener, Ulrich and Hegemann, Johannes H. and Hempel, Svenja and Herman, Zelek and Jaramillo, Daniel F. and Kelly, Diane E. and Kelly, Steven L. and K{\"{o}}tter, Peter and LaBonte, Darlene and Lamb, David C. and Lan, Ning and Liang, Hong and Liao, Hong and Liu, Lucy and Luo, Chuanyun and Lussier, Marc and Mao, Rong and Menard, Patrice and Ooi, Siew Loon and Revuelta, Jose L. and Roberts, Christopher J. and Rose, Matthias and Ross-Macdonald, Petra and Scherens, Bart and Schimmack, Greg and Shafer, Brenda and Shoemaker, Daniel D. and Sookhai-Mahadeo, Sharon and Storms, Reginald K. and Strathern, Jeffrey N. and Valle, Giorgio and Voet, Marleen and Volckaert, Guido and Wang, Ching-yun and Ward, Teresa R. and Wilhelmy, Julie and Winzeler, Elizabeth A. and Yang, Yonghong and Yen, Grace and Youngman, Elaine and Yu, Kexin and Bussey, Howard and Boeke, Jef D. and Snyder, Michael and Philippsen, Peter and Davis, Ronald W. and Johnston, Mark},
doi = {10.1038/nature00935},
eprint = {15334406},
isbn = {0028-0836},
issn = {0028-0836},
journal = {Nature},
number = {6896},
pages = {387--391},
pmid = {12140549},
title = {{Functional profiling of the Saccharomyces cerevisiae genome}},
url = {http://www.nature.com/doifinder/10.1038/nature00935},
volume = {418},
year = {2002}
}
@article{Mussel2010a,
abstract = {Motivation: As the study of information processing in living cells moves from individual pathways to complex regulatory networks, mathematical models and simulation become indispensable tools for analyzing the complex behavior of such networks and can provide deep insights into the functioning of cells. The dynamics of gene expression, for example, can be modeled with Boolean networks (BNs). These are mathematical models of low complexity, but have the advantage of being able to capture essential properties of gene-regulatory networks. However, current implementations of BNs only focus on different sub-aspects of this model and do not allow for a seamless integration into existing preprocessing pipelines. Results: BoolNet efficiently integrates methods for synchronous, asynchronous and probabilistic BNs. This includes reconstructing networks from time series, generating random networks, robustness analysis via perturbation, Markov chain simulations, and identification and visualization of attractors. Availability: The package BoolNet is freely available from the R project at},
author = {M{\"{u}}ssel, Christoph and Hopfensitz, Martin and Kestler, Hans A.},
doi = {10.1093/bioinformatics/btq124},
isbn = {1367-4811 (Linking)},
issn = {13674803},
journal = {Bioinformatics},
pmid = {20378558},
title = {{BoolNet - an R package for generation, reconstruction and analysis of Boolean networks}},
year = {2010}
}
@article{Melas2011,
abstract = {Signalling pathways are the cornerstone on understanding cell function and predicting cell behavior. Recently, logical models of canonical pathways have been optimised with high-throughput phosphoproteomic data to construct cell-type specific pathways. However, less is known on how signalling pathways can be linked to a cellular response such as cell growth, death, cytokine secretion, or transcriptional activity.},
author = {Melas, Ioannis N. and Mitsos, Alexander and Messinis, Dimitris E. and Weiss, Thomas S. and Alexopoulos, Leonidas G.},
doi = {10.1186/1752-0509-5-107},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/1752-0509-5-107.pdf:pdf},
isbn = {1752-0509 (Electronic)$\backslash$r1752-0509 (Linking)},
issn = {17520509},
journal = {BMC Systems Biology},
pmid = {21729292},
title = {{Combined logical and data-driven models for linking signalling pathways to cellular response}},
volume = {5},
year = {2011}
}
@article{Pardo2009,
abstract = {DNA double-strand breaks (DSBs) arise in cells from endogenous and exogenous attacks on the DNA backbone, but also as a direct consequence of replication failures. Proper repair of all these DSBs is essential for genome stability. Repair of broken chromosomes is a challenge for dividing cells that need to distribute equal genetic information to daughter cells. Consequently, eukaryotic organisms have evolved multi-potent and efficient mechanisms to repair DSBs that are primarily divided into two types of pathways: nonhomologous end joining (NHEJ) and homologous recombination (HR). Here we briefly describe how eukaryotic cells sense DSBs and trigger cell cycle arrest to allow repair, and we review the mechanisms of both NHEJ and HR pathways and the choice between them. (Part of a Multi-author Review).},
author = {Pardo, B and G{\'{o}}mez-Gonz{\'{a}}lez, B and Aguilera, A},
doi = {10.1007/s00018-009-8740-3},
isbn = {1420-9071 (Electronic)$\backslash$r1420-682X (Linking)},
issn = {1420-9071},
journal = {Cellular and molecular life sciences : CMLS},
keywords = {Cell Cycle,Cell Cycle: physiology,DNA Breaks, Double-Stranded,DNA Damage,DNA Damage: physiology,DNA Ligases,DNA Ligases: metabolism,DNA Repair,DNA Repair: physiology,DNA Replication,DNA Replication: physiology,Double-Stranded,Genetic,Genetic: physiology,Genomic Instability,Recombination, Genetic,Recombination, Genetic: physiology},
number = {6},
pages = {1039--56},
pmid = {19153654},
title = {{DNA repair in mammalian cells: DNA double-strand break repair: how to fix a broken relationship.}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/19153654},
volume = {66},
year = {2009}
}
@article{Zhang2009,
abstract = {MOTIVATION: KEGG PATHWAY is a service of Kyoto Encyclopedia of Genes and Genomes (KEGG), constructing manually curated pathway maps that represent current knowledge on biological networks in graph models. While valuable graph tools have been implemented in R/Bioconductor, to our knowledge there is currently no software package to parse and analyze KEGG pathways with graph theory.$\backslash$n$\backslash$nRESULTS: We introduce the software package KEGGgraph in R and Bioconductor, an interface between KEGG pathways and graph models as well as a collection of tools for these graphs. Superior to existing approaches, KEGGgraph captures the pathway topology and allows further analysis or dissection of pathway graphs. We demonstrate the use of the package by the case study of analyzing human pancreatic cancer pathway.$\backslash$n$\backslash$nAVAILABILITY: KEGGgraph is freely available at the Bioconductor web site (http://www.bioconductor.org). KGML files can be downloaded from KEGG FTP site (ftp://ftp.genome.jp/pub/kegg/xml).},
author = {Zhang, Jitao David and Wiemann, Stefan},
doi = {10.1093/bioinformatics/btp167},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Zhang, Wiemann - 2009 - KEGGgraph A graph approach to KEGG PATHWAY in R and bioconductor(2).pdf:pdf},
isbn = {1367-4811 (Linking)},
issn = {13674803},
journal = {Bioinformatics},
number = {11},
pages = {1470--1471},
pmid = {19307239},
title = {{KEGGgraph: A graph approach to KEGG PATHWAY in R and bioconductor}},
volume = {25},
year = {2009}
}
@article{Yamamoto2006,
annote = {doi: 10.1016/j.cub.2006.04.044},
author = {Yamamoto, Takuya and Ebisuya, Miki and Ashida, Fumito and Okamoto, Kazuo and Yonehara, Shin and Nishida, Eisuke},
doi = {10.1016/j.cub.2006.04.044},
issn = {0960-9822},
journal = {Current Biology},
month = {jun},
number = {12},
pages = {1171--1182},
publisher = {Elsevier},
title = {{Continuous ERK Activation Downregulates Antiproliferative Genes throughout G1 Phase to Allow Cell-Cycle Progression}},
url = {https://doi.org/10.1016/j.cub.2006.04.044},
volume = {16},
year = {2006}
}
@article{Cokelaer2014,
archivePrefix = {arXiv},
arxivId = {arXiv:1412.6386v1},
author = {Cokelaer, Thomas and Saez-rodriguez, Julio},
eprint = {arXiv:1412.6386v1},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Cokelaer, Saez-rodriguez - 2014 - Using Python to Dive into Signalling Data with CellNOpt and BioServices.pdf:pdf},
number = {Euroscipy},
pages = {35--42},
title = {{Using Python to Dive into Signalling Data with CellNOpt and BioServices}},
year = {2014}
}
@article{Manning2002,
abstract = {The S/T-protein kinases activated by phosphoinositide 3-kinase (PI3K) regulate a myriad of cellular processes. Here, we show that an approach using a combination of biochemistry and bioinformatics can identify substrates of these kinases. This approach identifies the tuberous sclerosis complex-2 gene product, tuberin, as a potential target of Akt/PKB. We demonstrate that, upon activation of PI3K, tuberin is phosphorylated on consensus recognition sites for PI3K-dependent S/T kinases. Moreover, Akt/PKB can phosphorylate tuberin in vitro and in vivo. We also show that S939 and T1462 of tuberin are PI3K-regulated phosphorylation sites and that T1462 is constitutively phosphorylated in PTEN-/- tumor-derived cell lines. Finally, we find that a tuberin mutant lacking the major PI3K-dependent phosphorylation sites can block the activation of S6K1, suggesting a means by which the PI3K-Akt pathway regulates S6K1 activity.},
author = {Manning, Brendan D. and Tee, Andrew R. and Logsdon, M. Nicole and Blenis, John and Cantley, Lewis C.},
doi = {10.1016/S1097-2765(02)00568-3},
isbn = {1097-2765},
issn = {10972765},
journal = {Molecular Cell},
pmid = {12150915},
title = {{Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/Akt pathway}},
year = {2002}
}
@article{Didion1996,
abstract = {Branched-chain amino acid uptake in Saccharomyces cerevisiae is mediated by at least three transport systems: the general amino acid permease Gap1p, the branched-chain amino acid permease Bap2p, and one or more so far unknown permeases. Regulation of the transcription of BAP2 is mainly subject to the presence of certain amino acids in the medium. The level of transcription is low during growth on a minimal medium with proline as the sole nitrogen source. As assayed with a lacZ fusion, the level of transcription is slightly higher (3-fold) on a minimal medium with ammonium ions as a nitrogen source, and transcription is induced about 20-fold by addition of leucine (0.2 mM). As little as 10 microM leucine causes a fivefold induction. Addition of (L)-leucine to minimal proline medium, on the other hand, has no effect on BAP2 transcription. The two known permeases for transport of branched-chain amino acids, Gap1p and Bap2p, are thus not active at the same time. The BAP2 promoter contains one or two putative Gcn4p binding sites and one putative Leu3p binding site. None of the three is needed for induction by leucine. Induction of BAP2 transcription by leucine is accompanied by an increase in branched-chain amino acid uptake. This elevation is interpreted to be partly the result of an increased level of the Bap2p permease in the plasma membrane, because deletion of BAP2 slightly decreases the induction of uptake. There is still a leucine-inducible increase in branched-chain amino acid uptake in a delta gap1 delta bap2 strain, indicating that BAP2 shares leucine induction with at least one remaining branched-chain amino acid-transporting permease.},
author = {Didion, T and Grauslund, M and Kielland-Brandt, M C and Andersen, H a},
isbn = {0021-9193},
issn = {0021-9193},
journal = {Journal of bacteriology},
number = {7},
pages = {2025--2029},
pmid = {8606179},
title = {{Amino acids induce expression of BAP2, a branched-chain amino acid permease gene in Saccharomyces cerevisiae.}},
volume = {178},
year = {1996}
}
@article{Shmakov2017,
abstract = {Class 2 CRISPR-Cas systems are characterized by effector modules that consist of a single multidomain protein, such as Cas9 or Cpf1. We designed a computational pipeline for the discovery of novel class 2 variants and used it to identify six new CRISPR-Cas subtypes. The diverse properties of these new systems provide potential for the development of versatile tools for genome editing and regulation. In this Analysis article, we present a comprehensive census of class 2 types and class 2 subtypes in complete and draft bacterial and archaeal genomes, outline evolutionary scenarios for the independent origin of different class 2 CRISPR-Cas systems from mobile genetic elements, and propose an amended classification and nomenclature of CRISPR-Cas.},
author = {Shmakov, Sergey and Smargon, Aaron and Scott, David and Cox, David and Pyzocha, Neena and Yan, Winston and Abudayyeh, Omar O. and Gootenberg, Jonathan S. and Makarova, Kira S. and Wolf, Yuri I. and Severinov, Konstantin and Zhang, Feng and Koonin, Eugene V.},
doi = {10.1038/nrmicro.2016.184},
issn = {1740-1526},
journal = {Nature Reviews Microbiology},
pmid = {28111461},
title = {{Diversity and evolution of class 2 CRISPR–Cas systems}},
url = {http://www.nature.com/doifinder/10.1038/nrmicro.2016.184},
year = {2017}
}
@article{Handorf2012,
abstract = {MOTIVATION: The understanding of the molecular sources for diseases like cancer can be significantly improved by computational models. Recently, Boolean networks have become very popular for modeling signaling and regulatory networks. However, such models rely on a set of Boolean functions that are in general not known. Unfortunately, while detailed information on the molecular interactions becomes available in large scale through electronic databases, the information on the Boolean functions does not become available simultaneously and has to be included manually into the models, if at all known.$\backslash$n$\backslash$nRESULTS: We propose a new Boolean approach which can directly utilize the mechanistic network information available through modern databases. The Boolean function is implicitly defined by the reaction mechanisms. Special care has been taken for the treatment of kinetic features like inhibition. The method has been applied to a signaling model combining the Wnt and MAPK pathway.$\backslash$n$\backslash$nAVAILABILITY: A sample C++ implementation of the proposed method is available for Linux and compatible systems through http://code.google.com/p/libscopes/wiki/Paper2011.},
author = {Handorf, T. and Klipp, E.},
doi = {10.1093/bioinformatics/btr697},
file = {:Users/ozlem/Desktop/papers/btr697.pdf:pdf},
isbn = {1367-4811 (Electronic)$\backslash$n1367-4803 (Linking)},
issn = {13674803},
journal = {Bioinformatics},
number = {4},
pages = {557--563},
pmid = {22199382},
title = {{Modeling mechanistic biological networks: An advanced Boolean approach}},
volume = {28},
year = {2012}
}
@article{Olayioye2000,
abstract = {ErbB family:$\backslash$n$\backslash$nEGF receptor (= ErbB1/HER1)$\backslash$n$\backslash$nErbB2/Neu/HER2$\backslash$n$\backslash$nErbB3/HER3$\backslash$n$\backslash$nErbB4/HER4$\backslash$n$\backslash$n$\backslash$nligands: EGF-related peptide growth factors $\backslash$n$\backslash$n→ receptors form homo- and heterodimers$\backslash$n$\backslash$n$\backslash$n1. intrinsic tyrosine kinase activity of receptors stimulated$\backslash$n$\backslash$n2. autophosphorylation$\backslash$n$\backslash$n3. docking site for signaling molecules$\backslash$n$\backslash$n$\backslash$nErbB2: preferred dimerization partner for other ErbB receptors$\backslash$n$\backslash$n$\backslash$nErbB2 and ErbB3: stimulate mitogenic signaling networks$\backslash$n$\backslash$n→ uncontrolled tumor cell proliferation by a mechanism involving deregulation$\backslash$nof the G1-S transition$\backslash$n$\backslash$n$\backslash$nErbB1, ErbB2: increased proliferation?$\backslash$n$\backslash$n$\backslash$nTherapy:$\backslash$n$\backslash$na monoclonal antibody (4D5) targets extracellular domain of ErbB2:$\backslash$ninhibits in vitro growth of ErbB2 overexpressing tumor cells $\backslash$n$\backslash$nreduction of ErbB2 phorylation, inhibition of receptor signaling (unklar$\backslash$nwie Wirkung ist)$\backslash$n$\backslash$nhumanized version: Herceptin},
archivePrefix = {arXiv},
arxivId = {15334406},
author = {Olayioye, M A and Neve, R M and Lane, H A and Hynes, N E and Alimandi, M. and Romano, A. and Curia, MC. and Muraro, R. and Fedi, P. and Aaronson, SA. and Fiore, PP. Di and Kraus, MH. and Aroian, RV. and Koga, M. and Mendel, JE. and Ohshima, Y. and Sternberg, PW. and Barbacci, EG. and Guarino, BC. and Stroh, JG. and Singleton, DH. and Rosnack, KJ. and Moyer, JD. and Andrews, GC. and Bargmann, CI. and Hung, MC. and Weinberg, RA. and Baselga, J. and Batzer, AG. and Rotin, D. and Urena, JM. and Skolnik, EY. and Schlessinger, J. and Baulida, J. and Kraus, MH. and Alimandi, M. and Fiore, PP. Di and Carpenter, G. and Beerli, RR. and Hynes, NE. and Beerli, RR. and Wels, W. and Hynes, NE. and Beerli, RR. and Graus‐Porta, D. and Woods‐Cook, K. and Chen, X. and Yarden, Y. and Hynes, NE. and Biscardi, JS. and Maa, MC. and Tice, DA. and Cox, ME. and Leu, TH. and Parsons, SJ. and Biscardi, JS. and Tice, DA. and Parsons, SJ. and Bodey, B. and Bodey, B. and Groger, AM. and Luck, JV. and Siegel, SE. and Taylor, CR. and Kaiser, HE. and Britsch, S. and Li, L. and Kirchhoff, S. and Theuring, F. and Brinkmann, V. and Birchmeier, C. and Riethmacher, D. and Busfield, SJ. and Carpenter, G. and Carraway, KL. and Weber, JL. and Unger, MJ. and Ledesma, J. and Yu, N. and Gassmann, M. and Lai, K. and Chang, H. and Riese, DJ. and Gilbert, W. and Stern, DF. and McMahan, UJ. and Chattopadhyay, A. and Vecchi, M. and Ji, Q. and Mernaugh, R. and Carpenter, G. and Cobleigh, MA. and Cohen, BD. and Kiener, PA. and Green, JM. and Foy, L. and Fell, P. and Zhang, K. and Cohen, BD. and Green, JM. and Foy, L. and Fell, HP. and Dankort, DL. and Wang, Z. and Blackmore, V. and Moran, MF. and Muller, WJ. and Darcy, KM. and Zangani, D. and Wolhueter, AL. and Huang, RY. and Vaughan, MM. and Russell, JA. and Ip, MM. and DiGiovanna, MP. and Lerman, MA. and Coffey, RJ. and Muller, WJ. and Cardiff, RD. and Stern, DF. and Downward, J. and Parker, P. and Waterfield, MD. and Elenius, K. and Choi, CJ. and Paul, S. and Santiestevan, E. and Nishi, E. and Klagsbrun, M. and Erickson, SL. and O'Shea, KS. and Ghaboosi, N. and Loverro, L. and Frantz, G. and Bauer, M. and Lu, LH. and Moore, MW. and Fazioli, F. and Minichiello, L. and Matoskova, B. and Wong, WT. and Fiore, PP. Di and Fiddes, RJ. and Campbell, DH. and Janes, PW. and Sivertsen, SP. and Sasaki, H. and Wallasch, C. and Daly, RJ. and Fowler, KJ. and French, AR. and Tadaki, DK. and Niyogi, SK. and Lauffenburger, DA. and Gassmann, M. and Casagranda, F. and Orioli, D. and Simon, H. and Lai, C. and Klein, R. and Lemke, G. and Gilbertson, RJ. and Perry, RH. and Kelly, PJ. and Pearson, ADJ. and Lunee, J. and Graus‐Porta, D. and Beerli, RR. and Hynes, NE. and Graus‐Porta, D. and Beerli, RR. and Daly, JM. and Hynes, NE. and Groenen, LC. and Nice, EC. and Burgess, AW. and Guy, PM. and Platko, JV. and Cantley, LC. and Cerione, RA. and Carraway, KL. and Hackel, PO. and Zwick, E. and Prenzel, N. and Ullrich, A. and Harari, D. and Tzahar, E. and Romano, J. and Shelly, M. and Pierce, JH. and Andrews, GC. and Yarden, Y. and Hazan, R. and Margolis, B. and Dombalagian, M. and Ullrich, A. and Zilberstein, A. and Schlessinger, J. and Heldin, C‐H. and Hennighausen, L. and Robinson, GW. and Hsuan, JJ. and Totty, N. and Waterfield, MD. and Hudziak, RM. and Lewis, GD. and Winget, M. and Fendly, BM. and Shepard, HM. and Ullrich, A. and Hynes, NE. and Stern, DF. and Jannot, CB. and Beerli, RR. and Mason, S. and Gullick, WJ. and Hynes, NE. and Joazeiro, CAP. and Wing, SS. and Huang, HK. and Leverson, JD. and Hunter, T. and Liu, YC. and Jones, FE. and Stern, DF. and Jones, FE. and Welte, T. and Fu, XY. and Stern, DF. and Jones, JY. and Akita, RW. and Sliwkowski, MX. and Karunagaran, D. and Tzahar, E. and Beerli, RR. and Chen, X. and Graus‐Porta, D. and Ratzkin, BJ. and Seger, R. and Hynes, NE. and Yarden, Y. and Katsuura, M. and Tanaka, S. and Keilhack, H. and Tenev, T. and Nyakatura, E. and Godovac‐Zimmermann, J. and Nielsen, L. and Seedorf, K. and Bohmer, FD. and Kokai, Y. and Myers, JN. and Wada, T. and Brown, VI. and LeVea, CM. and Davis, JG. and Dobashi, K. and Greene, MI. and Kramer, R. and Bucay, B. and Kane, DJ. and Martin, LE. and Tarpley, JE. and Theill, LE. and Lane, HA. and Beuvink, I. and Motoyama, AB. and Daly, JM. and Neve, RM. and Hynes, NE. and Lee, KF. and Simon, H. and Chen, H. and Bates, B. and Hung, MC. and Hauser, C. and Lemmon, MA. and Bu, Z. and Ladbury, JE. and Zhou, M. and Pinchasi, D. and Lax, I. and Engelman, DM. and Schlessinger, J. and Lemoine, NR. and Barnes, DM. and Hollywood, DP. and Hughes, CM. and Smith, P. and Dublin, E. and Prigent, SA. and Gullick, WJ. and Hurst, HC. and Lesa, GM. and Sternberg, PW. and Levkowitz, G. and Klapper, LN. and Tzahar, E. and Freywald, A. and Sela, M. and Yarden, Y. and Levkowitz, G. and Lewis, GD. and Figari, I. and Fendly, B. and Wong, WL. and Carter, P. and Gorman, C. and Shepard, HM. and Lewis, GD. and Lofgren, JA. and McMurtrey, AE. and Huijens, A. and Fendly, BM. and Bauer, KD. and Sliwkowski, MX. and Luetteke, NC. and Qiu, TH. and Fenton, SE. and Troyer, KL. and Riedel, RF. and Chang, A. and Lee, DC. and Luttrell, LM. and Daaka, Y. and Lefkowitz, RJ. and Margolis, BL. and Lax, I. and Kris, R. and Dombalagian, M. and Honegger, AM. and Howk, R. and Givol, D. and Ullrich, A. and Schlessinger, J. and Massague, J. and Pandiella, A. and Meisner, H. and Daga, A. and Buxton, J. and Fernandez, B. and Chawla, A. and Banerjee, U. and Czech, MP. and Meyer, D. and Birchmeier, C. and Miettinen, PJ. and Berger, JE. and Meneses, J. and Phung, P. and Pedersen, RA. and Werb, Z. and Derynk, R. and Morris, JK. and Weichun, L. and Hauser, C. and Marchuk, Y. and Getman, D. and Lee, KF. and Neve, RM. and Sutterl{\"{u}}ty, H. and Pullen, N. and Lane, HA. and Daly, JM. and Krek, W. and Hynes, NE. and Ojeda, J. and Ma, YJ. and Okabayashi, Y. and Kido, Y. and Okutani, T. and Sugamoto, Y. and Sakaguchi, K. and Kasuga, M. and Okutani, T. and Okabayashi, Y. and Kido, Y. and Sugimoto, Y. and Sakaguchi, K. and Matuoka, K. and Takenawa, T. and Kasuga, M. and Olayioye, MA. and Graus‐Porta, D. and Beerli, RR. and Rohrer, J. and Gay, B. and Hynes, NE. and Olayioye, MA. and Beuvink, I. and Horsch, K. and Daly, JM. and Hynes, NE. and Paria, BC. and Elenius, K. and Klagsbrun, M. and Dey, SK. and Pegram, MD. and Peles, E. and Yarden, Y. and Pinkas‐Kramarski, R. and Prigent, SA. and Gullick, W. and Rajkumar, T. and Stamp, GWH. and Pandha, HS. and Waxman, J. and Gullick, WJ. and Ricci, A. and Lanfrancone, L. and Chiari, R. and Belardo, G. and Pertica, C. and Natali, PG. and Pelicci, PG. and Segatto, O. and Riese, DJ. and Stern, DF. and Riese, DJ. and van Raaij, TM. and Plowman, GD. and Andrews, GC. and Stern, DF. and Riese, DJ. and Bermingham, Y. and van Raaij, TM. and Buckley, S. and Plowman, GD. and Stern, DF. and Riethmacher, D. and Sonnenberg‐Riethmacher, E. and Brinkmann, V. and Yamaai, T. and Lewin, GR. and Birchneier, C. and Rotin, D. and Sakaguchi, K. and Okabayashi, Y. and Kido, Y. and Kimura, S. and Matsumura, Y. and Inushima, K. and Kasuga, M. and Salomon, DS. and Brandt, R. and Ciardiello, F. and Normanno, N. and Sato, K. and Sato, A. and Aoto, M. and Fukami, Y. and Schroeder, JA. and Lee, DC. and Segatto, O. and Lonardo, F. and Pierce, JH. and Bottaro, DP. and Fiore, PP. Di and Sherr, CJ. and Roberts, JM. and Shoelson, SE. and Sibilia, M. and Wagner, EF. and Sibilia, M. and Steinbach, JP. and Stingl, L. and Aguzzi, A. and Wagner, EF. and Siegel, PM. and Ryan, ED. and Cardiff, RD. and Muller, W. and Slamon, DJ. and Spencer, KSR. and Graus‐Porta, D. and Leng, J. and Hynes, NE. and Klemke, RL. and Stover, DR. and Becker, M. and Liebetanz, J. and Lydon, NB. and Sudol, M. and Tang, CK. and Lippman, ME. and Threadgill, DW. and Torrisi, MR. and Lotti, LV. and Belleudi, F. and Gradini, R. and Salcini, AE. and Confalonieri, S. and Pelicci, PG. and Fiore, PP. Di and Toyoda, H. and Komurasaki, T. and Uchida, D. and Morimoto, S. and Tzahar, E. and Waterman, H. and Chen, X. and Levkowitz, G. and Karunagaran, D. and Lavi, S. and Ratzkin, BJ. and Yarden, Y. and Tzahar, E. and Tzahar, E. and Wallasch, C. and Weiss, FU. and Niederfellner, G. and Jallal, B. and Issing, W. and Ullrich, A. and Walton, GM. and Chen, WS. and Rosenfeld, MG. and Gill, GN. and Wasserman, JD. and Freeman, M. and Waterman, H. and Sabanai, I. and Geiger, B. and Yarden, Y. and Weiner, DB. and Liu, J. and Cohen, JA. and Williams, WV. and Greene, MI. and Weiss, A. and Schlessinger, J. and Wiesen, JF. and Young, P. and Werb, Z. and Cunha, GR. and Xie, W. and Paterson, AJ. and Chin, E. and Nabell, LM. and Kudlow, JE. and Yang, Y. and Spitzer, E. and Meyer, D. and Sachs, M. and Niemann, C. and Hartmann, G. and Weidner, KM. and Birchmeier, C. and Birchmeier, W. and Yokouchi, M. and Kondo, T. and Houghton, A. and Bartkiewicz, M. and Horne, WC. and Zhang, H. and Yoshimura, A. and Baron, R. and Yoon, CH. and Lee, J. and Jongeward, GD. and Sternberg, PW. and Zhang, D. and Zhang, K. and Sun, J. and Liu, N. and Wen, D. and Chang, D. and Thomason, A. and Yoshinaga, SK. and Zrihan‐Licht, S. and Deng, B. and Yarden, Y. and McShan, G. and Keydar, I. and Avraham, H.},
doi = {10.1093/emboj/19.13.3159},
eprint = {15334406},
isbn = {0261-4189 (Print)$\backslash$n0261-4189 (Linking)},
issn = {0261-4189},
journal = {The EMBO journal},
pmid = {10880430},
title = {{The ErbB signaling network: receptor heterodimerization in development and cancer.}},
year = {2000}
}
@article{Lombardi2001,
abstract = {Mutations in RVS161 and RVS167, the two yeast amphiphysin homologs, cause very similar growth phenotypes, a depolarized actin cytoskeleton, and a defect in the internalization step of endocytosis. Rvs161p and Rvs167p have been shown to interact in the two-hybrid system, but their localization in the cell may be different thus raising the question whether the interaction is physiologically relevant. Here we demonstrate that the two proteins function together in vivo. We find that the steady state level of Rvs167p is strongly reduced in an rvs161Delta strain. Similarly, the level of Rvs161p is strongly reduced in an rvs167Delta strain. We demonstrate that these reduced protein levels at steady state are due to a decreased stability of either Rvs protein in the absence of the other protein. Furthermore, we find that the amount and ratio of Rvs161p and Rvs167p are critical parameters for receptor-mediated endocytosis. In addition, by using the two-hybrid system we show that the interaction of Rvs167p with actin is not abolished in an abp1Delta strain suggesting that Abp1p is not essential for this interaction.},
author = {Lombardi, Ruben and Riezman, Howard},
doi = {10.1074/jbc.M008735200},
issn = {00219258},
journal = {Journal of Biological Chemistry},
number = {8},
pages = {6016--6022},
pmid = {11096097},
title = {{Rvs161p and Rvs167p, the Two Yeast Amphiphysin Homologs, Function Together in Vivo}},
volume = {276},
year = {2001}
}
@misc{Alon2003,
abstract = {This viewpoint comments on recent advances in understanding the design principles of biological networks. It highlights the surprising discovery of "good-engineering" principles in biochemical circuitry that evolved by random tinkering.},
author = {Alon, U.},
booktitle = {Science},
doi = {10.1126/science.1089072},
isbn = {1095-9203 (Electronic)$\backslash$r0036-8075 (Linking)},
issn = {00368075},
pmid = {14512615},
title = {{Biological networks: The tinkerer as an engineer}},
year = {2003}
}
@misc{Engl2009,
abstract = {Systems biology is a new discipline built upon the premise that an understanding of how cells and organisms carry out their functions cannot be gained by looking at cellular components in isolation. Instead, consideration of the interplay between the parts of systems is indispensable for analyzing, modeling, and predicting systems' behavior. Studying biological processes under this premise, systems biology combines experimental techniques and computational methods in order to construct predictive models. Both in building and utilizing models of biological systems, inverse problems arise at several occasions, for example, (i) when experimental time series and steady state data are used to construct biochemical reaction networks, (ii) when model parameters are identified that capture underlying mechanisms or (iii) when desired qualitative behavior such as bistability or limit cycle oscillations is engineered by proper choices of parameter combinations. In this paper we review principles of the modeling process in systems biology and illustrate the ill-posedness and regularization of parameter identification problems in that context. Furthermore, we discuss the methodology of qualitative inverse problems and demonstrate how sparsity enforcing regularization allows the determination of key reaction mechanisms underlying the qualitative behavior.},
author = {Engl, Heinz W. and Flamm, Christoph and K{\"{u}}gler, Philipp and Lu, James and M{\"{u}}ller, Stefan and Schuster, Peter},
booktitle = {Inverse Problems},
doi = {10.1088/0266-5611/25/12/123014},
issn = {13616420},
title = {{Inverse problems in systems biology}},
year = {2009}
}
@article{Saadatpour2013,
abstract = {Given the complexity and interactive nature of biological systems, constructing informative and coherent network models of these systems and subsequently developing efficient approaches to analyze the assembled networks is of immense importance. The integration of network analysis and dynamic modeling enables one to investigate the behavior of the underlying system as a whole and to make experimentally testable predictions about less-understood aspects of the processes involved. In this paper, we present a tutorial on the fundamental steps of Boolean modeling of biological regulatory networks. We demonstrate how to infer a Boolean network model from the available experimental data, analyze the network using graph-theoretical measures, and convert it into a predictive dynamic model. For each step, the pitfalls one may encounter and possible ways to circumvent them are also discussed. We illustrate these steps on a toy network as well as in the context of the Drosophila melanogaster segment polarity gene network. {\textcopyright} 2012 Elsevier Inc.},
author = {Saadatpour, Assieh and Albert, R{\'{e}}ka},
doi = {10.1016/j.ymeth.2012.10.012},
file = {:Users/ozlem/Desktop/1-s2.0-S1046202312002770-main.pdf:pdf},
isbn = {1095-9130 (Electronic) 1046-2023 (Linking)},
issn = {10462023},
journal = {Methods},
keywords = {Biological regulatory networks,Boolean models,Drosophila segment polarity gene network,Dynamic analysis,Structural analysis},
pmid = {23142247},
title = {{Boolean modeling of biological regulatory networks: A methodology tutorial}},
year = {2013}
}
@article{Mussel2010b,
abstract = {Motivation: As the study of information processing in living cells moves from individual pathways to complex regulatory networks, mathematical models and simulation become indispensable tools for analyzing the complex behavior of such networks and can provide deep insights into the functioning of cells. The dynamics of gene expression, for example, can be modeled with Boolean networks (BNs). These are mathematical models of low complexity, but have the advantage of being able to capture essential properties of gene-regulatory networks. However, current implementations of BNs only focus on different sub-aspects of this model and do not allow for a seamless integration into existing preprocessing pipelines. Results: BoolNet efficiently integrates methods for synchronous, asynchronous and probabilistic BNs. This includes reconstructing networks from time series, generating random networks, robustness analysis via perturbation, Markov chain simulations, and identification and visualization of attractors. Availability: The package BoolNet is freely available from the R project at},
archivePrefix = {arXiv},
arxivId = {http://arxiv.org/abs/1604.02208},
author = {M{\"{u}}ssel, Christoph and Hopfensitz, Martin and Kestler, Hans A.},
doi = {10.1093/bioinformatics/btq124},
eprint = {/arxiv.org/abs/1604.02208},
file = {:Users/ozlem/Desktop/Tools/btq124.pdf:pdf},
isbn = {1367-4811 (Linking)},
issn = {13674803},
journal = {Bioinformatics},
number = {10},
pages = {1378--1380},
pmid = {20378558},
primaryClass = {http:},
title = {{BoolNet-an R package for generation, reconstruction and analysis of Boolean networks}},
volume = {26},
year = {2010}
}
@article{Joosten2009,
abstract = {Structural biology, homology modelling and rational drug design require accurate three-dimensional macromolecular coordinates. However, the coordinates in the Protein Data Bank (PDB) have not all been obtained using the latest experimental and computational methods. In this study a method is presented for automated re-refinement of existing structure models in the PDB. A large-scale benchmark with 16 807 PDB entries showed that they can be improved in terms of fit to the deposited experimental X-ray data as well as in terms of geometric quality. The re-refinement protocol uses TLS models to describe concerted atom movement. The resulting structure models are made available through the PDB{\_}REDO databank (http://www.cmbi.ru.nl/pdb{\_}redo/). Grid computing techniques were used to overcome the computational requirements of this endeavour.},
author = {Joosten, Robbie P. and Salzemann, Jean and Bloch, Vincent and Stockinger, Heinz and Berglund, Ann Charlott and Blanchet, Christophe and Bongcam-Rudloff, Erik and Combet, Christophe and {Da Costa}, Ana L. and Deleage, Gilbert and Diarena, Matteo and Fabbretti, Roberto and Fettahi, G{\'{e}}raldine and Flegel, Volker and Gisel, Andreas and Kasam, Vinod and Kervinen, Timo and Korpelainen, Eija and Mattila, Kimmo and Pagni, Marco and Reichstadt, Matthieu and Breton, Vincent and Tickle, Ian J. and Vriend, Gert},
doi = {10.1107/S0021889809008784},
isbn = {0021-8898 (Print)$\backslash$r0021-8898 (Linking)},
issn = {00218898},
journal = {Journal of Applied Crystallography},
keywords = {Grid computing,Protein Data Bank,Refinement,Structure validation,X-ray crystallography},
number = {3},
pages = {376--384},
pmid = {22477769},
title = {{PDB-REDO: Automated re-refinement of X-ray structure models in the PDB}},
volume = {42},
year = {2009}
}
@article{Bardin2017,
abstract = {Risk perceptions concerning genetically modified organisms (GMOs) are often considered to reflect media coverage. However, it might be said that people seek out information consistent with their attitudes and avoid information which could challenge them. This process refers to the selective exposure principle derived from cognitive dissonance theory. Although this principle is now well established, the only two studies carried out to date in the field of GMOs have produced contradictory results. Additionally, no study has considered the link between risk perceptions, threat perceptions and attitudes as possible antecedents of selective exposure in the field of GMOs. The aim of the present research was to fill this gap. Results of a multiple-mediation model showed that people did in fact expose themselves selectively in the field of GMOs: The higher the level of general risk perception they reported, the higher the perceived threat, the more negative their attitude towards GMOs and the greater their inclination to expose themselves to information on the harmful effects of GM food. We discuss the consequences of selective exposure and the potential levers which could favor exposure to pros and cons, thereby also favoring informed food choices.},
author = {Bardin, Brigitte and Perrissol, St{\'{e}}phane and Facca, L{\'{e}}o and Smeding, Annique},
doi = {10.1016/j.foodqual.2016.12.015},
issn = {09503293},
journal = {Food Quality and Preference},
keywords = {Attitude,Genetically modified organisms,Perceived threat,Risk,Selective exposure},
pages = {10--17},
title = {{From risk perception to information selection{\ldots} And not the other way round: Selective exposure mechanisms in the field of genetically modified organisms}},
volume = {58},
year = {2017}
}
@incollection{Hickman1997,
abstract = {X-ray crystallography is one of the major tools available for protein structural analysis. This unit provides an introductory review of the principles of X-ray crystallography that covers how the image is generated and analyzed. The second half of the unit describes strategies for producing crystals of protein, including methods for dealing with proteins that do not easily form crystals.},
author = {Hickman, Alison B. and Davies, David R.},
booktitle = {Current Protocols in Protein Science},
doi = {10.1002/0471140864.ps1703s10},
isbn = {9780471140863},
issn = {1934-3663},
pages = {17.3.1--17.3.15},
pmid = {18429137},
title = {{Principles of Macromolecular X-Ray Crystallography}},
url = {http://doi.wiley.com/10.1002/0471140864.ps1703s10},
year = {1997}
}
@article{Bogdanove2011,
abstract = {Generating and applying new knowledge from the wealth of available genomic information is hindered, in part, by the difficulty of altering nucleotide sequences and expression of genes in living cells in a targeted fashion. Progress has been made in engineering DNA binding domains to direct proteins to particular sequences for mutagenesis or manipulation of transcription; however, achieving the requisite specificities has been challenging. Transcription activator-like (TAL) effectors of plant pathogenic bacteria contain a modular DNA binding domain that appears to overcome this challenge. Comprising tandem, polymorphic amino acid repeats that individually specify contiguous nucleotides in DNA, this domain is being deployed in DNA targeting for applications ranging from understanding gene function in model organisms to improving traits in crop plants to treating genetic disorders in people.},
author = {Bogdanove, A. J. and Voytas, D. F.},
doi = {10.1126/science.1204094},
isbn = {1095-9203 (Electronic)$\backslash$n0036-8075 (Linking)},
issn = {0036-8075},
journal = {Science},
number = {6051},
pages = {1843--1846},
pmid = {21960622},
title = {{TAL Effectors: Customizable Proteins for DNA Targeting}},
url = {http://www.sciencemag.org/cgi/doi/10.1126/science.1204094},
volume = {333},
year = {2011}
}
@misc{Alon2007,
abstract = {Thorough and accessible, this book presents the design principles of biological systems, and highlights the recurring circuit elements that make up biological networks. It provides a simple mathematical framework which can be used to understand and even design biological circuits. The text avoids specialist terms, focusing instead on several well-studied biological systems that concisely demonstrate key principles.An Introduction to Systems Biology: Design Principles of Biological Circuits builds a solid foundation for the intuitive understanding of general principles. It encourages the reader to ask why a system is designed in a particular way and then proceeds to answer with simplified models.},
author = {Alon, Uri},
booktitle = {Chapman HallCRC mathematical and computational biology series},
doi = {citeulike-article-id:1314150},
isbn = {1584886420},
issn = {00368075},
pmid = {14164488},
title = {{An Introduction to Systems Biology: Design Principles of Biological Circuits}},
year = {2007}
}
@article{Hsu2014,
abstract = {Recent advances in genome engineering technologies based on the CRISPR-associated RNA-guided endonuclease Cas9 are enabling the systematic interrogation of mammalian genome function. Analogous to the search function in modern word processors, Cas9 can be guided to specific locations within complex genomes by a short RNA search string. Using this system, DNA sequences within the endogenous genome and their functional outputs are now easily edited or modulated in virtually any organism of choice. Cas9-mediated genetic perturbation is simple and scalable, empowering researchers to elucidate the functional organization of the genome at the systems level and establish causal linkages between genetic variations and biological phenotypes. In this Review, we describe the development and applications of Cas9 for a variety of research or translational applications while highlighting challenges as well as future directions. Derived from a remarkable microbial defense system, Cas9 is driving innovative applications from basic biology to biotechnology and medicine. ?? 2014 Elsevier Inc.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Hsu, Patrick D. and Lander, Eric S. and Zhang, Feng},
doi = {10.1016/j.cell.2014.05.010},
eprint = {NIHMS150003},
isbn = {1097-4172 (Electronic)$\backslash$n0092-8674 (Linking)},
issn = {10974172},
journal = {Cell},
number = {6},
pages = {1262--1278},
pmid = {24906146},
title = {{Development and applications of CRISPR-Cas9 for genome engineering}},
volume = {157},
year = {2014}
}
@misc{Ahmadpour2014,
abstract = {Background The yeast Saccharomyces cerevisiae provides unique opportunities to study roles and regulation of aqua/glyceroporins using frontline tools of genetics and genomics as well as molecular cell and systems biology. Scope of review S. cerevisiae has two similar orthodox aquaporins. Based on phenotypes mediated by gene deletion or overexpression as well as on their expression pattern, the yeast aquaporins play important roles in key aspects of yeast biology: establishment of freeze tolerance, during spore formation as well as determination of cell surface properties for substrate adhesion and colony formation. Exactly how the aquaporins perform those roles and the mechanisms that regulate their function under such conditions remain to be elucidated. S. cerevisiae also has two different aquaglyceroporins. While the role of one of them, Yfl054c, remains to be determined, Fps1 plays critical roles in osmoregulation by controlling the accumulation of the osmolyte glycerol. Fps1 communicates with two osmo-sensing MAPK signalling pathways to perform its functions but the details of Fps1 regulation remain to be determined. Major conclusions Several phenotypes associated with aqua/glyceroporin function in yeasts have been established. However, how water and glycerol transport contribute to the observed effects is not understood in detail. Also many of the basic principles of regulation of yeast aqua/glyceroporins remain to be elucidated. General significance Studying the yeast aquaporins and aquaglyceroporins offers rich insight into the life style, evolution and adaptive responses of yeast and rewards us with discoveries of unexpected roles and regulatory mechanisms of members of this ancient protein family. This article is part of a Special Issue entitled Aquaporins. {\textcopyright} 2013 Elsevier B.V.},
author = {Ahmadpour, Doryaneh and Geijer, Cecilia and Tam{\'{a}}s, Markus J. and Lindkvist-Petersson, Karin and Hohmann, Stefan},
booktitle = {Biochimica et Biophysica Acta - General Subjects},
doi = {10.1016/j.bbagen.2013.09.027},
isbn = {0006-3002 (Print)$\backslash$r0006-3002 (Linking)},
issn = {18728006},
keywords = {Aquaporin,Freeze tolerance,MAPK pathway,Osmoregulation,Signal transduction,Stress resistance},
number = {5},
pages = {1482--1491},
pmid = {24076236},
title = {{Yeast reveals unexpected roles and regulatory features of aquaporins and aquaglyceroporins}},
volume = {1840},
year = {2014}
}
@article{Zhou2017,
abstract = {{\textless}p{\textgreater}Oesophageal squamous cell carcinoma often develop resistance to EGFR tyrosine kinase inhibitors. Here, the authors demonstrate that inhibition of cell cycle regulators CDK4/6 or MAPK blockade enhances the efficacy of EGFR inhibitors for these tumours in mice.{\textless}/p{\textgreater}},
author = {Zhou, Jin and Wu, Zhong and Wong, Gabrielle and Pectasides, Eirini and Nagaraja, Ankur and Stachler, Matthew and Zhang, Haikuo and Chen, Ting and Zhang, Haisheng and Liu, Jie Bin and Xu, Xinsen and Sicinska, Ewa and Sanchez-Vega, Francisco and Rustgi, Anil K. and Diehl, J. Alan and Wong, Kwok Kin and Bass, Adam J.},
doi = {10.1038/ncomms13897},
file = {:Users/ozlem/Downloads/ncomms13897.pdf:pdf},
isbn = {2041-1723 (Electronic)
2041-1723 (Linking)},
issn = {20411723},
journal = {Nature Communications},
pages = {1--12},
pmid = {28059068},
publisher = {Nature Publishing Group},
title = {{CDK4/6 or MAPK blockade enhances efficacy of EGFR inhibition in oesophageal squamous cell carcinoma}},
url = {http://dx.doi.org/10.1038/ncomms13897},
volume = {8},
year = {2017}
}
@article{Hohmann2002a,
abstract = {The ability to adapt to altered availability of free water is a fundamental property of living cells. The principles underlying osmoadaptation are well conserved. The yeast Saccharomyces cerevisiae is an excellent model system with which to study the molecular biology and physiology of osmoadaptation. Upon a shift to high osmolarity, yeast cells rapidly stimulate a mitogen-activated protein (MAP) kinase cascade, the high-osmolarity glycerol (HOG) pathway, which orchestrates part of the transcriptional response. The dynamic operation of the HOG pathway has been well studied, and similar osmosensing pathways exist in other eukaryotes. Protein kinase A, which seems to mediate a response to diverse stress conditions, is also involved in the transcriptional response program. Expression changes after a shift to high osmolarity aim at adjusting metabolism and the production of cellular protectants. Accumulation of the osmolyte glycerol, which is also controlled by altering transmembrane glycerol transport, is of central importance. Upon a shift from high to low osmolarity, yeast cells stimulate a different MAP kinase cascade, the cell integrity pathway. The transcriptional program upon hypo-osmotic shock seems to aim at adjusting cell surface properties. Rapid export of glycerol is an important event in adaptation to low osmolarity. Osmoadaptation, adjustment of cell surface properties, and the control of cell morphogenesis, growth, and proliferation are highly coordinated processes. The Skn7p response regulator may be involved in coordinating these events. An integrated understanding of osmoadaptation requires not only knowledge of the function of many uncharacterized genes but also further insight into the time line of events, their interdependence, their dynamics, and their spatial organization as well as the importance of subtle effects.},
author = {Hohmann, S.},
doi = {10.1128/MMBR.66.2.300-372.2002},
isbn = {1092-2172 (Print)$\backslash$r1092-2172 (Linking)},
issn = {1092-2172},
journal = {Microbiology and Molecular Biology Reviews},
number = {2},
pages = {300--372},
pmid = {12040128},
title = {{Osmotic Stress Signaling and Osmoadaptation in Yeasts}},
url = {http://mmbr.asm.org/cgi/doi/10.1128/MMBR.66.2.300-372.2002},
volume = {66},
year = {2002}
}
@article{Stacey1987,
abstract = {Microinjection of p21ras induced c-fos protein accumulation in three types of 3T3 cells. The induction was rapid and efficient and persisted for many hours. In addition, anti-ras antibody dramatically reduced c-fos accumulation after serum stimulation of injected cells. However, cells which expressed p21ras continuously did not maintain a high level of c-fos expression.},
author = {Stacey, D W and Watson, T and Kung, H F and Curran, T},
doi = {10.1128/MCB.7.1.523},
journal = {Molecular and Cellular Biology},
month = {jan},
number = {1},
pages = {523 LP  -- 527},
title = {{Microinjection of transforming ras protein induces c-fos expression.}},
url = {http://mcb.asm.org/content/7/1/523.abstract},
volume = {7},
year = {1987}
}
@article{Klamt2006,
abstract = {BACKGROUND: Structural analysis of cellular interaction networks contributes to a deeper understanding of network-wide interdependencies, causal relationships, and basic functional capabilities. While the structural analysis of metabolic networks is a well-established field, similar methodologies have been scarcely developed and applied to signaling and regulatory networks. RESULTS: We propose formalisms and methods, relying on adapted and partially newly introduced approaches, which facilitate a structural analysis of signaling and regulatory networks with focus on functional aspects. We use two different formalisms to represent and analyze interaction networks: interaction graphs and (logical) interaction hypergraphs. We show that, in interaction graphs, the determination of feedback cycles and of all the signaling paths between any pair of species is equivalent to the computation of elementary modes known from metabolic networks. Knowledge on the set of signaling paths and feedback loops facilitates the computation of intervention strategies and the classification of compounds into activators, inhibitors, ambivalent factors, and non-affecting factors with respect to a certain species. In some cases, qualitative effects induced by perturbations can be unambiguously predicted from the network scheme. Interaction graphs however, are not able to capture AND relationships which do frequently occur in interaction networks. The consequent logical concatenation of all the arcs pointing into a species leads to Boolean networks. For a Boolean representation of cellular interaction networks we propose a formalism based on logical (or signed) interaction hypergraphs, which facilitates in particular a logical steady state analysis (LSSA). LSSA enables studies on the logical processing of signals and the identification of optimal intervention points (targets) in cellular networks. LSSA also reveals network regions whose parametrization and initial states are crucial for the dynamic behavior. We have implemented these methods in our software tool CellNetAnalyzer (successor of FluxAnalyzer) and illustrate their applicability using a logical model of T-Cell receptor signaling providing non-intuitive results regarding feedback loops, essential elements, and (logical) signal processing upon different stimuli. CONCLUSION: The methods and formalisms we propose herein are another step towards the comprehensive functional analysis of cellular interaction networks. Their potential, shown on a realistic T-cell signaling model, makes them a promising tool.},
author = {Klamt, Steffen and Saez-Rodriguez, Julio and Lindquist, Jonathan A. and Simeoni, Luca and Gilles, Ernst D.},
doi = {10.1186/1471-2105-7-56},
isbn = {1471-2105 (Electronic)$\backslash$n1471-2105 (Linking)},
issn = {14712105},
journal = {BMC Bioinformatics},
pmid = {16464248},
title = {{A methodology for the structural and functional analysis of signaling and regulatory networks}},
year = {2006}
}
@article{Rodrigues2000,
abstract = {The Gab1 protein is tyrosine phosphorylated in response to various growth factors and serves as a docking protein that recruits a number of downstream signaling proteins, including phosphatidylinositol 3-kinase (PI-3 kinase). To determine the role of Gab1 in signaling via the epidermal growth factor (EGF) receptor (EGFR) we tested the ability of Gab1 to associate with and modulate signaling by this receptor. We show that Gab1 associates with the EGFR in vivo and in vitro via pTyr sites 1068 and 1086 in the carboxy-terminal tail of the receptor and that overexpression of Gab1 potentiates EGF-induced activation of the mitogen-activated protein kinase and Jun kinase signaling pathways. A mutant of Gab1 unable to bind the p85 subunit of PI-3 kinase is defective in potentiating EGFR signaling, confirming a role for PI-3 kinase as a downstream effector of Gab1. Inhibition of PI-3 kinase by a dominant-interfering mutant of p85 or by Wortmannin treatment similarly impairs Gab1-induced enhancement of signaling via the EGFR. The PH domain of Gab1 was shown to bind specifically to phosphatidylinositol 3,4,5-triphosphate [PtdIns(3,4,5)P3], a product of PI-3 kinase, and is required for activation of Gab1-mediated enhancement of EGFR signaling. Moreover, the PH domain mediates Gab1 translocation to the plasma membrane in response to EGF and is required for efficient tyrosine phosphorylation of Gab1 upon EGF stimulation. In addition, overexpression of Gab1 PH domain blocks Gab1 potentiation of EGFR signaling. Finally, expression of the gene for the lipid phosphatase PTEN, which dephosphorylates PtdIns(3,4, 5)P3, inhibits EGF signaling and translocation of Gab1 to the plasma membrane. These results reveal a novel positive feedback loop, modulated by PTEN, in which PI-3 kinase functions as both an upstream regulator and a downstream effector of Gab1 in signaling via the EGFR.},
author = {Rodrigues, G. A. and Falasca, M. and Zhang, Z. and Ong, S. H. and Schlessinger, J.},
doi = {10.1128/MCB.20.4.1448-1459.2000},
isbn = {0270-7306 (Print)},
issn = {0270-7306},
journal = {Molecular and Cellular Biology},
pmid = {10648629},
title = {{A Novel Positive Feedback Loop Mediated by the Docking Protein Gab1 and Phosphatidylinositol 3-Kinase in Epidermal Growth Factor Receptor Signaling}},
year = {2000}
}
@article{Albert2014,
abstract = {The biomolecules inside or near cells form a complex interacting system. Cellular phenotypes and behaviors arise from the totality of interactions among the components of this system. A fruitful way of modeling interacting biomolecular systems is by network-based dynamic models that characterize each component by a state variable, and describe the change in the state variables due to the interactions in the system. Dynamic models can capture the stable state patterns of this interacting system and can connect them to different cell fates or behaviors. A Boolean or logic model characterizes each biomolecule by a binary state variable that relates the abundance of that molecule to a threshold abundance necessary for downstream processes. The regulation of this state variable is described in a parameter free manner, making Boolean modeling a practical choice for systems whose kinetic parameters have not been determined. Boolean models integrate the body of knowledge regarding the components and interactions of biomolecular systems, and capture the system's dynamic repertoire, for example the existence of multiple cell fates. These models were used for a variety of systems and led to important insights and predictions. Boolean models serve as an efficient exploratory model, a guide for follow-up experiments, and as a foundation for more quantitative models.},
author = {Albert, R{\'{e}}ka and Thakar, Juilee},
doi = {10.1002/wsbm.1273},
isbn = {1111111111},
issn = {1939005X},
journal = {Wiley Interdisciplinary Reviews: Systems Biology and Medicine},
pmid = {25269159},
title = {{Boolean modeling: A logic-based dynamic approach for understanding signaling and regulatory networks and for making useful predictions}},
year = {2014}
}
@article{Hou2007,
abstract = {Ribosomal S6 kinase 1 (S6K1), as a key regulator of mRNA translation, plays an important role in cell cycle progression through the G(1) phase of proliferating cells and in the synaptic plasticity of terminally differentiated neurons. Activation of S6K1 involves the phosphorylation of its multiple Ser/Thr residues, including the proline-directed sites (Ser-411, Ser-418, Thr-421, and Ser-424) in the autoinhibitory domain near the C terminus. Phosphorylation at Thr-389 is also a crucial event in S6K1 activation. Here, we report that S6K1 phosphorylation at Ser-411 is required for the rapamycin-sensitive phosphorylation of Thr-389 and the subsequent activation of S6K1. Mutation of Ser-411 to Ala ablated insulin-induced Thr-389 phosphorylation and S6K1 activation, whereas mutation mimicking Ser-411 phosphorylation did not show any effect. Furthermore, phosphomimetic mutation of Thr-389 overcame the inhibitory effect of the mutation S411A. Thus, Ser-411 phosphorylation regulates S6K1 activation via the control of Thr-389 phosphorylation. In nervous system neurons, Cdk5-p35 kinase associates with S6K1 via the direct interaction between p35 and S6K1 and catalyzes S6K1 phosphorylation specifically at Ser-411. Inhibition of the Cdk5 activity or suppression of Cdk5 expression blocked S6K1 phosphorylation at Ser-411 and Thr-389, resulting in S6K1 inactivation. Similar results were obtained by treating asynchronous populations of proliferating cells with the CDK inhibitor compound roscovitine. Altogether, our findings suggest a novel mechanism by which the CDK-mediated phosphorylation regulates the activation of S6K1.},
author = {Hou, Zhibo and He, Lisheng and Qi, Robert Z.},
doi = {10.1074/jbc.M607836200},
isbn = {0021-9258 (Print)$\backslash$r0021-9258 (Linking)},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {17220300},
title = {{Regulation of S6 kinase 1 activation by phosphorylation at Ser-411}},
year = {2007}
}
@article{Teorey1986,
abstract = {A database design methodology is defined for the design of large relational databases. First, the data requirements are conceptualized using an extended entity-relationship model, with the extensions being additional semantics such as ternary relationships, optional relationships, and the generalization abstraction. The extended entity-relationship model is then decomposed according to a set of basic entity-relationship constructs, and these are transformed into candidate relations. A set of basic transformations has been developed for the three types of relations: entity relations, extended entity relations, and relationship relations. Candidate relations are further analyzed and modified to attain the highest degree of normalization desired. The methodology produces database designs that are not only accurate representations of reality, but flexible enough to accommodate future processing requirements. It also reduces the number of data dependencies that must be analyzed, using the extended ER model conceptualization, and maintains data integrity through normalization. This approach can be implemented manually or in a simple software package as long as a "good" solution is acceptable and absolute optimality is not required.},
archivePrefix = {arXiv},
arxivId = {arXiv:1011.1669v3},
author = {Teorey, Toby J. and Yang, Dongqing and Fry, James P.},
doi = {10.1145/7474.7475},
eprint = {arXiv:1011.1669v3},
isbn = {9788578110796},
issn = {03600300},
journal = {ACM Computing Surveys},
pmid = {25246403},
title = {{A logical design methodology for relational databases using the extended entity-relationship model}},
year = {1986}
}
@article{Sekioka2008,
abstract = {We report an electrochemical ??-aminobutyric acid (GABA) sensor with an improved detection limit based on stable ??-nicotinamide adenine dinucleotide phosphate (NADPH) oxidation with an extremely low background current using an electron cyclotron resonance (ECR)-sputtered carbon film electrode. The sensor comprised an ECR carbon electrode modified with gabase co-immobilized bovine serum albumin. We obtained stable responses for NADPH without any electrode surface fouling by electrochemically pretreating the ECR carbon electrode because ECR carbon has an extremely flat surface even after pretreatment and increasing the surface oxygen made the surface more hydrophilic thus suppressing oxidized NADPH (NADP+) fouling of the surface. As a result, we obtained a very low detection limit of 10 nM for NADPH, which was more than one order of magnitude better than that of a conventional glassy carbon electrode (250 nM). We also achieved a low detection limit of 30 nM GABA within 2 min by modifying the pretreated ECR carbon electrode with gabase. The proposed electrochemical GABA sensor exhibited a lower detection limit than any previously reported GABA sensor. ?? 2007 Elsevier B.V. All rights reserved.},
author = {Sekioka, Naoyuki and Kato, Dai and Kurita, Ryoji and Hirono, Shigeru and Niwa, Osamu},
doi = {10.1016/j.snb.2007.08.040},
issn = {09254005},
journal = {Sensors and Actuators, B: Chemical},
keywords = {ECR-sputtered carbon film,Electrochemical pretreatment,Electron cyclotron resonance (ECR),GABA,NADPH},
number = {1},
pages = {442--449},
title = {{Improved detection limit for an electrochemical ??-aminobutyric acid sensor based on stable NADPH detection using an electron cyclotron resonance sputtered carbon film electrode}},
volume = {129},
year = {2008}
}
@article{Brtva1995,
abstract = {A key event for Ras transformation involves the direct physical association between Ras and the Raf-1 kinase. This interaction promotes both Raf translocation to the plasma membrane and activation of Raf kinase activity. Although substantial experimental evidence has demonstrated that Raf residues 51-131 alone are sufficient for Ras binding, conflicting observations have suggested that the Raf cysteine-rich domain (residues 139-184) may also be important for interaction with Ras. To clarify the role of the Raf cysteine-rich domain in Ras-Raf binding, we have compared the ability of two distinct Raf fragments to interact with Ras using both in vitro Ras binding and in vivo Ras inhibition assays. First, we determined that both Raf sequences 2-140 and 139-186 (designated Raf-Cys) showed preferential binding to active, GTP-bound Ras in vitro. Second, we observed that Raf-Cys antagonized oncogenic Ras(Q61L)-mediated transactivation of Ras-responsive elements and focus-forming activity in NIH 3T3 cells and insulin-induced germinal vesicle breakdown in Xenopus laevis oocytes in vivo. This inhibitory activity suggests that Raf-Cys can interact with Ras in vivo. Taken together, these results suggest that Ras interaction with two distinct domains of Raf-1 may be important in Ras-mediated activation of Raf kinase activity.},
archivePrefix = {arXiv},
arxivId = {1403.2970},
author = {Brtva, T. R. and Drugan, J. K. and Ghosh, S. and Terrell, R. S. and Campbell-Burk, S. and Bell, R. M. and Der, C. J.},
doi = {10.1074/jbc.270.17.9809},
eprint = {1403.2970},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {7730360},
title = {{Two distinct Raf domains mediate interaction with Ras}},
year = {1995}
}
@article{Lahdesmaki2003,
author = {L{\"{a}}hdesm{\"{a}}ki, H and Shmulevich, I and Yli-Harja, O},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/L{\"{a}}hdesm{\"{a}}ki, Shmulevich, Yli-Harja - 2003 - On Learning Gene Regulatory Networks Under the Boolean Network Model.pdf:pdf},
issn = {0885-6125},
journal = {Machine Learning},
number = {1-2},
pages = {147--167},
title = {{On Learning Gene Regulatory Networks Under the Boolean Network Model}},
volume = {52},
year = {2003}
}
@article{Handorf2012a,
abstract = {MOTIVATION: The understanding of the molecular sources for diseases like cancer can be significantly improved by computational models. Recently, Boolean networks have become very popular for modeling signaling and regulatory networks. However, such models rely on a set of Boolean functions that are in general not known. Unfortunately, while detailed information on the molecular interactions becomes available in large scale through electronic databases, the information on the Boolean functions does not become available simultaneously and has to be included manually into the models, if at all known.$\backslash$n$\backslash$nRESULTS: We propose a new Boolean approach which can directly utilize the mechanistic network information available through modern databases. The Boolean function is implicitly defined by the reaction mechanisms. Special care has been taken for the treatment of kinetic features like inhibition. The method has been applied to a signaling model combining the Wnt and MAPK pathway.$\backslash$n$\backslash$nAVAILABILITY: A sample C++ implementation of the proposed method is available for Linux and compatible systems through http://code.google.com/p/libscopes/wiki/Paper2011.},
author = {Handorf, T. and Klipp, E.},
doi = {10.1093/bioinformatics/btr697},
isbn = {1367-4811 (Electronic)$\backslash$n1367-4803 (Linking)},
issn = {13674803},
journal = {Bioinformatics},
pmid = {22199382},
title = {{Modeling mechanistic biological networks: An advanced Boolean approach}},
year = {2012}
}
@article{Cokelaer2014a,
author = {Cokelaer, Thomas and Saez-rodriguez, Julio},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Cokelaer, Saez-rodriguez - 2014 - CellNOpt a brief overview.pdf:pdf},
number = {April},
title = {{CellNOpt : a brief overview}},
year = {2014}
}
@article{Jones2001,
author = {Jones, Steven M and Kazlauskas, Andrius},
journal = {Nature Cell Biology},
month = {jan},
pages = {165},
publisher = {Nature Publishing Group},
title = {{Growth-factor-dependent mitogenesis requires two distinct phases of signalling}},
url = {https://doi.org/10.1038/35055073 http://10.0.4.14/35055073 https://www.nature.com/articles/ncb0201{\_}165{\#}supplementary-information},
volume = {3},
year = {2001}
}
@article{Risso2011,
abstract = {Transcriptome sequencing (RNA-Seq) has become the assay of choice for high-throughput studies of gene expression. However, as is the case with microarrays, major technology-related artifacts and biases affect the resulting expression measures. Normalization is therefore essential to ensure accurate inference of expression levels and subsequent analyses thereof. We focus on biases related to GC-content and demonstrate the existence of strong sample-specific GC-content effects on RNA-Seq read counts, which can substantially bias differential expression analysis. We propose three simple within-lane gene-level GC-content normalization approaches and assess their performance on two different RNA-Seq datasets, involving different species and experimental designs. Our methods are compared to state-of-the-art normalization procedures in terms of bias and mean squared error for expression fold-change estimation and in terms of Type I error and p-value distributions for tests of differential expression. The exploratory data analysis and normalization methods proposed in this article are implemented in the open-source Bioconductor R package EDASeq. Our within-lane normalization procedures, followed by between-lane normalization, reduce GC-content bias and lead to more accurate estimates of expression fold-changes and tests of differential expression. Such results are crucial for the biological interpretation of RNA-Seq experiments, where downstream analyses can be sensitive to the supplied lists of genes.},
author = {Risso, Davide and Schwartz, Katja and Sherlock, Gavin and Dudoit, Sandrine},
doi = {10.1186/1471-2105-12-480},
isbn = {1471-2105 (Electronic)$\backslash$r1471-2105 (Linking)},
issn = {1471-2105},
journal = {BMC Bioinformatics},
number = {1},
pages = {480},
pmid = {22177264},
title = {{GC-Content Normalization for RNA-Seq Data}},
url = {http://bmcbioinformatics.biomedcentral.com/articles/10.1186/1471-2105-12-480},
volume = {12},
year = {2011}
}
@article{Kala2014,
abstract = {The genome packaging reactions of tailed bacteriophages and herpes viruses require the activity of a terminase enzyme, which is comprised of large and small subunits. Phage genomes are replicated as linear concatemers composed of multiple copies of the genome joined end to end. As the terminase enzyme packages the genome into the phage capsid, it cleaves the DNA into single genome-length units. In this work, we show that the phage HK97 HNH protein, gp74, is required for the specific endonuclease activity of HK97 terminase and is essential for phage head morphogenesis. HNH proteins are a very common family of proteins generally associated with nuclease activity that are found in all kingdoms of life. We show that the activity of gp74 in terminase-mediated cleavage of the phage cos site relies on the presence of an HNH motif active-site residue, and that the large subunit of HK97 terminase physically interacts with gp74. Bioinformatic analysis reveals that the role of HNH proteins in terminase function is widespread among long-tailed phages and is uniquely required for the activity of the Terminase{\_}1 family of large terminase proteins.},
author = {Kala, S. and Cumby, N. and Sadowski, P. D. and Hyder, B. Z. and Kanelis, V. and Davidson, A. R. and Maxwell, K. L.},
doi = {10.1073/pnas.1320952111},
isbn = {0027-8424},
issn = {0027-8424},
journal = {Proceedings of the National Academy of Sciences},
number = {16},
pages = {6022--6027},
pmid = {24711378},
title = {{HNH proteins are a widespread component of phage DNA packaging machines}},
url = {http://www.pnas.org/cgi/doi/10.1073/pnas.1320952111},
volume = {111},
year = {2014}
}
@article{Buchel2012,
abstract = {MOTIVATION: The biological pathway exchange language (BioPAX) and the systems biology markup language (SBML) belong to the most popular modeling and data exchange languages in systems biology. The focus of SBML is quantitative modeling and dynamic simulation of models, whereas the BioPAX specification concentrates mainly on visualization and qualitative analysis of pathway maps. BioPAX describes reactions and relations. In contrast, SBML core exclusively describes quantitative processes such as reactions. With the SBML qualitative models extension (qual), it has recently also become possible to describe relations in SBML. Before the development of SBML qual, relations could not be properly translated into SBML. Until now, there exists no BioPAX to SBML converter that is fully capable of translating both reactions and relations.$\backslash$n$\backslash$nRESULTS: The entire nature pathway interaction database has been converted from BioPAX (Level 2 and Level 3) into SBML (Level 3 Version 1) including both reactions and relations by using the new qual extension package. Additionally, we present the new webtool BioPAX2SBML for further BioPAX to SBML conversions. Compared with previous conversion tools, BioPAX2SBML is more comprehensive, more robust and more exact.$\backslash$n$\backslash$nAVAILABILITY: BioPAX2SBML is freely available at http://webservices.cs.uni-tuebingen.de/ and the complete collection of the PID models is available at http://www.cogsys.cs.uni-tuebingen.de/downloads/Qualitative-Models/.},
author = {B{\"{u}}chel, Finja and Wrzodek, Clemens and Mittag, Florian and Dr{\"{a}}ger, Andreas and Eichner, Johannes and Rodriguez, Nicolas and {Le Nov{\`{e}}re}, Nicolas and Zell, Andreas},
doi = {10.1093/bioinformatics/bts508},
file = {:Users/ozlem/Dropbox/papers/Translation of Relations/bts508.pdf:pdf},
isbn = {1367-4811 (Electronic)$\backslash$r1367-4803 (Linking)},
issn = {13674803},
journal = {Bioinformatics},
number = {20},
pages = {2648--2653},
pmid = {22923304},
title = {{Qualitative translation of relations from BioPAX to SBML qual}},
volume = {28},
year = {2012}
}
@misc{Alleva2012,
abstract = {Osmolarity not only plays a key role in celluar homeostasis but also challenges cell survival. The molecular understanding of osmosis has not yet been completely achieved, and the discovery of aquaporins as molecular entities involved in water transport has caused osmosis to again become a focus of research. The main questions that need to be answered are the mechanism underlying the osmotic permeability coefficients and the extent to which aquaporins change our understanding of osmosis. Here, attempts to answer these questions are discussed. Critical aspects of the state of the state of knowledge on osmosis, a topic that has been studied since 19th century, are reviewed and integrated with the available information provided by in vivo, in vitro and in silico approaches. {\textcopyright} 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.},
author = {Alleva, Karina and Chara, Osvaldo and Amodeo, Gabriela},
booktitle = {FEBS Letters},
doi = {10.1016/j.febslet.2012.06.013},
isbn = {0014-5793},
issn = {00145793},
keywords = {Aquaporin,Osmosis,Osmotic permeability,Phenomenological law,Water transport},
number = {19},
pages = {2991--2999},
pmid = {22728434},
title = {{Aquaporins: Another piece in the osmotic puzzle}},
volume = {586},
year = {2012}
}
@misc{Wang2012a,
abstract = {Mathematical modeling of biological processes provides deep insights into complex cellular systems. While quantitative and continuous models such as differential equations have been widely used, their use is obstructed in systems wherein the knowledge of mechanistic details and kinetic parameters is scarce. On the other hand, a wealth of molecular level qualitative data on individual components and interactions can be obtained from the experimental literature and high-throughput technologies, making qualitative approaches such as Boolean network modeling extremely useful. In this paper, we build on our research to provide a methodology overview of Boolean modeling in systems biology, including Boolean dynamic modeling of cellular networks, attractor analysis of Boolean dynamic models, as well as inferring biological regulatory mechanisms from high-throughput data using Boolean models. We finally demonstrate how Boolean models can be applied to perform the structural analysis of cellular networks. This overview aims to acquaint life science researchers with the basic steps of Boolean modeling and its applications in several areas of systems biology.},
author = {Wang, Rui Sheng and Saadatpour, Assieh and Albert, R{\'{e}}ka},
booktitle = {Physical Biology},
doi = {10.1088/1478-3975/9/5/055001},
isbn = {1478-3967},
issn = {14783967},
pmid = {23011283},
title = {{Boolean modeling in systems biology: An overview of methodology and applications}},
year = {2012}
}
@article{Basyn2003,
abstract = {Few structures of membrane proteins are known and their relationships with the membrane are unclear. In a previous report, 20 X-ray structures of transmembrane proteins were analyzed in silico for their orientation in a 36A-thick membrane [J. Mol. Graph. Model. 20 (2001) 235]. In this paper, we use the same approach to analyze how the insertion of the X-ray structures varies with the bilayer thickness. The protein structures are kept constant and, at each membrane thickness, the protein is allowed to tilt and rotate in order to accommodate at their best. The conditions are said to be optimal when the energy of insertion is minimal. The results show that most helix bundles require thicker membranes than porin barrels. Moreover, in a few instances, the ideal membrane thickness is unrealistic with respect to natural membranes supporting that the X-ray structure requires adaptation to stabilize in membrane. For instance, the squalene cyclase could adapt by bending the side chains of its ring of lysine and arginine in order to increase the hydrophobic surface in contact with membranes. We analyzed the distribution of amino acids in the water, interface and acyl chain layers of the membrane and compared with the literature.},
author = {Basyn, Frederic and Spies, Benoit and Bouffioux, Olivier and Thomas, Annick and Brasseur, Robert},
doi = {10.1016/S1093-3263(03)00122-0},
issn = {1093-3263},
journal = {Journal of molecular graphics {\&} modelling},
keywords = {Carrier Proteins,Carrier Proteins: chemistry,Computational Biology,Crystallography,Lipid Bilayers,Lipid Bilayers: chemistry,Membrane Proteins,Membrane Proteins: chemistry,Models,Molecular,X-Ray},
number = {1},
pages = {11--21},
pmid = {12798387},
title = {{Insertion of X-ray structures of proteins in membranes.}},
url = {http://www.sciencedirect.com/science/article/pii/S1093326303001220},
volume = {22},
year = {2003}
}
@article{Goodsell1996,
abstract = {AutoDock is a suite of C programs used to predict the bound conformations of a small, flexible ligand to a macromolecular target of known structure. The technique combines simulated annealing for conformation searching with a rapid grid-based method of energy evaluation. This paper reviews recent applications of the technique and describes the enhancements included in the current release.},
author = {Goodsell, D S and Morris, G M and Olson, A J},
doi = {10.1002/(SICI)1099-1352(199601)9:1<1::AID-JMR241>3.0.CO;2-6 [pii]\r10.1002/(SICI)1099-1352(199601)9:1&lt;1::AID-JMR241&gt;3.0.CO;2-6},
isbn = {0952-3499 (Print)$\backslash$r0952-3499 (Linking)},
issn = {0952-3499},
journal = {J Mol Recognit},
keywords = {*Computer Simulation,*Ligands,*Molecular Conformation,*Software,Carrier Proteins/chemistry,Enzymes/metabolism,HIV Protease Inhibitors/chemistry/pharmacology,Immunoglobulin Fab Fragments/metabolism,Models, Molecular,Protein Binding,Receptors, Amino Acid/metabolism},
number = {1},
pages = {1--5},
pmid = {8723313},
title = {{Automated docking of flexible ligands: applications of AutoDock}},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve{\&}db=PubMed{\&}dopt=Citation{\&}list{\_}uids=8723313},
volume = {9},
year = {1996}
}
@article{Kuscu2014a,
abstract = {RNA-guided genome editing with the CRISPR-Cas9 system has great potential for basic and clinical research, but the determinants of targeting specificity and the extent of off-target cleavage remain insufficiently understood. Using chromatin immunoprecipitation and high-throughput sequencing (ChIP-seq), we mapped genome-wide binding sites of catalytically inactive Cas9 (dCas9) in HEK293T cells, in combination with 12 different single guide RNAs (sgRNAs). The number of off-target sites bound by dCas9 varied from approximately 10 to {\textgreater}1,000 depending on the sgRNA. Analysis of off-target binding sites showed the importance of the PAM-proximal region of the sgRNA guiding sequence and that dCas9 binding sites are enriched in open chromatin regions. When targeted with catalytically active Cas9, some off-target binding sites had indels above background levels in a region around the ChIP-seq peak, but generally at lower rates than the on-target sites. Our results elucidate major determinants of Cas9 targeting, and we show that ChIP-seq allows unbiased detection of Cas9 binding sites genome-wide.},
author = {Kuscu, Cem and Arslan, Sevki and Singh, Ritambhara and Thorpe, Jeremy and Adli, Mazhar},
doi = {10.1038/nbt.2916},
isbn = {1546-1696 (Electronic)$\backslash$r1087-0156 (Linking)},
issn = {1087-0156},
journal = {Nature Biotechnology},
number = {7},
pages = {677--683},
pmid = {24837660},
title = {{Genome-wide analysis reveals characteristics of off-target sites bound by the Cas9 endonuclease}},
url = {http://www.nature.com/doifinder/10.1038/nbt.2916},
volume = {32},
year = {2014}
}
@article{Gawron2016,
abstract = {Our growing knowledge about various molecular mechanisms is becoming increasingly more structured and accessible. Different repositories of molecular interactions and available literature enable construction of focused and high-quality molecular interaction networks. Novel tools for curation and exploration of such networks are needed, in order to foster the development of a systems biology environment. In particular, solutions for visualization, annotation and data cross-linking will facilitate usage of network-encoded knowledge in biomedical research. To this end we developed the MINERVA (Molecular Interaction NEtwoRks VisuAlization) platform, a standalone webservice supporting curation, annotation and visualization of molecular interaction networks in Systems Biology Graphical Notation (SBGN)-compliant format. MINERVA provides automated content annotation and verification for improved quality control. The end users can explore and interact with hosted networks, and provide direct feedback to content curators. MINERVA enables mapping drug targets or overlaying experimental data on the visualized networks. Extensive export functions enable downloading areas of the visualized networks as SBGN-compliant models for efficient reuse of hosted networks. The software is available under Affero GPL 3.0 as a Virtual Machine snapshot, Debian package and Docker instance at http://r3lab. uni.lu/web/minerva-website/. We believe that MINERVA is an important contribution to systems biology community, as its architecture enables set-up of locally or globally accessible SBGN-oriented repositories of molecular interaction networks. Its functionalities allow overlay of multiple information layers, facilitating exploration of content and interpretation of data. Moreover, annotation and verification workflows of MINERVA improve the efficiency of curation of networks, allowing life-science researchers to better engage in development and use of biomedical knowledge repositories.},
author = {Gawron, Piotr and Ostaszewski, Marek and Satagopam, Venkata and Gebel, Stephan and Mazein, Alexander and Kuzma, Michal and Zorzan, Simone and McGee, Fintan and Otjacques, Beno{\^{i}}t and Balling, Rudi and Schneider, Reinhard},
doi = {10.1038/npjsba.2016.20},
file = {:Users/ozlem/Desktop/papers/Gawron2016.pdf:pdf},
issn = {2056-7189},
journal = {npj Systems Biology and Applications},
number = {1},
pages = {16020},
pmid = {28725475},
publisher = {The Author(s)},
title = {{MINERVA—a platform for visualization and curation of molecular interaction networks}},
url = {http://www.nature.com/articles/npjsba201620},
volume = {2},
year = {2016}
}
@article{Tong2005a,
abstract = {Synthetic lethality occurs when the combination of two mutations leads to an inviable organism. Screens for synthetic lethal genetic interactions have been used extensively to identify genes whose products buffer one another or impinge on the same essential pathway. For the yeast Saccharomyces cerevisiae, we developed a method termed Synthetic Genetic Array (SGA) analysis, which offers an efficient approach for the systematic construction of double mutants and enables a global analysis of synthetic lethal genetic interactions. In a typical SGA screen, a query mutation is crossed to an ordered array of approx 5000 viable gene deletion mutants (representing approximately 80{\%} of all yeast genes) such that meiotic progeny harboring both mutations can be scored for fitness defects. This array-based approach automates yeast genetic analysis in general and can be easily adapted for a number of different screens, including genetic suppression, plasmid shuffling, dosage lethality, or suppression.},
author = {Tong, a H and Boone, C},
doi = {10.1016/S0076-6879(10)70007-0},
isbn = {1064-3745 (Print)$\backslash$n1064-3745 (Linking)},
issn = {1064-3745},
journal = {Methods in molecular biology (Clifton, NJ)},
keywords = {Alleles,Base Sequence,DNA Primers,Gene Deletion,Genes: Fungal,Genes: Lethal,Genetic Techniques,Mutation,Mycology,Oligonucleotide Array Sequence Analysis,Plasmids,Polymerase Chain Reaction,Saccharomyces cerevisiae,Spores: Fungal},
number = {1},
pages = {171--192},
pmid = {16118434},
title = {{Synthetic genetic array analysis in Saccharomyces cerevisiae}},
url = {http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed{\&}Cmd=Retrieve{\&}list{\_}uids=16118434{\&}dopt=abstractplus{\%}5Cnpapers://858f277f-6672-4397-a499-b541eeb06ad9/Paper/p1368},
volume = {313},
year = {2005}
}
@article{Zerbino2015,
abstract = {Most genomic variants associated with phenotypic traits or disease do not fall within gene coding regions, but in regulatory regions, rendering their interpretation difficult. We collected public data on epigenetic marks and transcription factor binding in human cell types and used it to construct an intuitive summary of regulatory regions in the human genome. We verified it against independent assays for sensitivity. The Ensembl Regulatory Build will be progressively enriched when more data is made available. It is freely available on the Ensembl browser, from the Ensembl Regulation MySQL database server and in a dedicated track hub.},
archivePrefix = {arXiv},
arxivId = {cs/9605103},
author = {Zerbino, Daniel R. and Wilder, Steven P. and Johnson, Nathan and Juettemann, Thomas and Flicek, Paul R.},
doi = {10.1186/s13059-015-0621-5},
eprint = {9605103},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Zerbino et al. - 2015 - The Ensembl Regulatory Build.pdf:pdf},
isbn = {10.1186/s13059-015-0621-5},
issn = {1474760X},
journal = {Genome Biology},
number = {1},
pages = {1--8},
pmid = {25887522},
primaryClass = {cs},
publisher = {???},
title = {{The Ensembl Regulatory Build}},
url = {???},
volume = {16},
year = {2015}
}
@misc{Salmena2008,
abstract = {Since its discovery as the elusive tumor suppressor gene at the frequently mutated 10q23 locus, PTEN has been identified as lost or mutated in several sporadic and heritable tumor types. A decade of work has established that PTEN is a nonredundant phosphatase that is essential for regulating the highly oncogenic prosurvival PI3K/AKT signaling pathway. This review discusses emerging modes of PTEN function and regulation, and speculates about how manipulation of PTEN function could be used for cancer therapy. {\textcopyright} 2008 Elsevier Inc. All rights reserved.},
author = {Salmena, Leonardo and Carracedo, Arkaitz and Pandolfi, Pier Paolo},
booktitle = {Cell},
doi = {10.1016/j.cell.2008.04.013},
isbn = {0092-8674},
issn = {00928674},
pmid = {18455982},
title = {{Tenets of PTEN Tumor Suppression}},
year = {2008}
}
@article{Ideker2001,
abstract = {Systems biology studies biological systems by systematically perturbing them (biologically, genetically, or chemically); monitoring the gene, protein, and informational pathway responses; integrating these data; and ultimately, formulating mathematical models that describe the structure of the system and its response to individual perturbations. The emergence of systems biology is described, as are several examples of specific systems approaches},
author = {Ideker, Trey and Galitski, Timothy and Hood, Leroy},
doi = {10.1146/annurev.genom.2.1.343},
isbn = {1527-8204 (Print)$\backslash$r1527-8204 (Linking)},
issn = {1527-8204},
journal = {Annu. Rev. Genomics Hum. Genet.},
keywords = {and,and ultimately,biological information,biologically,discovery sciences,formulating,genetically,genome,informational pathway responses,ing them,integrating these data,monitoring the gene,or chemically,protein,proteome,s abstract systems biology,studies biological systems by,systematically perturb-},
pmid = {11701654},
title = {{A NEW APPROACH TO DECODING LIFE: Systems Biology}},
year = {2001}
}
@article{Wolff2003,
abstract = {The coordinated polarization of cells within an epithelium is required for the development and function of some tissues. Recent work has shown that the EGF receptor signaling pathway plays a key role in establishing epithelial polarity in the compound eye of Drosophila.},
author = {Wolff, Tanya},
doi = {10.1016/j.cub.2003.09.053},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Wolff - 2003 - EGF Receptor Signaling Putting a New Spin on Eye Development.pdf:pdf},
issn = {09609822},
journal = {Current Biology},
number = {20},
pages = {813--814},
pmid = {14561424},
title = {{EGF Receptor Signaling: Putting a New Spin on Eye Development}},
volume = {13},
year = {2003}
}
@article{Zhou2000,
abstract = {Overexpression of HER-2/neu correlates with poor survival of breast and ovarian cancer patients and induces resistance to tumor necrosis factor (TNF), which causes cancer cells to escape from host immune defenses. The mechanism of HER-2/neu-induced TNF resistance is unknown. Here we report that HER-2/neu activates Akt and NF-kappaB without extracellular stimulation. Blocking of the Akt pathway by a dominant-negative Akt sensitizes the HER-2/neu-overexpressing cells to TNF-induced apoptosis and inhibits IkappaB kinases, IkappaB phosphorylation, and NF-kappaB activation. Our results suggested that HER-2/neu constitutively activates the Akt/NF-kappaB anti-apoptotic cascade to confer resistance to TNF on cancer cells and reduce host defenses against neoplasia.},
author = {Zhou, Binhua P. and Hu, Mickey C T and Miller, Stephanie A. and Yu, Zhenming and Xia, Weiya and Lin, Shiaw Yih and Hung, Mien Chie},
doi = {10.1074/jbc.275.11.8027},
isbn = {0021-9258 (Print)$\backslash$r0021-9258 (Linking)},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {10713122},
title = {{HER-2/neu blocks tumor necrosis factor-induced apoptosis via the Akt/NF- $\kappa$B pathway}},
year = {2000}
}
@article{Salcini1994,
abstract = {OBJECTIVES: This study aimed to assess the impact of the duration of organ dysfunction on the outcome of patients with severe sepsis or septic shock.$\backslash$n$\backslash$nMETHODS: Clinical data were collected from hospital charts of patients with severe sepsis and septic shock admitted to a mixed intensive care unit from November 2003 to February 2004. The duration of organ dysfunction prior to diagnosis was correlated with mortality. Results were considered significant if p{\textless}0.05.$\backslash$n$\backslash$nRESULTS: Fifty-six patients were enrolled. Mean age was 55.6+/-20.7 years, mean APACHE II score was 20.6+/-6.9, and mean SOFA score was 7.9+/-3.7. Thirty-six patients (64.3{\%}) had septic shock. The mean duration of organ dysfunction was 1.9+/-1.9 days. Within the univariate analysis, the variables correlated with hospital mortality were: age (p=0.015), APACHE II (p=0.008), onset outside the intensive care unit (p=0.05), blood glucose control (p=0.05) and duration of organ dysfunction (p=0.0004). In the multivariate analysis, only a duration of organ dysfunction persisting longer than 48 hours correlated with mortality (p=0.004, OR: 8.73 (2.37-32.14)), whereas the APACHE II score remained only a slightly significant factor (p=0.049, OR: 1.11 (1.00-1.23)). Patients who received therapeutic interventions within the first 48 hours after the onset of organ dysfunction exhibited lower mortality (32.1{\%} vs. 82.1{\%}, p=0.0001).$\backslash$n$\backslash$nCONCLUSIONS: These findings suggest that the diagnosis of organ dysfunction is not being made in a timely manner. The time elapsed between the onset of organ dysfunction and initiation of therapeutic intervention can be quite long, and this represents an important determinant of survival in cases of severe sepsis and septic shock.},
author = {Salcini, A and McGlade, J and Pelicci, G and Nicoletti, I and Pawson, T and Pelicci, P},
doi = {10.1590/S1807-59322008000400012},
issn = {1807-5932},
journal = {Oncogene},
pmid = {18719759},
title = {{Formation of Shc-Grb2 complexes is necessary to induce neoplastic transformation by overexpression of Shc proteins}},
year = {1994}
}
@article{Lachmann2016,
abstract = {UNLABELLED The accurate reconstruction of gene regulatory networks from large scale molecular profile datasets represents one of the grand challenges of Systems Biology. The Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) represents one of the most effective tools to accomplish this goal. However, the initial Fixed Bandwidth (FB) implementation is both inefficient and unable to deal with sample sets providing largely uneven coverage of the probability density space. Here, we present a completely new implementation of the algorithm, based on an Adaptive Partitioning strategy (AP) for estimating the Mutual Information. The new AP implementation (ARACNe-AP) achieves a dramatic improvement in computational performance (200× on average) over the previous methodology, while preserving the Mutual Information estimator and the Network inference accuracy of the original algorithm. Given that the previous version of ARACNe is extremely demanding, the new version of the algorithm will allow even researchers with modest computational resources to build complex regulatory networks from hundreds of gene expression profiles. AVAILABILITY AND IMPLEMENTATION A JAVA cross-platform command line executable of ARACNe, together with all source code and a detailed usage guide are freely available on Sourceforge (http://sourceforge.net/projects/aracne-ap). JAVA version 8 or higher is required. CONTACT califano@c2b2.columbia.edu SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.},
author = {Lachmann, Alexander and Giorgi, Federico M. and Lopez, Gonzalo and Califano, Andrea},
doi = {10.1093/bioinformatics/btw216},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Lachmann et al. - 2016 - ARACNe-AP Gene network reverse engineering through adaptive partitioning inference of mutual information(2).pdf:pdf},
isbn = {13674811 (Electronic)},
issn = {14602059},
journal = {Bioinformatics},
number = {14},
pages = {2233--2235},
pmid = {27153652},
title = {{ARACNe-AP: Gene network reverse engineering through adaptive partitioning inference of mutual information}},
volume = {32},
year = {2016}
}
@article{Klipp2005,
abstract = {Integration of experimental studies with mathematical modeling allows insight into systems properties, prediction of perturbation effects and generation of hypotheses for further research. We present a comprehensive mathematical description of the cellular response of yeast to hyperosmotic shock. The model integrates a biochemical reaction network comprising receptor stimulation, mitogen-activated protein kinase cascade dynamics, activation of gene expression and adaptation of cellular metabolism with a thermodynamic description of volume regulation and osmotic pressure. Simulations agree well with experimental results obtained under different stress conditions or with specific mutants. The model is predictive since it suggests previously unrecognized features of the system with respect to osmolyte accumulation and feedback control, as confirmed with experiments. The mathematical description presented is a valuable tool for future studies on osmoregulation in yeast and-with appropriate modifications-other organisms. It also serves as a starting point for a comprehensive description of cellular signaling.},
author = {Klipp, Edda and Nordlander, Bodil and Kr{\"{u}}ger, Roland and Gennemark, Peter and Hohmann, Stefan},
doi = {10.1038/nbt1114},
isbn = {1087-0156 (Print)$\backslash$r1087-0156 (Linking)},
issn = {1087-0156},
journal = {Nature Biotechnology},
number = {8},
pages = {975--982},
pmid = {16025103},
title = {{Integrative model of the response of yeast to osmotic shock}},
url = {http://www.nature.com/doifinder/10.1038/nbt1114},
volume = {23},
year = {2005}
}
@article{Murphy2006,
annote = {doi: 10.1016/j.tibs.2006.03.009},
author = {Murphy, Leon O and Blenis, John},
doi = {10.1016/j.tibs.2006.03.009},
issn = {0968-0004},
journal = {Trends in Biochemical Sciences},
month = {may},
number = {5},
pages = {268--275},
publisher = {Elsevier},
title = {{MAPK signal specificity: the right place at the right time}},
url = {https://doi.org/10.1016/j.tibs.2006.03.009},
volume = {31},
year = {2006}
}
@article{Irurzun-Arana2017,
abstract = {MOTIVATION Literature on complex diseases is abundant but not always quantitative. Many molecular pathways are qualitatively well described but this information cannot be used in traditional quantitative mathematical models employed in drug development. Tools for analysis of discrete networks are useful to capture the available information in the literature but have not been efficiently integrated by the pharmaceutical industry. We propose an expansion of the usual analysis of discrete networks that facilitates the identification/validation of therapeutic targets. RESULTS In this article, we propose a methodology to perform Boolean modeling of Systems Biology/Pharmacology networks by using SPIDDOR (Systems Pharmacology for effIcient Drug Development On R) R package. The resulting models can be used to analyze the dynamics of signaling networks associated to diseases to predict the pathogenesis mechanisms and identify potential therapeutic targets. AVAILABILITY AND IMPLEMENTATION The source code is available at https://github.com/SPIDDOR/SPIDDOR CONTACT: itzirurzun@alumni.unav.es, itroconiz@unav.esSupplementary information: Supplementary data are available at Bioinformatics online.},
author = {Irurzun-Arana, Itziar and Pastor, Jos{\'{e}} Mart{\'{i}}n and Troc{\'{o}}niz, I{\~{n}}aki F. and G{\'{o}}mez-Mantilla, Jos{\'{e}} David},
doi = {10.1093/bioinformatics/btw747},
file = {:Users/ozlem/Dropbox/papers/Boolean Models/btw747.pdf:pdf},
issn = {14602059},
journal = {Bioinformatics},
number = {7},
pages = {1040--1048},
pmid = {28073755},
title = {{Advanced Boolean modeling of biological networks applied to systems pharmacology}},
volume = {33},
year = {2017}
}
@article{Mukhopadhyay1992,
abstract = {This study characterizes the insulin-activated serine/threonine protein kinases in H4 hepatoma cells active on a 37-residue synthetic peptide (called the SKAIPS peptide) corresponding to a putative autoinhibitory domain in the carboxyl-terminal tail of the p70 S6 kinase as well as on recombinant p70 S6 kinase. Three peaks of insulin-stimulated protein kinase active on both these substrates are identified as two (possibly three) isoforms of the 40-45-kDa erk/microtubule-associated protein (MAP)-2 kinase family and a 150-kDa form of cdc2. Although distinguishable in their substrate specificity, these protein kinases together with the p54 MAP-2 kinase share a major common specificity determinant reflected in the SKAIPS peptide: the requirement for a proline residue immediately carboxyl-terminal to the site of Ser/Thr phosphorylation. In addition, however, at least one peak of insulin-stimulated protein kinase active on recombinant p70, but not on the SKAIPS peptide, is present although not yet identified. MFP/cdc2 phosphorylates both rat liver p70 S6 kinase and recombinant p70 S6 kinase exclusively at a set of Ser/Thr residues within the putative autoinhibitory (SKAIPS peptide) domain. erk/MAP kinase does not phosphorylate rat liver p70 S6 kinase, but readily phosphorylates recombinant p70 S6 kinase at sites both within and in addition to those encompassed by the SKAIPS peptide sequences. Although the tryptic 32P-peptides bearing the cdc2 and erk/MAP kinase phosphorylation sites co-migrate with a subset of the sites phosphorylated in situ in insulin-stimulated cells, phosphorylation of the p70 S6 kinase by these proline-directed protein kinases in vitro does not reproducibly activate p70 S6 kinase activity. Thus, one or more erk/MAP kinases and cdc2 are likely to participate in the insulin-induced phosphorylation of the p70 S6 kinase. In addition to these kinases, however, phosphorylation of the p70 S6 kinase by other as yet unidentified protein kinases is necessary to recapitulate the multisite phosphorylation required for activation of the p70 S6 kinase.},
author = {Mukhopadhyay, N. K. and Price, D. J. and Kyriakis, J. M. and Pelech, S. and Sanghera, J. and Avruch, J.},
isbn = {0021-9258 (Print)$\backslash$r0021-9258 (Linking)},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {1737788},
title = {{An array of insulin-activated, proline-directed serine/threonine protein kinases phosphorylate the p70 S6 kinase}},
year = {1992}
}
@article{Morris1996,
abstract = {AutoDock 2.4 predicts the bound conformations of a small, flexible ligand to a nonflexible macromolecular target of known structure. The technique combines simulated annealing for conformation searching with a rapid grid-based method of energy evaluation based on the AMBER force field. AutoDock has been optimized in performance without sacrificing accuracy; it incorporates many enhancements and additions, including an intuitive interface. We have developed a set of tools for launching and analyzing many independent docking jobs in parallel on a heterogeneous network of UNIX-based workstations. This paper describes the current release, and the results of a suite of diverse test systems. We also present the results of a systematic investigation into the effects of varying simulated-annealing parameters on molecular docking. We show that even for ligands with a large number of degrees of freedom, root-mean-square deviations of less than 1 A from the crystallographic conformation are obtained for the lowest-energy dockings, although fewer dockings find the crystallographic conformation when there are more degrees of freedom.},
author = {Morris, Garrett M and Goodsell, David S and Huey, Ruth and Olson, Arthur J},
doi = {10.1002/(SICI)1099-1352(199601)9:1&lt;1::AID-JMR241&gt;3.0.CO;2-6},
isbn = {0952-3499},
issn = {0920-654X},
journal = {Journal of computer-aided molecular design},
keywords = {Azepines,Azepines: chemistry,Azepines: metabolism,Bacterial Proteins,Bacterial Proteins: chemistry,Bacterial Proteins: metabolism,Benzamidines,Benzamidines: chemistry,Benzamidines: metabolism,Biotin,Biotin: chemistry,Biotin: metabolism,Camphor,Camphor 5-Monooxygenase,Camphor 5-Monooxygenase: chemistry,Camphor 5-Monooxygenase: metabolism,Camphor: chemistry,Camphor: metabolism,Cluster Analysis,Computer Simulation,Crystallography,HIV Protease,HIV Protease Inhibitors,HIV Protease Inhibitors: chemistry,HIV Protease Inhibitors: metabolism,HIV Protease: chemistry,HIV Protease: metabolism,Hemagglutinins,Hemagglutinins: chemistry,Hemagglutinins: metabolism,Immunoglobulin Fab Fragments,Immunoglobulin Fab Fragments: chemistry,Immunoglobulin Fab Fragments: metabolism,Ligands,Molecular Conformation,N-Acetylneuraminic Acid,N-Acetylneuraminic Acid: chemistry,N-Acetylneuraminic Acid: metabolism,Phosphorylcholine,Phosphorylcholine: chemistry,Phosphorylcholine: metabolism,Protein Binding,Protein Conformation,Software,Streptavidin,Trypsin,Trypsin: chemistry,Trypsin: metabolism,User-Computer Interface,X-Ray},
number = {4},
pages = {293--304},
pmid = {8877701},
title = {{Distributed automated docking of flexible ligands to proteins: parallel applications of AutoDock 2.4.}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/8877701},
volume = {10},
year = {1996}
}
@article{Tamas2002,
abstract = {Vav2 is a member of the Vav family that serves as a guanine nucleotide exchange factors for the Rho family of Ras-related GTPases. Unlike Vav1 whose expression is restricted to cells of hematopoietic origin, Vav2 is broadly expressed. Recently, Vav2 has been identified as a substrate for the EGF receptor, however, the mechanism by which Vav2 is activated in EGF-treated cells is unclear. By the means of an in vitro protein kinase assay, we show here that purified and activated EGF receptor phosphorylates Vav2 exclusively on its N-terminal domain. Furthermore, EGF receptor phosphorylates Vav2 on all three possible phosphorylation sites, Tyr-142, Tyr-159, and Tyr-172. In intact cells we also show that Vav2 associates with the activated EGF receptor in an SH2 domain-dependent manner, with Vav2 SH2 domain binding preferentially to autophosphorylation sites pTyr-992 and pTyr-1148 of the EGF receptor. Treatment of cells with EGF results in stimulation of exchange activity of Vav2 as measured on Rac, however, the intensity of the exchange activity does not show any correlation with the level of Vav2 tyrosine phosphorylation. Introducing a point mutation into the Vav2 PH domain or treatment of cells with the PI 3-kinase inhibitor LY294002 prior to EGF stimulation inhibits Vav2 exchange activity. While phosphorylation mutants of Vav2 can readily induce actin rearrangement in COS7 cells, PH domain mutant does not stimulate membrane ruffling. These results suggest that EGF regulates Vav2 activity basically through PI 3-kinase activation, while tyrosine phosphorylation of Vav2 may rather be necessary for mediating protein-protein interactions.},
author = {Tamas, P and Solti, Z and Bauer, P and Illes, A and Sipeki, S and Bauer, A and Farago, A and Downward, J and Buday, L},
journal = {J Biol Chem},
pmid = {12454019},
title = {{Mechanism of EGF regulation of Vav2, a guanine nucleotide exchange factor for Rac}},
year = {2002}
}
@article{Tong2006a,
abstract = {Synthetic lethality occurs when the combination of two mutations leads to an inviable organism. Screens for synthetic lethal genetic interactions have been used extensively to identify genes whose products buffer one another or impinge on the same essential pathway. For the yeast Saccharomyces cerevisiae, we developed a method termed Synthetic Genetic Array (SGA) analysis, which offers an efficient approach for the systematic construction of double mutants and enables a global analysis of synthetic lethal genetic interactions. In a typical SGA screen, a query mutation is crossed to an ordered array of approx 5000 viable gene deletion mutants (representing approximately 80{\%} of all yeast genes) such that meiotic progeny harboring both mutations can be scored for fitness defects. This array-based approach automates yeast genetic analysis in general and can be easily adapted for a number of different screens, including genetic suppression, plasmid shuffling, dosage lethality, or suppression.},
author = {Tong, A H and Boone, C},
doi = {1-59259-958-3:171 [pii]},
isbn = {1064-3745 (Print)$\backslash$r1064-3745 (Linking)},
issn = {1064-3745 (Print)},
journal = {Methods Mol Biol},
keywords = {Alleles,Base Sequence,DNA Primers/genetics,Gene Deletion,Genes, Fungal,Genes, Lethal,Genetic Techniques,Mutation,Mycology/methods,Oligonucleotide Array Sequence Analysis/instrument,Plasmids/genetics,Polymerase Chain Reaction,Saccharomyces cerevisiae/*genetics,Spores, Fungal/genetics},
pages = {171--192},
pmid = {16118434},
title = {{Synthetic genetic array analysis in Saccharomyces cerevisiae}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16118434},
volume = {313},
year = {2006}
}
@article{Kitchen2004,
abstract = {Computational approaches that 'dock' small molecules into the structures$\backslash$nof macromolecular targets and 'score' their potential complementarity$\backslash$nto binding sites are widely used in hit identification and lead optimization.$\backslash$nIndeed, there are now a number of drugs whose development was heavily$\backslash$ninfluenced by or based on structure-based design and screening strategies,$\backslash$nsuch as HIV protease inhibitors. Nevertheless, there remain significant$\backslash$nchallenges in the application of these approaches, in particular$\backslash$nin relation to current scoring schemes. Here, we review key concepts$\backslash$nand specific features of small-molecule-protein docking methods,$\backslash$nhighlight selected applications and discuss recent advances that$\backslash$naim to address the acknowledged limitations of established approaches.},
archivePrefix = {arXiv},
arxivId = {arXiv:1011.1669v3},
author = {Kitchen, Douglas B and Decornez, H{\'{e}}l{\`{e}}ne and Furr, John R and Bajorath, J{\"{u}}rgen},
doi = {10.1038/nrd1549},
eprint = {arXiv:1011.1669v3},
isbn = {1474-1776},
issn = {1474-1776},
journal = {Nat Rev Drug Discov},
keywords = {Binding Sites; Computational Biology,Molecular; Protein Binding; Structure-Activity Re,methods/trends; Drug Design; Ligands; Models},
number = {11},
pages = {935--949},
pmid = {15520816},
title = {{Docking and scoring in virtual screening for drug discovery: methods and applications.}},
url = {http://dx.doi.org/10.1038/nrd1549},
volume = {3},
year = {2004}
}
@article{Yin2014,
abstract = {We demonstrate CRISPR-Cas9-mediated correction of a Fah mutation in hepatocytes in a mouse model of the human disease hereditary tyrosinemia. Delivery of components of the CRISPR-Cas9 system by hydrodynamic injection resulted in initial expression of the wild-type Fah protein in ∼1/250 liver cells. Expansion of Fah-positive hepatocytes rescued the body weight loss phenotype. Our study indicates that CRISPR-Cas9-mediated genome editing is possible in adult animals and has potential for correction of human genetic diseases.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Yin, Hao and Xue, Wen and Chen, Sidi and Bogorad, Roman L and Benedetti, Eric and Grompe, Markus and Koteliansky, Victor and Sharp, Phillip A and Jacks, Tyler and Anderson, Daniel G},
doi = {10.1038/nbt.2884},
eprint = {NIHMS150003},
isbn = {1546-1696 (Electronic)$\backslash$r1087-0156 (Linking)},
issn = {1087-0156},
journal = {Nature Biotechnology},
number = {6},
pages = {551--553},
pmid = {24681508},
title = {{Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype}},
url = {http://www.nature.com/doifinder/10.1038/nbt.2884},
volume = {32},
year = {2014}
}
@article{Polanski2006,
abstract = {Quantitative Structure Activity Relationship (QSAR) is a term describing a variety of approaches that are of substantial interest for chemistry. This method can be defined as indirect molecular design by the iterative sampling of the chemical compounds space to optimize a certain property and thus indirectly design the molecular structure having this property. However, modeling the interactions of chemical molecules in biological systems provides highly noisy data, which make predictions a roulette risk. In this paper we briefly review the origins for this noise, particularly in multidimensional QSAR. This was classified as the data, superimposition, molecular similarity, conformational, and molecular recognition noise. We also indicated possible robust answers that can improve modeling and predictive ability of QSAR, especially the self-organizing mapping of molecular objects, in particular, the molecular surfaces, a method that was brought into chemistry by Gasteiger and Zupan.},
author = {Polanski, Jaroslaw and Bak, Andrzej and Gieleciak, Rafal and Magdziarz, Tomasz},
doi = {10.1021/ci050314b},
isbn = {1549-9596},
issn = {15499596},
journal = {Journal of Chemical Information and Modeling},
number = {6},
pages = {2310--2318},
pmid = {17125174},
title = {{Modeling robust QSAR}},
volume = {46},
year = {2006}
}
@article{Klabunde2005,
abstract = {G protein-coupled receptors (GPCRs) form a large protein family that plays an important role in many physiological and pathophysiological processes. However, the central role that the biogenic amine binding GPCRs and their ligands play in cell signaling poses a risk in new drug candidates that reveal side affinities towards these receptor sites. These candidates have the potential to interfere with the physiological signaling processes and to cause undesired effects in preclinical or clinical studies. Here, we present 3D cross-chemotype pharmacophore models for three biogenic amine antitargets: the alpha(1A) adrenergic, the 5-HT(2A) serotonin, and the D2 dopamine receptors. These pharmacophores describe the key chemical features present within these biogenic amine antagonists and rationalize the biogenic amine side affinities found for numerous new drug candidates. First applications of the alpha(1A) adrenergic receptor model reveal that these in silico tools can be used to guide the chemical optimization towards development candidates with fewer alpha(1A)-mediated side effects (for example, orthostatic hypotension) and, thus, with an improved clinical safety profile.},
author = {Klabunde, Thomas and Evers, Andreas},
doi = {10.1002/cbic.200400369},
isbn = {9783527609161},
issn = {14394227},
journal = {ChemBioChem},
keywords = {Amines,Drug design,G protein-coupled receptors,Pharmacophore modeling,Structure-activity relationship},
number = {5},
pages = {876--889},
pmid = {15791686},
title = {{GPCR antitarget modeling: Pharmacophore models for biogenic amine binding GPCRs to avoid GPCR-mediated side effects}},
volume = {6},
year = {2005}
}
@misc{Chapotin2007,
abstract = {As the United States moves toward a plant-based bioeconomy, a large research and development effort is focused on creating new feedstocks to meet biomass demand for biofuels, bioenergy, and specialized bioproducts, such as industrial compounds and biomaterial precursors. Most bioeconomy projections assume the widespread deployment of novel feedstocks developed through the use of modern molecular breeding techniques, but rarely consider the challenges involved with the use of genetically modified crops, which can include hurdles due to regulatory approvals, market adoption, and public acceptance. In this paper we consider the implications of various transgenic crops and traits under development for the bioeconomy that highlight these challenges. We believe that an awareness of the issues in crop and trait selection will allow developers to design crops with maximum stakeholder appeal and with the greatest potential for widespread adoption, while avoiding applications unlikely to meet regulatory approval or gain market and public acceptance.},
author = {Chapotin, Saharah Moon and Wolt, Jeffrey D.},
booktitle = {Transgenic Research},
doi = {10.1007/s11248-007-9122-y},
isbn = {0962-8819},
issn = {09628819},
keywords = {Biofuels,Bioproducts,Genetic engineering,Genetically modified organism,Regulatory policy},
number = {6},
pages = {675--688},
pmid = {17701080},
title = {{Genetically modified crops for the bioeconomy: Meeting public and regulatory expectations}},
volume = {16},
year = {2007}
}
@article{Sadeh2011,
abstract = {The Msn2 and Msn4 transcription factors play major roles in the yeast general stress response by mediating the transcription of hundreds of genes. Despite extensive information on Msn2/4-mediated gene expression profiles, much less is known regarding the network of proteins that regulate its activity. Here we describe a systematic approach designed to examine the roles of 35 Msn2/4 partners in regulating Msn2/4 transcriptional activity in the face of four different environmental conditions. Our analysis indicates that single deletions of 26 Msn2/4 partners significantly affect Msn2/4 transcription activity under four different conditions. The low functional redundancy of the Msn2 regulatory network indicates that Msn2/4 activity is finely tuned by many of Msn2/4 partners to provide an optimized stress response through differential activation, nuclear localization, degradation, and chromatin remodeling. Our specific analysis of Msn2 activity showed that a relatively large number of partners act to suppress Msn2 activity under nonstress conditions through independent mechanisms, including cytoplasmic retention, proteosome-mediated Msn2 degradation, and chromatin remodeling. Such negative regulation is crucial to minimize the cost of uncontrolled stress response gene expression and ensures a high growth rate in the absence of stress.},
author = {Sadeh, A. and Movshovich, N. and Volokh, M. and Gheber, L. and Aharoni, A.},
doi = {10.1091/mbc.E10-12-1007},
isbn = {9728647921},
issn = {1059-1524},
journal = {Molecular Biology of the Cell},
number = {17},
pages = {3127--3138},
pmid = {21757539},
title = {{Fine-tuning of the Msn2/4-mediated yeast stress responses as revealed by systematic deletion of Msn2/4 partners}},
url = {http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E10-12-1007},
volume = {22},
year = {2011}
}
@misc{Wang2012b,
abstract = {Mathematical modeling of biological processes provides deep insights into complex cellular systems. While quantitative and continuous models such as differential equations have been widely used, their use is obstructed in systems wherein the knowledge of mechanistic details and kinetic parameters is scarce. On the other hand, a wealth of molecular level qualitative data on individual components and interactions can be obtained from the experimental literature and high-throughput technologies, making qualitative approaches such as Boolean network modeling extremely useful. In this paper, we build on our research to provide a methodology overview of Boolean modeling in systems biology, including Boolean dynamic modeling of cellular networks, attractor analysis of Boolean dynamic models, as well as inferring biological regulatory mechanisms from high-throughput data using Boolean models. We finally demonstrate how Boolean models can be applied to perform the structural analysis of cellular networks. This overview aims to acquaint life science researchers with the basic steps of Boolean modeling and its applications in several areas of systems biology.},
author = {Wang, Rui Sheng and Saadatpour, Assieh and Albert, R{\'{e}}ka},
booktitle = {Physical Biology},
doi = {10.1088/1478-3975/9/5/055001},
isbn = {1478-3967},
issn = {14783967},
pmid = {23011283},
title = {{Boolean modeling in systems biology: An overview of methodology and applications}},
year = {2012}
}
@article{Chowdhury2009,
abstract = {Decapping is a critical step in the conserved 5'-to-3' mRNA decay pathway of eukaryotes. The hetero-octameric Lsm1-7-Pat1 complex is required for normal rates of decapping in this pathway. This complex also protects the mRNA 3'-ends from trimming in vivo. To elucidate the mechanism of decapping, we analyzed multiple lsm1 mutants, lsm1-6, lsm1-8, lsm1-9, and lsm1-14, all of which are defective in decapping and 3'-end protection but unaffected in Lsm1-7-Pat1 complex integrity. The RNA binding ability of the mutant complex was found to be almost completely lost in the lsm1-8 mutant but only partially impaired in the other mutants. Importantly, overproduction of the Lsm1-9p- or Lsm1-14p-containing (but not Lsm1-8p-containing) mutant complexes in wild-type cells led to a dominant inhibition of mRNA decay. Further, the mRNA 3'-end protection defect of lsm1-9 and lsm1-14 cells, but not the lsm1-8 cells, could be partly suppressed by overproduction of the corresponding mutant complexes in those cells. These results suggest the following: (1) Decapping requires both binding of the Lsm1-7-Pat1 complex to the mRNA and facilitation of the post-binding events, while binding per se is sufficient for 3'-end protection. (2) A major block exists at the post-binding steps in the lsm1-9 and lsm1-14 mutants and at the binding step in the lsm1-8 mutant. Consistent with these ideas, the lsm1-9, 14 allele generated by combining the mutations of lsm1-9 and lsm1-14 alleles had almost fully lost the RNA binding activity of the complex and behaved like the lsm1-8 mutant.},
author = {Chowdhury, A. and Tharun, S.},
doi = {10.1261/rna.1650109},
isbn = {1469-9001 (Electronic)},
issn = {1355-8382},
journal = {RNA},
number = {10},
pages = {1837--1848},
pmid = {19643916},
title = {{Activation of decapping involves binding of the mRNA and facilitation of the post-binding steps by the Lsm1-7-Pat1 complex}},
url = {http://rnajournal.cshlp.org/cgi/doi/10.1261/rna.1650109},
volume = {15},
year = {2009}
}
@article{Gratz2014,
abstract = {We and others recently demonstrated that the readily programmable CRISPR/Cas9 system can be used to edit the Drosophila genome. However, most applications to date have relied on aberrant DNA repair to stochastically generate frameshifting indels and adoption has been limited by a lack of tools for efficient identification of targeted events. Here we report optimized tools and techniques for expanded application of the CRISPR/Cas9 system in Drosophila through homology-directed repair (HDR) with double-stranded DNA (dsDNA) donor templates that facilitate complex genome engineering through the precise incorporation of large DNA sequences, including screenable markers. Using these donors, we demonstrate the replacement of a gene with exogenous sequences and the generation of a conditional allele. To optimize efficiency and specificity, we generated transgenic flies that express Cas9 in the germline and directly compared HDR and off-target cleavage rates of different approaches for delivering CRISPR components. We also investigated HDR efficiency in a mutant background previously demonstrated to bias DNA repair toward HDR. Finally, we developed a web-based tool that identifies CRISPR target sites and evaluates their potential for off-target cleavage using empirically rooted rules. Overall, we have found that injection of a dsDNA donor and guide RNA-encoding plasmids into vasa-Cas9 flies yields the highest efficiency HDR and that target sites can be selected to avoid off-target mutations. Efficient and specific CRISPR/Cas9-mediated HDR opens the door to a broad array of complex genome modifications and greatly expands the utility of CRISPR technology for Drosophila research.},
author = {Gratz, Scott J. and Ukken, Fiona P. and Rubinstein, C. Dustin and Thiede, Gene and Donohue, Laura K. and Cummings, Alexander M. and Oconnor-Giles, Kate M.},
doi = {10.1534/genetics.113.160713},
isbn = {1943-2631 (Electronic)$\backslash$n0016-6731 (Linking)},
issn = {19432631},
journal = {Genetics},
number = {4},
pages = {961--971},
pmid = {24478335},
title = {{Highly specific and efficient CRISPR/Cas9-catalyzed homology-directed repair in Drosophila}},
volume = {196},
year = {2014}
}
@article{Ikner2005,
abstract = {Oxidative stress that generates the reactive oxygen species (ROS) is one of the major causes of DNA damage and mutations. The "DNA damage checkpoint" that arrests cell cycle and repairs damaged DNA has been a focus of recent studies, and the genetically amenable model systems provided by yeasts have been playing a leading role in the eukaryotic checkpoint research. However, means to eliminate ROS are likely to be as important as the DNA repair mechanisms in order to suppress mutations in the chromosomal DNA, and yeasts also serve as excellent models to understand how eukaryotes combat oxidative stress. In this article, we present an overview of the signaling pathways that sense oxidative stress and induce expression of various anti-oxidant genes in the budding yeast Saccharomyces cerevisiae, the fission yeast Schizosaccharomyces pombe and the pathogenic yeast Candida albicans. Three conserved signaling modules have been identified in the oxidative stress response of these diverse yeast species: the stress-responsive MAP kinase cascade, the multistep phosphorelay and the AP-1-like transcription factor. The structure and function of these signaling modules are discussed.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Ikner, Aminah and Shiozaki, Kazuhiro},
doi = {10.1016/j.mrfmmm.2004.09.006},
eprint = {NIHMS150003},
isbn = {0027-5107 (Print)$\backslash$r0027-5107 (Linking)},
issn = {0027-5107},
journal = {Mutation research},
keywords = {Mitogen-Activated Protein Kinases,Mitogen-Activated Protein Kinases: genetics,Mitogen-Activated Protein Kinases: metabolism,Oxidative Stress,Oxidative Stress: genetics,Phosphorylation,Reactive Oxygen Species,Reactive Oxygen Species: metabolism,Signal Transduction,Signal Transduction: genetics,Transcription Factor AP-1,Transcription Factor AP-1: genetics,Transcription Factor AP-1: metabolism,Transcriptional Activation,Yeasts,Yeasts: enzymology,Yeasts: genetics,Yeasts: metabolism},
number = {1-2},
pages = {13--27},
pmid = {15603750},
title = {{Yeast signaling pathways in the oxidative stress response.}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15603750},
volume = {569},
year = {2005}
}
@article{Narsis2015,
author = {Narsis, A and Ioannis, N and Leonidas, G and Manuel, Jose},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Narsis et al. - 2015 - Signaling networks in MS A systems-based approach to developing new pharmacological therapies Signaling networks.pdf:pdf},
pages = {138--146},
title = {{Signaling networks in MS : A systems-based approach to developing new pharmacological therapies Signaling networks in MS : A systems based approach to developing new pharmacological therapies * Both authors contributed equally Institute Biomedical Researc}},
volume = {21},
year = {2015}
}
@article{Yuh1998,
abstract = {The genomic regulatory network that controls gene expression ultimately determines form and function in each species. The operational nature of the regulatory programming specified in cis-regulatory DNA sequence was determined from a detailed functional analysis of a sea urchin control element that directs the expression of a gene in the endoderm during development. Spatial expression and repression, and the changing rate of transcription of this gene, are mediated by a complex and extended cis-regulatory system. The system may be typical of developmental cis-regulatory apparatus. All of its activities are integrated in the proximal element, which contains seven target sites for DNA binding proteins. A quantitative computational model of this regulatory element was constructed that explicitly reveals the logical interrelations hard-wired into the DNA.},
author = {Yuh, Chiou H. and Bolouri, Hamid and Davidson, Eric H.},
doi = {10.1126/science.279.5358.1896},
isbn = {0036-8075 (Print) 0036-8075 (Linking)},
issn = {00368075},
journal = {Science},
pmid = {9506933},
title = {{Genomic cis-regulatory logic: Experimental and computational analysis of a sea urchin gene}},
year = {1998}
}
@article{Sauce2018,
author = {Sauce, Bruno and Bendrath, Sophie and Herzfeld, Margalit and Siegel, Daniel and Style, Connor and Rab, Sayeeda and Korabelnikov, Jonathan and Matzel, Louis},
doi = {10.1098/RSTB.2017.0289},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Sauce et al. - 2018 - Substantial heritability and malleability of general cognitive ability revealed in a mouse analogue of a twin adop.pdf:pdf},
isbn = {0000000304627},
issn = {0962-8436},
journal = {Philos. Trans. R. Soc. B Biol. Sci},
keywords = {behaviour,cognition,genetics},
number = {September},
pages = {(This Issue)},
pmid = {30104434},
title = {{Substantial heritability and malleability of general cognitive ability revealed in a mouse analogue of a twin adoption study}},
year = {2018}
}
@article{Mussel2010c,
abstract = {Motivation: As the study of information processing in living cells moves from individual pathways to complex regulatory networks, mathematical models and simulation become indispensable tools for analyzing the complex behavior of such networks and can provide deep insights into the functioning of cells. The dynamics of gene expression, for example, can be modeled with Boolean networks (BNs). These are mathematical models of low complexity, but have the advantage of being able to capture essential properties of gene-regulatory networks. However, current implementations of BNs only focus on different sub-aspects of this model and do not allow for a seamless integration into existing preprocessing pipelines. Results: BoolNet efficiently integrates methods for synchronous, asynchronous and probabilistic BNs. This includes reconstructing networks from time series, generating random networks, robustness analysis via perturbation, Markov chain simulations, and identification and visualization of attractors. Availability: The package BoolNet is freely available from the R project at},
archivePrefix = {arXiv},
arxivId = {http://arxiv.org/abs/1604.02208},
author = {M{\"{u}}ssel, Christoph and Hopfensitz, Martin and Kestler, Hans A.},
doi = {10.1093/bioinformatics/btq124},
eprint = {/arxiv.org/abs/1604.02208},
isbn = {1367-4811 (Linking)},
issn = {13674803},
journal = {Bioinformatics},
pmid = {20378558},
primaryClass = {http:},
title = {{BoolNet-an R package for generation, reconstruction and analysis of Boolean networks}},
year = {2010}
}
@book{Back2014,
abstract = {The analysis of complex biological networks has traditionally relied$\backslash$non decomposition into smaller, semi-autonomous units such as individual$\backslash$nsignaling pathways. With the increased scope of systems biology (models),$\backslash$nrational approaches to modularization have become an important topic.$\backslash$nWith increasing acceptance of $\backslash$emph{\{}de facto{\}} modularity in biology,$\backslash$nwidely different definitions of what constitutes a module have sparked$\backslash$ncontroversies. Here, we therefore review prominent classes of modular$\backslash$napproaches based on formal network representations. Despite some$\backslash$npromising research directions, several important theoretical challenges$\backslash$nremain open on the way to formal, function-centered modular decompositions$\backslash$nfor dynamic biological networks. Modular Analysis of Biological Networks Modeling Signaling Networks Using High-throughput Phospo-proteomics An Integrated Bayesian Framework for Identifying Phosphorylation Networks in Stimulated Cells Signaling Cascades: Consequences of Varying Substrate and Phosphatase Levels Heterogeneous Biological Network Visualization System: Case Study in Context ofMedical Image Data Evolution of the Cognitive Proteome: From Static to Dynamic Network Models Molecular Systems Biology of Sic1 in Yeast Cell Cycle Regulation ThroughMultiscaleModeling Regulatory Dynamics for the Differentiation of Mouse Embryonic Stem Cells Using PriorKnowledge ......................... 247 Dominik Lutter, Philipp Bruns, and Fabian J. Theis 15 Cell Death and Life in Cancer:MathematicalModeling of Cell Fate Decisions....................................................... 261 Andrei Zinovyev, Simon Fourquet, Laurent Tournier, Laurence Calzone, and Emmanuel Barillot 16 Theoretical Aspects of Cellular Decision-Making and Information-Processing ............................................... 275 Tetsuya J. Kobayashi and Atsushi Kamimura 17 Zooming in on Yeast Osmoadaptation ................................... 293 Clemens K¨ uhn and Edda Klipp},
author = {Back, Nathan and Cohen, Irun R and Lajtha, Abel and Lambris, John D and Paoletti, Rodolfo},
booktitle = {Experimental physiology},
doi = {10.1113/expphysiol.2014.1337},
isbn = {9781441972095},
issn = {1469-445X},
pmid = {25100797},
title = {{Advances in Systems Biology}},
year = {2014}
}
@misc{Bessman1996,
abstract = {Our studies on the biochemical basis of spontaneous mutations took an interesting and unexpected turn when we discovered that a small region of amino acid homology between the MutT protein of Escherichia coli and the MutX protein of Streptococcus pneumoniae was involved in their nucleoside triphosphatase as well as their antimutator activities (1–3). Computer searches of the data banks revealed that this same small conserved region was present in a number of other proteins in organisms ranging from viruses to humans (2, 4). Most of these proteins containing the signature are coded for by open reading frames (orfs) 1 whose products are either unidentified or of unknown function. We have been attempting, systematically, to identify and characterize enzymatic activities associated with these proteins, and it is now evident that nature has adopted this motif, originally identified as the active site of the nucleoside-triphosphate pyrophosphohydrolase of MutT (5, 6), and adapted it for use in many diverse reactions distinct from its function in the MutT protein. This short review summarizes our present knowledge of those reactions catalyzed by proteins harbor-ing the MutT signature sequence and calls attention to a unique and versatile nucleotide binding and catalytic site. Although it might appear that the enzymes of this family act upon a wide variety of unrelated substrates, those characterized so far all hy-drolyze a nucleoside diphosphate linked to some other moiety, X. For convenience, and to correct a misapprehension, we propose the mnemonic " nudix " hydrolase for this family of enzymes to replace the " MutT family. " Currently, this signature sequence is desig-nated the " MutT pattern " in version 13.0 of the PROSITE data base of amino acid sequence motifs (7). This initial classification is misleading, because many, if not most, of these proteins are not involved directly in preventing mutations nor do they catalyze the archetypal nucleoside triphosphate pyrophosphohydrolysis reac-tion originally described for MutT itself (5, 6). The MutT Prototype Characterization of the E. coli MutT protein, the progenitor of the family, followed from studies designed to elucidate the bio-chemical basis of the mutT mutator phenotype. Treffers et al. (8) originally described a mutant strain of E. coli, mutT1, with spon-taneous mutation frequencies ranging from 100-to 10,000-fold higher than normal. Yanofsky et al. (9) showed that unlike typical defective mutator genes causing a variety of derangements in DNA such as transitions, transversions, frameshifts, etc., mutT causes, exclusively, a single, unidirectional AT 3 CG transversion. This could be explained by either or both of the following base mispair-ing events during DNA replication.},
author = {Bessman, Maurice J. and Frick, David N. and O'Handley, Suzanne F.},
booktitle = {Journal of Biological Chemistry},
doi = {10.1074/jbc.271.41.25059},
isbn = {4105167316},
issn = {00219258},
number = {41},
pages = {25059--25062},
pmid = {8810257},
title = {{The MutT proteins or 'Nudix' hydrolases, a family of versatile, widely distributed, 'housecleaning' enzymes}},
volume = {271},
year = {1996}
}
@article{Graus-Porta1997a,
abstract = {We have analyzed ErbB receptor interplay induced by the epidermal growth factor (EGF)-related peptides in cell lines naturally expressing the four ErbB receptors. Down-regulation of cell surface ErbB-1 or ErbB-2 by intracellular expression of specific antibodies has allowed us to delineate the role of these receptors during signaling elicited by: EGF and heparin binding EGF (HB-EGF), ligands of ErbB-1; betacellulin (BTC), a ligand of ErbB-1 and ErbB-4; and neu differentiation factor (NDF), a ligand of ErbB-3 and ErbB-4. Ligand-induced ErbB receptor heterodimerization follows a strict hierarchy and ErbB-2 is the preferred heterodimerization partner of all ErbB proteins. NDF-activated ErbB-3 or ErbB-4 heterodimerize with ErbB-1 only when no ErbB-2 is available. If all ErbB receptors are present, NDF receptors preferentially dimerize with ErbB-2. Furthermore, EGF- and BTC-induced activation of ErbB-3 is impaired in the absence of ErbB-2, suggesting that ErbB-2 has a role in the lateral transmission of signals between other ErbB receptors. Finally, ErbB-1 activated by all EGF-related peptides (EGF, HB-EGF, BTC and NDF) couples to SHC, whereas only ErbB-1 activated by its own ligands associates with and phosphorylates Cbl. These results provide the first biochemical evidence that a given ErbB receptor has distinct signaling properties depending on its dimerization.},
author = {Graus-Porta, Diana and Beerli, Roger R. and Daly, John M. and Hynes, Nancy E.},
doi = {10.1093/emboj/16.7.1647},
isbn = {0261-4189 (Print)},
issn = {02614189},
journal = {EMBO Journal},
keywords = {ErbB receptors,Lateral signaling,Receptor dimerization,Signal transduction,Single chain antibody},
pmid = {9130710},
title = {{ErbB-2, the preferred heterodimerization partner of all ErbB receptors, is a mediator of lateral signaling}},
year = {1997}
}
@article{Tong2006b,
abstract = {Synthetic lethality occurs when the combination of two mutations leads to an inviable organism. Screens for synthetic lethal genetic interactions have been used extensively to identify genes whose products buffer one another or impinge on the same essential pathway. For the yeast Saccharomyces cerevisiae, we developed a method termed Synthetic Genetic Array (SGA) analysis, which offers an efficient approach for the systematic construction of double mutants and enables a global analysis of synthetic lethal genetic interactions. In a typical SGA screen, a query mutation is crossed to an ordered array of approx 5000 viable gene deletion mutants (representing approximately 80{\%} of all yeast genes) such that meiotic progeny harboring both mutations can be scored for fitness defects. This array-based approach automates yeast genetic analysis in general and can be easily adapted for a number of different screens, including genetic suppression, plasmid shuffling, dosage lethality, or suppression.},
author = {Tong, Amy Hin Yan and Boone, Charles},
issn = {1064-3745},
journal = {Methods in molecular biology},
keywords = {Alleles,Base Sequence,DNA Primers,DNA Primers: genetics,Fungal,Fungal: genetics,Gene Deletion,Genes,Genetic Techniques,Lethal,Mutation,Mycology,Mycology: methods,Oligonucleotide Array Sequence Analysis,Oligonucleotide Array Sequence Analysis: instrumen,Oligonucleotide Array Sequence Analysis: methods,Plasmids,Plasmids: genetics,Polymerase Chain Reaction,Saccharomyces cerevisiae,Saccharomyces cerevisiae: genetics,Spores},
pages = {171--92},
pmid = {16118434},
title = {{Synthetic genetic array analysis in Saccharomyces cerevisiae.}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/16118434},
volume = {313},
year = {2006}
}
@article{Forli2016,
abstract = {Computational docking can be used to predict bound conformations and free energies of binding for small-molecule ligands to macromolecular targets. Docking is widely used for the study of biomolecular interactions and mechanisms, and it is applied to structure-based drug design. The methods are fast enough to allow virtual screening of ligand libraries containing tens of thousands of compounds. This protocol covers the docking and virtual screening methods provided by the AutoDock suite of programs, including a basic docking of a drug molecule with an anticancer target, a virtual screen of this target with a small ligand library, docking with selective receptor flexibility, active site prediction and docking with explicit hydration. The entire protocol will require ∼5 h.},
archivePrefix = {arXiv},
arxivId = {15334406},
author = {Forli, Stefano and Huey, Ruth and Pique, Michael E and Sanner, Michel F and Goodsell, David S and Olson, Arthur J},
doi = {10.1038/nprot.2016.051},
eprint = {15334406},
isbn = {0032-3896 1349-0540},
issn = {1750-2799},
journal = {Nature protocols},
number = {5},
pages = {905--19},
pmid = {27077332},
title = {{Computational protein-ligand docking and virtual drug screening with the AutoDock suite.}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/27077332{\%}0Ahttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC4868550},
volume = {11},
year = {2016}
}
@misc{Bruggeman2007,
abstract = {The advent of functional genomics has enabled the molecular biosciences to come a long way towards characterizing the molecular constituents of life. Yet, the challenge for biology overall is to understand how organisms function. By discovering how function arises in dynamic interactions, systems biology addresses the missing links between molecules and physiology. Top-down systems biology identifies molecular interaction networks on the basis of correlated molecular behavior observed in genome-wide 'omics' studies. Bottom-up systems biology examines the mechanisms through which functional properties arise in the interactions of known components. Here, we outline the challenges faced by systems biology and discuss limitations of the top-down and bottom-up approaches, which, despite these limitations, have already led to the discovery of mechanisms and principles that underlie cell function. {\textcopyright} 2006 Elsevier Ltd. All rights reserved.},
author = {Bruggeman, Frank J. and Westerhoff, Hans V.},
booktitle = {Trends in Microbiology},
doi = {10.1016/j.tim.2006.11.003},
isbn = {0966-842X},
issn = {0966842X},
pmid = {17113776},
title = {{The nature of systems biology}},
year = {2007}
}
@article{Turkson1998,
abstract = {While signal transducers and activators of transcription (STATs) were originally discovered as intracellular effectors of normal signaling by cytokines, increasing evidence also points to a role for STAT transcription factors in oncogenesis. Previous studies have demonstrated that one STAT family member, Stat3, possesses constitutively elevated tyrosine phosphorylation and DNA-binding activity in fibroblasts stably transformed by the Src oncoprotein. To determine if this Stat3 activation by Src could induce Stat3-mediated gene expression, luciferase reporter constructs based on synthetic and authentic promoters were transfected into NIH 3T3 cells. Activation of endogenous cellular Stat3 by the Src oncoprotein induced gene expression through a Stat3-specific binding element (TTCCCGAA) of the C-reactive protein gene promoter. A naturally occurring splice variant of human Stat3 protein, Stat3beta, with a deletion in the C-terminal transactivation domain abolished this gene induction in a dominant negative manner. Expression of Stat3beta did not have any effect on a reporter construct based on the c-fos serum response element, which is not dependent on Stat3 signaling, indicating that Stat3beta does not nonspecifically inhibit other signaling pathways or Src function. Transfection of vectors expressing Stat3beta together with Src blocked cell transformation by Src as measured in a quantitative focus formation assay using NIH 3T3 cells. By contrast, Stat3beta had a much less pronounced effect on focus formation induced by the Ras oncoprotein, which does not activate Stat3 signaling. In addition, three independent clones of NIH 3T3 cells stably overexpressing Stat3beta were generated and characterized, demonstrating that Stat3beta overexpression does not have a toxic effect on cell viability. These Stat3beta-overexpressing clones were shown to be deficient in Stat3-mediated signaling and refractory to Src-induced cell transformation. We conclude that Stat3 activation by the Src oncoprotein leads to specific gene regulation and that Stat3 is one of the critical signaling pathways involved in Src oncogenesis. Our findings provide evidence that oncogenesis-associated activation of Stat3 signaling is part of the process of malignant transformation.},
author = {Turkson, James and Bowman, Tammy and Garcia, Roy and Caldenhoven, Eric and {De Groot}, Rolf P. and Jove, Richard},
doi = {10.1128/MCB.18.5.2545},
isbn = {0270-7306 (Print)$\backslash$r0270-7306 (Linking)},
issn = {0270-7306},
journal = {Mol. Cell. Biol.},
pmid = {9566874},
title = {{Stat3 Activation by Src Induces Specific Gene Regulation and Is Required for Cell Transformation}},
year = {1998}
}
@article{Stokoe1992,
abstract = {MAP kinase-activated protein kinase-2 (MAPKAP kinase-2) phosphorylates the serine residues in murine heat shock protein 25 (hsp25) and human heat shock protein 27 (hsp27) which are phosphorylated in vivo in response to growth factors and heat shock, namely Ser15 and Ser40 (hsp25) and Ser15, Ser78 and Ser82 (hsp27). Se86 of hsp25 and the equivalent residue in hsp27 (Ser82) are phosphorylated preferentially in vitro. The small heat shock protein is present in rabbit skeletal muscle and hsp25 kinase activity in skeletal muscle extracts co-purifies with MAPKAP kinase-2 activity throughout the purification of the latter enzyme. These results suggest that MAPKAP kinase-2 is the enzyme responsible for the phosphorylation of these small heat shock proteins in mammalian cells. {\textcopyright} 1992.},
author = {Stokoe, David and Engel, Katrin and Campbell, David G. and Cohen, Philip and Gaestel, Matthias},
doi = {10.1016/0014-5793(92)81216-9},
isbn = {0014-5793 (Print)$\backslash$r0014-5793},
issn = {00145793},
journal = {FEBS Letters},
pmid = {1332886},
title = {{Identification of MAPKAP kinase 2 as a major enzyme responsible for the phosphorylation of the small mammalian heat shock proteins}},
year = {1992}
}
@article{Cong2013,
abstract = {Functional elucidation of causal genetic variants and elements requires precise genome editing technologies. The type II prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)/Cas adaptive immune system has been shown to facilitate RNA-guided site-specific DNA cleavage. We engineered two different type II CRISPR/Cas systems and demonstrate that Cas9 nucleases can be directed by short RNAs to induce precise cleavage at endogenous genomic loci in human and mouse cells. Cas9 can also be converted into a nicking enzyme to facilitate homology-directed repair with minimal mutagenic activity. Lastly, multiple guide sequences can be encoded into a single CRISPR array to enable simultaneous editing of several sites within the mammalian genome, demonstrating easy programmability and wide applicability of the RNA-guided nuclease technology.},
archivePrefix = {arXiv},
arxivId = {arXiv:1106.5958},
author = {Cong, Le and Ran, F Ann and Cox, David and Lin, Shuailiang and Barretto, Robert and Habib, Naomi and Hsu, Patrick D and Wu, Xuebing and Jiang, Wenyan and Marraffini, Luciano A and Zhang, Feng and Porteus, M. H. and Baltimore, D. and Miller, J. C. and Sander, J. D. and Wood, A. J. and Christian, M. and Zhang, Feng and Miller, J. C. and Reyon, D. and Boch, J. and Moscou, M. J. and Bogdanove, A. J. and Stoddard, B. L. and Jinek, M. and Gasiunas, G. and Barrangou, R. and Horvath, P. and Siksnys, V. and Garneau, J. E. and Deveau, H. and Garneau, J. E. and Moineau, S. and Horvath, P. and Barrangou, R. and Makarova, K. S. and Bhaya, D. and Davison, M. and Barrangou, R. and Deltcheva, E. and Sapranauskas, R. and Magad{\'{a}}n, A. H. and Dupuis, M. E. and Villion, M. and Moineau, S. and Deveau, H. and Mojica, F. J. and D{\'{i}}ez-Villase{\~{n}}or, C. and Garc{\'{i}}a-Mart{\'{i}}nez, J. and Almendros, C. and Jinek, M. and Doudna, J. A. and Malone, C. D. and Hannon, G. J. and Meister, G. and Tuschl, T. and Certo, M. T. and Mali, P. and Carr, P. A. and Church, G. M. and Barrangou, R. and Horvath, P. and Brouns, S. J. and Guschin, D. Y.},
doi = {10.1126/science.1231143},
eprint = {arXiv:1106.5958},
isbn = {9780874216561},
issn = {1095-9203},
journal = {Science (New York, N.Y.)},
number = {6121},
pages = {819--23},
pmid = {23287718},
title = {{Multiplex genome engineering using CRISPR/Cas systems.}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/23287718{\%}5Cnhttp://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=PMC3795411},
volume = {339},
year = {2013}
}
@article{Guelzim2002,
abstract = {Interpretation of high-throughput biological data requires a knowledge of the design principles underlying the networks that sustain cellular functions. Of particular importance is the genetic network, a set of genes that interact through directed transcriptional regulation. Genes that exert a regulatory role encode dedicated transcription factors (hereafter referred to as regulating proteins) that can bind to specific DNA control regions of regulated genes to activate or inhibit their transcription. Regulated genes may themselves act in a regulatory manner, in which case they participate in a causal pathway. Looping pathways form feedback circuits. Because a gene can have several connections, circuits and pathways may crosslink and thus represent connected components. We have created a graph of 909 genetically or biochemically established interactions among 491 yeast genes. The number of regulating proteins per regulated gene has a narrow distribution with an exponential decay. The number of regulated genes per regulating protein has a broader distribution with a decay resembling a power law. Assuming in computer-generated graphs that gene connections fulfill these distributions but are otherwise random, the local clustering of connections and the number of short feedback circuits are largely underestimated. This deviation from randomness probably reflects functional constraints that include biosynthetic cost, response delay and differentiative and homeostatic regulation.},
author = {Guelzim, N and Bottani, S and Bourgine, P and Kepes, F},
doi = {10.1038/ng873\rng873 [pii]},
isbn = {1061-4036 (Print)$\backslash$r1061-4036 (Linking)},
journal = {Nat Genet},
keywords = {*Transcription, Genetic,Gene Expression Regulation, Fungal,Genes, Fungal,Genes, Regulator,Models, Genetic,Saccharomyces cerevisiae/*genetics},
pmid = {11967534},
title = {{Topological and causal structure of the yeast transcriptional regulatory network}},
year = {2002}
}
@article{Jones1999a,
abstract = {ErbB receptor activation is a complex process and is dependent upon the type and number of receptors expressed on a given cell. Previous studies with defined combinations of ErbB receptors expressed in mammalian cells have helped elucidate specific biological responses for many of the recognized gene products that serve as ligands for these receptors. However, no study has examined the binding of these ligands in a defined experimental system. To address this issue, the relative binding affinities of the egf domains of eleven ErbB ligands were measured on six ErbB receptor combinations using a soluble receptor-ligand binding format. The ErbB2/4 heterodimer was shown to bind all ligands tested with moderate to very high affinity. In contrast, ErbB3 showed much more restrictive ligand binding specificity and measurable binding was observed only with heregulin, neuregulin2$\beta$, epiregulin and the synthetic heregulin/egf chimera, biregulin. These studies also revealed that ErbB2 preferentially enhances ligand binding to ErbB3 or ErbB4 and to a lesser degree to ErbB1. Copyright (C) 1999 Federation of European Biochemical Societies.},
author = {Jones, Jennifer T. and Akita, Robert W. and Sliwkowski, Mark X.},
doi = {10.1016/S0014-5793(99)00283-5},
isbn = {0014-5793 (Print)$\backslash$n0014-5793 (Linking)},
issn = {00145793},
journal = {FEBS Letters},
keywords = {ErbB receptor and ligand,ErbB2-containing heterodimer,Neuregulin},
pmid = {10214951},
title = {{Binding specificities and affinities of egf domains for ErbB receptors}},
year = {1999}
}
@article{Bonnet2013,
author = {Bonnet, Eric and Calzone, Laurence and Rovera, Daniel and Stoll, Gautier and Barillot, Emmanuel},
file = {:Users/ozlem/Desktop/Tools/BiNoM{\_}Manual{\_}v2.pdf:pdf},
title = {{BiNoM : A Biological Network Manager Manual}},
year = {2013}
}
@article{Mason2014,
abstract = {RAD51 is the central protein that catalyzes DNA repair via homologous recombination (HR), a process that ensures genomic stability. RAD51 protein is commonly expressed at high levels in cancer cells relative to their non-cancerous precursors. High levels of RAD51 expression can lead to the formation of genotoxic RAD51 protein complexes on undamaged chromatin. We developed a therapeutic approach that exploits this potentially toxic feature of malignancy, using compounds that stimulate the DNA binding activity of RAD51 to promote cancer cell death. A panel of immortalized cell lines was challenged with the RAD51-stimulatory compound RS-1. Resistance to RS-1 tended to occur in cells with higher levels of RAD54L and RAD54B, which are Swi2/Snf2-related translocases known to dissociate RAD51 filaments from double-stranded DNA. In PC3 prostate cancer cells, RS-1 induced lethality was accompanied by the formation of microscopically visible RAD51 nuclear protein foci occurring in the absence of any DNA-damaging treatment. Treatment with RS-1 promoted significant anti-tumor responses in a mouse model, providing proof of principle for this novel therapeutic strategy.},
author = {Mason, Jennifer M. and Logan, Hillary L. and Budke, Brian and Wu, Megan and Pawlowski, Michal and Weichselbaum, Ralph R. and Kozikowski, Alan P. and Bishop, Douglas K. and Connell, Philip P.},
doi = {10.1158/0008-5472.CAN-13-3220},
isbn = {7738348119},
issn = {15387445},
journal = {Cancer Research},
number = {13},
pages = {3546--3555},
pmid = {24753542},
title = {{The rad51-stimulatory compound rs-1 can exploit the rad51 overexpression that exists in cancer cells and tumors}},
volume = {74},
year = {2014}
}
@misc{Downward1998,
abstract = {Activated Ras proteins have either positive or negative effects on the regulation of apoptosis depending on cell type and other factors. In part, this is due to the ability of Ras to control directly multiple effector pathways, including PI3-kinase, which provides a universal survival signal, and Raf, which can inhibit survival. The mechanisms remain partly unclear, however, especially with regard to Raf effects on apoptosis regulation. Recently Ras has been shown to be able to protect cells from apoptosis either through activation of PKB/Akt via PI3-kinase, or through activation of NF-$\kappa$B.},
author = {Downward, Julian},
booktitle = {Current Opinion in Genetics and Development},
doi = {10.1016/S0959-437X(98)80061-0},
isbn = {0959-437X (Print) 0959-437X (Linking)},
issn = {0959437X},
pmid = {9529605},
title = {{Ras signalling and apoptosis}},
year = {1998}
}
@article{MacCallum2000,
abstract = {This chapter presents a review of applications of structural equation modeling (SEM) published in psychological research journals in recent years. We focus first on the variety of research designs and substantive issues to which SEM can be applied productively. We then discuss a number of methodological problems and issues of concern that characterize some of this literature. Although it is clear that SEM is a powerful tool that is being used to great benefit in psychological research, it is also clear that the applied SEM literature is characterized by some chronic problems and that this literature can be considerably improved by greater attention to these issues.},
author = {MacCallum, Robert C. and Austin, James T.},
doi = {10.1146/annurev.psych.51.1.201},
file = {:Users/ozlem/Desktop/SEM/Application of SEM in Physiological Research.pdf:pdf},
isbn = {0066-4308},
issn = {0066-4308},
journal = {Annual Review of Psychology},
keywords = {a review of applications,abstract this chapter presents,and substantive issues to,covariance structures,focus first on the,journals in recent years,lisrel,modeling,of structural equation,published in psychological research,sem,structural equation models,variety of research designs,we,which sem},
number = {1},
pages = {201--226},
pmid = {10751970},
title = {{Applications of Structural Equation Modeling in Psychological Research}},
volume = {51},
year = {2000}
}
@article{Zerbino2009,
abstract = {Recent advances in sequencing technology made it possible to gen- erate vast amounts of sequence data. The fragments produced by these high-throughput methods are, however, far shorter than in traditional Sanger sequencing. Previously, micro-reads of less than 50 base pairs were considered useful only in the presence of an existing assembly. This thesis describes solutions for assembling short read sequencing data de novo, in the absence of a reference genome. The algorithms developed here are based on the de Bruijn graph. This data structure is highly suitable for the assembly and comparison of genomes for the following reasons. It provides a flexible tool to han- dle the sequence variants commonly found in genome evolution such as duplications, inversions or transpositions. In addition, it can com- bine sequences of highly different lengths, from short reads to assembled genomes. Finally, it ensures an effective data compression of highly re- dundant datasets. This thesis presents the development of a collection of methods, called Velvet, to convert a de Bruijn graph into a traditional assembly of contiguous sequences. The first step of the process, termed Tour Bus, re- moves sequencing errors and handles biological variations such as poly- morphisms. In its second part, Velvet aims to resolve repeats based on the available information, from low coverage long reads (Rock Band) or paired shotgun reads (Pebble). These methods were tested on various sim- ulations for precision and efficiency, then on control experimental datasets. De Bruijn graphs can also be used to detect and analyse structural variants from unassembled data. The final chapter of this thesis presents the results of collaborative work on the analysis of several experimental unassembled datasets.},
author = {Zerbino, Daniel Robert},
doi = {10.1016/j.isprsjprs.2006.12.001},
isbn = {0924-2716},
issn = {09242716},
journal = {Molecular Biology},
pages = {149},
title = {{Genome assembly and comparison using de Bruijn graphs}},
year = {2009}
}
@misc{Tomicic2013,
abstract = {Topoisomerase I (TOP1) inhibitors applied in cancer therapy such as topotecan and irinotecan are derivatives of the natural alkaloid camptothecin (CPT). The mechanism of CPT poisoning of TOP1 rests on inhibition of the re-ligation function of the enzyme resulting in the stabilization of the TOP1-cleavable complex. In the presence of CPTs this enzyme-DNA complex impairs transcription and DNA replication, resulting in fork stalling and the formation of DNA double-strand breaks (DSB) in proliferating cells. As with most chemotherapeutics, intrinsic and acquired drug resistance represents a hurdle that limits the success of CPT therapy. Preclinical data indicate that resistance to CPT-based drugs might be caused by factors such as (a) poor drug accumulation in the tumor, (b) high rate of drug efflux, (c) mutations in TOP1 leading to failure in CPT docking, or (d) altered signaling triggered by the drug-TOP1-DNA complex, (e) expression of DNA repair proteins, and (f) failure to activate cell death pathways. This review will focus on the issues (d-f). We discuss degradation of TOP1 as part of the repair pathway in the processing of TOP1 associated DNA damage, give a summary of proteins involved in repair of CPT-induced replication mediated DSB, and highlight the role of p53 and inhibitors of apoptosis proteins (IAPs), particularly XIAP and survivin, in cancer cell resistance to CPT-like chemotherapeutics. ?? 2012 Elsevier B.V.},
author = {Tomicic, Maja T. and Kaina, Bernd},
booktitle = {Biochimica et Biophysica Acta - Reviews on Cancer},
doi = {10.1016/j.bbcan.2012.09.002},
isbn = {0006-3002 (Print)$\backslash$r0006-3002 (Linking)},
issn = {0304419X},
keywords = {Cancer cell resistance,DSB repair,P53,Survivin,Topoisomerase I inhibitors,XIAP},
number = {1},
pages = {11--27},
pmid = {23006513},
title = {{Topoisomerase degradation, DSB repair, p53 and IAPs in cancer cell resistance to camptothecin-like topoisomerase I inhibitors}},
volume = {1835},
year = {2013}
}
@misc{Irwin2008,
abstract = {The ZINC database of commercially available compounds contains biologically relevant representations of purchasable compounds in ready-to-screen formats. ZINC uses catalogs from over 50 compound vendors, changing from time to time to reflect newly available compounds and depleted stock. ZINC is available in subsets that reflect current opinion in the field such as "fragment-like" and "lead-like," and has a facility to create additional small ad hoc subsets. ZINC has a search facility, as well as a service to process molecules that are not in ZINC by uploading them to a server.},
author = {Irwin, John J.},
booktitle = {Current Protocols in Bioinformatics},
doi = {10.1002/0471250953.bi1406s22},
isbn = {0471250953},
issn = {19343396},
keywords = {Ligand discovery,Molecular docking,Small molecule libraries,Virtual screening},
number = {SUPPL. 22},
pmid = {18551414},
title = {{Using ZINC to acquire a virtual screening library}},
year = {2008}
}
@article{Jungfleisch2015,
abstract = {The Lsm1-7-Pat1 complex binds to the 3' end of cellular mRNAs and promotes 3' end protection and 5'-3' decay. Interestingly, this complex also specifically binds to cis-acting regulatory sequences of viral positive-strand RNA genomes promoting their translation and subsequent recruitment from translation to replication. Yet, how the Lsm1-7-Pat1 complex regulates these two processes remains elusive. Here, we show that Lsm1-7-Pat1 complex acts differentially in these processes. By using a collection of well-characterized lsm1 mutant alleles and a system that allows the replication of Brome mosaic virus (BMV) in yeast we show that the Lsm1-7-Pat1 complex integrity is essential for both, translation and recruitment. However, the intrinsic RNA-binding ability of the complex is only required for translation. Consistent with an RNA-binding-independent function of the Lsm1-7-Pat1 complex on BMV RNA recruitment, we show that the BMV 1a protein, the sole viral protein required for recruitment, interacts with this complex in an RNA-independent manner. Together, these results support a model wherein Lsm1-7-Pat1 complex binds consecutively to BMV RNA regulatory sequences and the 1a protein to promote viral RNA translation and later recruitment out of the host translation machinery to the viral replication complexes.},
author = {Jungfleisch, Jennifer and Chowdhury, Ashis and Alves-Rodrigues, Isabel and Tharun, Sundaresan and Diez, Juana},
doi = {10.1261/rna.052209.115},
issn = {1469-9001 (Electronic)},
journal = {RNA (New York, N.Y.)},
keywords = {bmv,decapping activators,lsm proteins,lsm1-7,lsm1-7-pat1 complex,pat1,replication,rna virus,translation,viral rna},
number = {8},
pages = {1469--1479},
pmid = {26092942},
title = {{The Lsm1-7-Pat1 complex promotes viral RNA translation and replication by differential mechanisms.}},
volume = {21},
year = {2015}
}
@misc{Mildvan2005,
abstract = {Nudix hydrolases catalyze the hydrolysis of nucleoside diphosphates linked to other moieties, X, and contain the sequence motif or Nudix box, GX5EX7REUXEEXGU. The mechanisms of Nudix hydrolases are highly diverse in the position on the substrate at which nucleophilic substitution occurs, and in the number of required divalent cations. While most proceed by associative nucleophilic substitutions by water at specific internal phosphorus atoms of a diphosphate or polyphosphate chain, members of the GDP-mannose hydrolase sub-family catalyze dissociative nucleophilic substitutions, by water, at carbon. The site of substitution is likely determined by the positions of the general base and the entering water. The rate accelerations or catalytic powers of Nudix hydrolases range from 109- to 1012-fold. The reactions are accelerated 103-105-fold by general base catalysis by a glutamate residue within, or beyond the Nudix box, or by a histidine beyond the Nudix box. Lewis acid catalysis, which contributes ≥103-105-fold to the rate acceleration, is provided by one, two, or three divalent cations. One divalent cation is coordinated by two or three conserved residues of the Nudix box, the initial glycine and one or two glutamate residues, together with a remote glutamate or glutamine ligand from beyond the Nudix box. Some Nudix enzymes require one (MutT) or two additional divalent cations (Ap4AP), to neutralize the charge of the polyphosphate chain, to help orient the attacking hydroxide or oxide nucleophile, and/or to facilitate the departure of the anionic leaving group. Additional catalysis (10-103-fold) is provided by the cationic side chains of lysine and arginine residues and by H-bond donation by tyrosine residues, to orient the general base, or to promote the departure of the leaving group. The overall rate accelerations can be explained by both independent and cooperative effects of these catalytic components. {\textcopyright} 2004 Elsevier Inc. All rights reserved.},
author = {Mildvan, A. S. and Xia, Z. and Azurmendi, H. F. and Saraswat, V. and Legler, P. M. and Massiah, M. A. and Gabelli, S. B. and Bianchet, M. A. and Kang, L. W. and Amzel, L. M.},
booktitle = {Archives of Biochemistry and Biophysics},
doi = {10.1016/j.abb.2004.08.017},
isbn = {0003-9861 (Print)$\backslash$r0003-9861 (Linking)},
issn = {00039861},
keywords = {Catalytic power,Divalent cation activators,General base catalysis,Lewis acid catalysis,Mutagenesis studies,NMR,Nudix enzymes,Nudix sequence motif,Pulsed EPR,Solution structures,X-ray structures},
number = {1},
pages = {129--143},
pmid = {15581572},
title = {{Structures and mechanisms of Nudix hydrolases}},
volume = {433},
year = {2005}
}
@article{Ameen-Ali2015,
abstract = {This review will consider how spontaneous tasks have been applied alongside neuroscientific techniques to test complex forms of recognition memory for objects and their environmental features, e.g. the spatial location of an object or the context in which it is presented. We discuss studies that investigate the roles of the perirhinal cortex and the hippocampus in recognition memory using standard testing paradigms, and consider how these findings contribute to the ongoing debate about whether recognition memory is a single unitary process or multiple processes that can be dissociated anatomically and functionally. Due to the wide use of spontaneous tasks, the need for improved procedures that reduce animal use is acknowledged, with multiple trial paradigms discussed as a novel way of reducing variability and animal numbers in these tasks. The importance of improving translation of animal models to humans is highlighted, with emphasis on a shift away from relying on the phenomenological experience of human subjects.},
author = {Ameen-Ali, K. E. and Easton, A. and Eacott, M. J.},
doi = {10.1016/j.neubiorev.2015.03.013},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Ameen-Ali, Easton, Eacott - 2015 - Moving beyond standard procedures to assess spontaneous recognition memory.pdf:pdf},
isbn = {1873-7528 (Electronic)$\backslash$r0149-7634 (Linking)},
issn = {18737528},
journal = {Neuroscience and Biobehavioral Reviews},
keywords = {Episodic memory,Familiarity,Hippocampus,Novelty,Perirhinal cortex,Recognition memory},
pages = {37--51},
pmid = {25842032},
publisher = {Elsevier Ltd},
title = {{Moving beyond standard procedures to assess spontaneous recognition memory}},
url = {http://dx.doi.org/10.1016/j.neubiorev.2015.03.013},
volume = {53},
year = {2015}
}
@article{Shmulevich2002,
abstract = {Motivation: Our goal is to construct a model for genetic regulatory networks such that the model class: (i) incorporates rule-based dependencies between genes; (ii) allows the systematic study of global network dynamics; (iii) is able to cope with uncertainty, both in the data and the model selection; and (iv) permits the quantification of the relative influence and sensitivity of genes in their interactions with other genes. Results: We introduce Probabilistic Boolean Networks (PBN) that share the appealing rule-based properties of Boolean networks, but are robust in the face of uncertainty. We show how the dynamics of these networks can be studied in the probabilistic context of Markov chains, with standard Boolean networks being special cases. Then, we discuss the relationship between PBNs and Bayesian networks-a family of graphical models that explicitly represent probabilistic relationships between variables. We show how probabilistic dependencies between a gene and its parent genes, constituting the basic building blocks of Bayesian networks, can be obtained from PBNs. Finally, we present methods for quantifying the influence of genes on other genes, within the context of PBNs. Examples illustrating the above concepts are presented throughout the paper.},
author = {Shmulevich, I. and Dougherty, E. R. and Kim, S. and Zhang, W.},
doi = {10.1093/bioinformatics/18.2.261},
file = {:Users/ozlem/Desktop/papers/BooleanModel.pdf:pdf},
isbn = {1367-4803},
issn = {1367-4803},
journal = {Bioinformatics},
pmid = {11847074},
title = {{Probabilistic Boolean networks: a rule-based uncertainty model for gene regulatory networks}},
year = {2002}
}
@article{Liang2015,
abstract = {Genome editing tools such as the clustered regularly interspaced short palindromic repeat (CRISPR)-associated system (Cas) have been widely used to modify genes in model systems including animal zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISPR/Cas9 in human pre-implantation embryos. In this report, we used tripronuclear (3PN) zygotes to further investigate CRISPR/Cas9-mediated gene editing in human cells. We found that CRISPR/Cas9 could effectively cleave the endogenous $\beta$-globin gene (HBB). However, the efficiency of homologous recombination directed repair (HDR) of HBB was low and the edited embryos were mosaic. Off-target cleavage was also apparent in these 3PN zygotes as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene (HBD), which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBB locus in these embryos occurred preferentially through the non-crossover HDR pathway. Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any clinical applications of CRSIPR/Cas9-mediated editing.},
archivePrefix = {arXiv},
arxivId = {38},
author = {Liang, Puping and Xu, Yanwen and Zhang, Xiya and Ding, Chenhui and Huang, Rui and Zhang, Zhen and Lv, Jie and Xie, Xiaowei and Chen, Yuxi and Li, Yujing and Sun, Ying and Bai, Yaofu and Songyang, Zhou and Ma, Wenbin and Zhou, Canquan and Huang, Junjiu},
doi = {10.1007/s13238-015-0153-5},
eprint = {38},
isbn = {1674-8018 (Electronic)$\backslash$r1674-800X (Linking)},
issn = {16748018},
journal = {Protein and Cell},
keywords = {CRISPR/Cas9,gene editing,homologous recombination,human tripronuclear zygotes,whole-exome sequencing,$\beta$-thalassemia},
number = {5},
pages = {363--372},
pmid = {25894090},
title = {{CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes}},
volume = {6},
year = {2015}
}
@article{Albert2004,
abstract = {. Biological systems form complex networks of interaction on several scales, ranging from the molecular to the ecosystem level. On the subcellular scale, interaction between genes and gene products (mRNAs, proteins) forms the basis of essential processes like signal transduction, cell metabolism or embryonic development. Recent experimental advances helped uncover the qualitative structure of many gene control networks, creating a surge of interest in the quantitative description of gene regulation. We give a brief description of the main frameworks and methods used in modeling gene regulatory networks, then focus on a recent model of the segment polarity genes of the fruit fly Drosophila melanogaster. The basis of this model is the known interactions between the products of the segment polarity genes, and the network topology these interactions form. The interactions between mRNAs and proteins are described as logical (Boolean) functions. The success in reproducing both wild type and mutant gene expression patterns suggests that the kinetic details of the interactions are not essential as long as the network of interactions is unperturbed. The model predicts the gene patterns for cases that were not yet studied experimentally, and implies a remarkable robustness toward changes in internal parameters, initial conditions and even some mutations. The success of this approach also suggests a wide applicability of real-topologybased Boolean modeling for gene regulatory networks. In cases when the information about the system is incomplete, Boolean modeling can verify the sufficiency of interactions and can propose ways to complete the network. After a coherent picture is obtained, more realistic kinetic models can be used to gain additional insights into the functioning of the system.},
author = {Albert, R{\'{e}}ka},
doi = {10.1007/978-3-540-44485-5_21},
issn = {978-3-540-22354-2},
journal = {Gene},
title = {{Boolean Modeling of Genetic Regulatory Networks}},
year = {2004}
}
@article{Mollapour2007,
abstract = {Aquaporins and aquaglyceroporins form the membrane channels that mediate fluxes of water and small solute molecules into and out of cells. Eukaryotes often use mitogen-activated protein kinase (MAPK) cascades for the intracellular signaling of stress. This study reveals an aquaglyceroporin being destabilized by direct MAPK phosphorylation and also a stress resistance being acquired through this channel loss. Hog1 MAPK is transiently activated in yeast exposed to high, toxic levels of acetic acid. This Hog1 then phosphorylates the plasma membrane aquaglyceroporin, Fps1, a phosphorylation that results in Fps1 becoming ubiquitinated and endocytosed and then degraded in the vacuole. As Fps1 is the membrane channel that facilitates passive diffusional flux of undissociated acetic acid into the cell, this loss downregulates such influx in low-pH cultures, where acetic acid (pKa, 4.75) is substantially undissociated. Consistent with this downregulation of the acid entry generating resistance, sensitivity to acetic acid is seen with diverse mutational defects that abolish endocytic removal of Fps1 from the plasma membrane (loss of Hog1, loss of the soluble domains of Fps1, a T231A S537A double mutation of Fps1 that prevents its in vivo phosphorylation, or mutations generating a general loss of endocytosis of cell surface proteins [doa4Delta and end3Delta]). Remarkably, targetting of Fps1 for degradation may be the major requirement for an active Hog1 in acetic acid resistance, since Hog1 is largely dispensable for such resistance when the cells lack Fps1. Evidence is presented that in unstressed cells, Hog1 exists in physical association with the N-terminal cytosolic domain of Fps1.},
author = {Mollapour, M. and Piper, P. W.},
doi = {10.1128/MCB.02205-06},
isbn = {0270-7306},
issn = {0270-7306},
journal = {Molecular and Cellular Biology},
number = {18},
pages = {6446--6456},
pmid = {17620418},
title = {{Hog1 Mitogen-Activated Protein Kinase Phosphorylation Targets the Yeast Fps1 Aquaglyceroporin for Endocytosis, Thereby Rendering Cells Resistant to Acetic Acid}},
url = {http://mcb.asm.org/cgi/doi/10.1128/MCB.02205-06},
volume = {27},
year = {2007}
}
@misc{Nevoigt1997,
abstract = {Glycerol is the main compatible solute in Saccharomyces cerevisiae. It is accumulated intracellularly when cells are exposed to decreased extracellular water activity. In general, increased intracellular accumulation of a solute may be caused by enhanced production, restricted dissimilation, increased retention by the plasma membrane and increased uptake from the medium. In this review, we evaluate current knowledge concerning mechanisms leading to the accumulation of glycerol in osmotically stressed cells of S. cerevisiae at the molecular and metabolic levels. An overview of glycerol metabolism in S. cerevisiae is provided.},
author = {Nevoigt, Elke and Stahl, Ulf},
booktitle = {FEMS Microbiology Reviews},
doi = {10.1016/S0168-6445(97)00058-2},
isbn = {0168-6445 (Print)$\backslash$r0168-6445 (Linking)},
issn = {01686445},
keywords = {Glycerol metabolism,Osmoregulation,Saccharomyces cerevisiae,Yeast},
number = {3},
pages = {231--241},
pmid = {9451815},
title = {{Osmoregulation and glycerol metabolism in the yeast Saccharomyces cerevisiae}},
volume = {21},
year = {1997}
}
@article{Morris2013,
abstract = {Mathematical models are useful tools for understanding protein signaling networks because they provide an integrated view of pharmacological and toxicological processes at the molecular level. Here we describe an approach previously introduced based on logic modeling to generate cell-specific, mechanistic and predictive models of signal transduction. Models are derived from a network encoding prior knowledge that is trained to signaling data, and can be either binary (based on Boolean logic) or quantitative (using a recently developed formalism, constrained fuzzy logic). The approach is implemented in the freely available tool CellNetOptimizer (CellNOpt). We explain the process CellNOpt uses to train a prior knowledge network to data and illustrate its application with a toy example as well as a realistic case describing signaling networks in the HepG2 liver cancer cell line.},
author = {Morris, Melody K. and Melas, Ioannis and Saez-Rodriguez, Julio},
doi = {10.1007/978-1-62703-059-5_8},
isbn = {9781627030588},
issn = {10643745},
journal = {Methods in Molecular Biology},
keywords = {Boolean logic,Cell-specificity,Fuzzy logic,Logic model,Protein networks,Signal transduction},
pmid = {23086842},
title = {{Construction of cell type-specific logic models of signaling networks using CellNOpt}},
year = {2013}
}
@article{Guirouilh-Barbat2004,
abstract = {Using a substrate measuring deletion or inversion of an I-SceI-excised fragment and both accurate and inaccurate rejoining, we determined the impact of non-homologous end-joining (NHEJ) on mammalian chromosome rearrangements. Deletion is 2- to 8-fold more efficient than inversion, independent of the DNA ends structure. KU80 controls accurate rejoining, whereas in absence of KU mutagenic rejoining, particularly microhomology-mediated repair, occurs efficiently. In cells bearing both the NHEJ and a homologous recombination (HR) substrate containing a third I-SceI site, we show that NHEJ is at least 3.3-fold more efficient than HR, and translocation of the I-SceI fragment from the NHEJ substrate locus into the HR-I-SceI site can occur, but 50- to 100-fold less frequently than deletion. Deletions and translocations show both accurate and inaccurate rejoining, suggesting that they correspond to a mix of KU-dependent and KU-independent processes. Thus these processes should represent prominent pathways for DSB-induced genetic instability in mammalian cells.},
author = {Guirouilh-Barbat, Jos{\'{e}}e and Huck, Sylvie and Bertrand, Pascale and Pirzio, Livia and Desmaze, Chantal and Sabatier, Laure and Lopez, Bernard S.},
doi = {10.1016/j.molcel.2004.05.008},
isbn = {1097-2765},
issn = {10972765},
journal = {Molecular Cell},
number = {5},
pages = {611--623},
pmid = {15175156},
title = {{Impact of the KU80 pathway on NHEJ-induced genome rearrangements in mammalian cells}},
volume = {14},
year = {2004}
}
@article{Jhanwar-Uniyal2015,
abstract = {Mechanistic target of rapamycin (mTOR) is a serine–threonine kinase that functions via two multiprotein complexes, namely mTORC1 and mTORC2, each characterized by different binding partners that confer separate functions. mTORC1 function is tightly regulated by PI3-K/Akt and is sensitive to rapamycin. mTORC2 is sensitive to growth factors, not nutrients, and is associated with rapamycin-insensitivity. mTORC1 regulates protein synthesis and cell growth through downstream molecules: 4E-BP1 (also called EIF4E-BP1) and S6K. Also, mTORC2 is thought to modulate growth factor signaling by phosphorylating the C-terminal hydrophobic motif of some AGC kinases such as Akt and SGK. Recent evidence has suggested that mTORC2 may play an important role in maintenance of normal as well as cancer cells by virtue of its association with ribosomes, which may be involved in metabolic regulation of the cell. Rapamycin (sirolimus) and its analogs known as rapalogues, such as RAD001 (everolimus) and CCI-779 (temsirolimus), suppress mTOR activity through an allosteric mechanism that acts at a distance from the ATP-catalytic binding site, and are considered incomplete inhibitors. Moreover, these compounds suppress mTORC1-mediated S6K activation, thereby blocking a negative feedback loop, leading to activation of mitogenic pathways promoting cell survival and growth. Consequently, mTOR is a suitable target of therapy in cancer treatments. However, neither of these complexes is fully inhibited by the allosteric inhibitor rapamycin or its analogs. In recent years, new pharmacologic agents have been developed which can inhibit these complexes via ATP-binding mechanism, or dual inhibition of the canonical PI3-K/Akt/mTOR signaling pathway. These compounds include WYE-354, KU-003679, PI-103, Torin1, and Torin2, which can target both complexes or serve as a dual inhibitor for PI3-K/mTOR. This investigation describes the mechanism of action of pharmacological agents that effectively target mTORC1 and mTORC2 resulting in suppression of growth, proliferation, and migration of tumor and cancer stem cells.},
author = {Jhanwar-Uniyal, Meena and Gillick, John L. and Neil, Jayson and Tobias, Michael and Thwing, Zachary E. and Murali, Raj},
doi = {10.1016/J.JBIOR.2014.09.004},
issn = {2212-4926},
journal = {Advances in Biological Regulation},
month = {jan},
pages = {64--74},
publisher = {Pergamon},
title = {{Distinct signaling mechanisms of mTORC1 and mTORC2 in glioblastoma multiforme: A tale of two complexes}},
url = {https://www.sciencedirect.com/science/article/pii/S2212492614000438?via{\%}3Dihub},
volume = {57},
year = {2015}
}
@article{Okano2000,
abstract = {Overexpression of epidermal growth factor receptor (EGFR) in certain cancers is well established. There is growing evidence that epidermal growth factor (EGF) activates Akt/protein kinase B (PKB) in a phosphoinositide 3-OH kinase (PI3K)-dependent manner, but it is not yet clear which Akt isoforms are involved in this signal transduction pathway. We investigated the functional regulation of three Akt isoforms, Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma, in esophageal cancer cells where EGFR is frequently overexpressed. Upon EGF simulation, phosphorylation of Akt1 at the Ser-473 residue was remarkably induced. This result was corroborated by in vitro Akt kinase assays using glycogen synthase kinase 3beta as the substrate. PI3K inhibitors, wortmannin or LY294002, significantly blocked the Akt kinase activity induced by EGF. Akt2 activity was evaluated by electrophoretic mobility shift assays. Robust activation of Akt2 by EGF was observed in some cell lines in a PI3K-dependent manner. EGF-induced Akt3 activation was demonstrated by Ser-472 phosphorylation of Akt3 but in a restrictive fashion. In aggregate, EGF-mediated activation of Akt isoforms is overlapping and distinctive. The mechanism by which EGFR recruits the PI3K/Akt pathway was in part differentially regulated at the level of Ras but independent of heterodimerization of EGFR with either ErbB2 or ErbB3 based upon functional dissection of pathways in esophageal cancer cell lines.},
author = {Okano, Jun Ichi and Gaslightwala, Irphan and Birnbaum, Morris J. and Rustgi, Anil K. and Nakagawa, Hiroshi},
doi = {10.1074/jbc.M004112200},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/J. Biol. Chem.-2000-Okano-30934-42.pdf:pdf},
isbn = {0021-9258 (Print)$\backslash$r0021-9258 (Linking)},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {10908564},
title = {{Akt/protein kinase B isoforms are differentially regulated by epidermal growth factor stimulation}},
year = {2000}
}
@article{Inoki2002,
abstract = {Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by the formation of hamartomas in a wide range of human tissues. Mutation in either the TSC1 or TSC2 tumour suppressor gene is responsible for both the familial and sporadic forms of this disease. TSC1 and TSC2 proteins form a physical and functional complex in vivo. Here, we show that TSC1-TSC2 inhibits the p70 ribosomal protein S6 kinase 1 (an activator of translation) and activates the eukaryotic initiation factor 4E binding protein 1 (4E-BP1, an inhibitor of translational initiation). These functions of TSC1-TSC2 are mediated by inhibition of the mammalian target of rapamycin (mTOR). Furthermore, TSC2 is directly phosphorylated by Akt, which is involved in stimulating cell growth and is activated by growth stimulating signals, such as insulin. TSC2 is inactivated by Akt-dependent phosphorylation, which destabilizes TSC2 and disrupts its interaction with TSC1. Our data indicate a molecular mechanism for TSC2 in insulin signalling, tumour suppressor functions and in the inhibition of cell growth.},
archivePrefix = {arXiv},
arxivId = {arXiv:gr-qc/9809069v1},
author = {Inoki, Ken and Li, Yong and Zhu, Tianquan and Wu, Jun and Guan, Kun Liang},
doi = {10.1038/ncb839},
eprint = {9809069v1},
isbn = {1465-7392 (Print)$\backslash$r1465-7392 (Linking)},
issn = {14657392},
journal = {Nature Cell Biology},
pmid = {12172553},
primaryClass = {arXiv:gr-qc},
title = {{TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling}},
year = {2002}
}
@article{Kuperstein2015,
abstract = {Cancerogenesis is driven by mutations leading to aberrant functioning of a complex network of molecular interactions and simultaneously affecting multiple cellular functions. Therefore, the successful application of bioinformatics and systems biology methods for analysis of high-throughput data in cancer research heavily depends on availability of global and detailed reconstructions of signalling networks amenable for computational analysis. We present here the Atlas of Cancer Signalling Network (ACSN), an interactive and comprehensive map of molecular mechanisms implicated in cancer. The resource includes tools for map navigation, visualization and analysis of molecular data in the context of signalling network maps. Constructing and updating ACSN involves careful manual curation of molecular biology literature and participation of experts in the corresponding fields. The cancer-oriented content of ACSN is completely original and covers major mechanisms involved in cancer progression, including DNA repair, cell survival, apoptosis, cell cycle, EMT and cell motility. Cell signalling mechanisms are depicted in detail, together creating a seamless 'geographic-like' map of molecular interactions frequently deregulated in cancer. The map is browsable using NaviCell web interface using the Google Maps engine and semantic zooming principle. The associated web-blog provides a forum for commenting and curating the ACSN content. ACSN allows uploading heterogeneous omics data from users on top of the maps for visualization and performing functional analyses. We suggest several scenarios for ACSN application in cancer research, particularly for visualizing high-throughput data, starting from small interfering RNA-based screening results or mutation frequencies to innovative ways of exploring transcriptomes and phosphoproteomes. Integration and analysis of these data in the context of ACSN may help interpret their biological significance and formulate mechanistic hypotheses. ACSN may also support patient stratification, prediction of treatment response and resistance to cancer drugs, as well as design of novel treatment strategies.},
author = {Kuperstein, I. and Bonnet, E. and Nguyen, H. A. and Cohen, D. and Viara, E. and Grieco, L. and Fourquet, S. and Calzone, L. and Russo, C. and Kondratova, M. and Dutreix, M. and Barillot, E. and Zinovyev, A.},
doi = {10.1038/oncsis.2015.19},
file = {:Users/ozlem/Desktop/papers/Kuperstein2015.pdf:pdf},
isbn = {21579024 (Electronic)},
issn = {21579024},
journal = {Oncogenesis},
number = {7},
pages = {e160--14},
pmid = {26192618},
publisher = {Nature Publishing Group},
title = {{Atlas of Cancer Signalling Network: A systems biology resource for integrative analysis of cancer data with Google Maps}},
volume = {4},
year = {2015}
}
@article{Prudent2005a,
abstract = {Osmoregulation plays an important role in cellular responses to osmotic stress in plants and in yeast. Aquaporins contribute to osmotic adjustment by facilitating transport of water or solutes across membranes. The tonoplastic water channel BobTIP1;1 (original name BobTIP26-1) genes are upregulated during dessication stress in cauliflower meristematic tissue. To investigate the physiological importance of BobTIP1;1, we expressed it in a Saccharomyces cerevisiae osmosensitive mutant fps1$\Delta$. We showed that the defect in the yeast glycerol plasma membrane transporter is complemented by a plant cDNA encoding the aquaporin BobTIP1;1 which is localized in the vacuolar membrane of the complemented yeast cells. To our knowledge, this is the first example of a plant aquaporin for which localization in the vacuolar membrane of yeast cells is related to an osmoresistant phenotype under hypo-osmotic shock. {\textcopyright} 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.},
author = {Prudent, S{\'{e}}bastien and Marty, Francis and Charbonnier, Maryse},
doi = {10.1016/j.febslet.2005.05.076},
isbn = {0014-5793 (Print)$\backslash$r0014-5793 (Linking)},
issn = {00145793},
journal = {FEBS Letters},
keywords = {Aquaporin,Hypo-osmotic shock,Osmotic stress,Vacuolar membrane,$\gamma$-TIP},
number = {18},
pages = {3872--3880},
pmid = {16004998},
title = {{The yeast osmosensitive mutant fps1$\Delta$ transformed by the cauliflower BobTIP1;1 aquaporin withstand a hypo-osmotic shock}},
volume = {579},
year = {2005}
}
@article{Tharun2000,
abstract = {One of the main mechanisms of messenger RNA degradation in eukaryotes occurs by deadenylation-dependent decapping which leads to 5'-to-3' decay. A family of Sm-like (Lsm) proteins has been identified, members of which contain the 'Sm' sequence motif, form a complex with U6 small nuclear RNA and are required for pre-mRNA splicing. Here we show that mutations in seven yeast Lsm proteins (Lsm1-Lsm7) also lead to inhibition of mRNA decapping. In addition, the Lsm1-Lsm7 proteins co-immunoprecipitate with the mRNA decapping enzyme (Dcp1), a decapping activator (Pat1/Mrt1) and with mRNA. This indicates that the Lsm proteins may promote decapping by interactions with the mRNA and the decapping machinery. In addition, the Lsm complex that functions in mRNA decay appears to be distinct from the U6-associated Lsm complex, indicating that Lsm proteins form specific complexes that affect different aspects of mRNA metabolism.},
author = {Tharun, Sundaresan and He, Welhal and Mayes, Andrew E. and Lennertz, Pascal and Beggs, Jean D. and Parker, Roy},
doi = {10.1038/35006676},
isbn = {0028-0836 (Print)$\backslash$n0028-0836 (Linking)},
issn = {00280836},
journal = {Nature},
number = {6777},
pages = {515--518},
pmid = {10761922},
title = {{Yeast Sm-like proteins function in mRNA decapping and decay}},
volume = {404},
year = {2000}
}
@article{Becerra2002,
abstract = {The transcriptome of Saccharomyces cerevisiae was screened using the high-density membrane hybridization method, under aerobic and hypoxic conditions, in wild-type and mutant backgrounds obtained by the disruption of the genes encoding the regulatory proteins Hap1, Rox1 and the Srb10 and Rox3 subunits of RNA polymerase II holoenzyme. None of the mutations studied was able to fully overcome the wild-type hypoxic response. Deletion of the hap1 gene changed the expression profiles of individual open reading frames (ORFs) under both aerobic and hypoxic conditions. Major changes associated with rox3 deletion were related to the hypoxic activation. Rox3 also caused a repressor effect (oxygen-independent) on a subset of genes related to subtelomeric proteins. With regard to the effect brought about by the deletion of rox1 and srb10, correspondence cluster analysis revealed that the transcriptome profile in aerobic conditions is very similar in the wild-type and both deletion strains. In contrast, however, differences were found during hypoxia between the subgroup formed by wild-type and the Drox1 deletant compared with the Dsrb10 deletant. An analysis of selected ORFs responding to hypoxia, in association with a dependence on the regulatory factors studied, made it possible to iden- tify the clusters that are related to different regulatory circuits},
author = {Becerra, Manuel and Lombard{\'{i}}a-Ferreira, Luis J. and Hauser, Nicole C. and Hoheisel, J{\"{o}}rg D. and Tizon, Bel{\'{e}}n and Cerd{\'{a}}n, M. Esperanza},
doi = {10.1046/j.1365-2958.2002.02724.x},
isbn = {0950-382X (Print)$\backslash$n0950-382X (Linking)},
issn = {0950382X},
journal = {Molecular Microbiology},
number = {3},
pages = {545--555},
pmid = {11929514},
title = {{The yeast transcriptome in aerobic and hypoxic conditions: Effects of hap1, rox1, rox3 and srb10 deletions}},
volume = {43},
year = {2002}
}
@article{Stoll2012,
abstract = {UNLABELLED: Mathematical modeling is used as a Systems Biology tool to answer biological questions, and more precisely, to validate a network that describes biological observations and predict the effect of perturbations. This article presents an algorithm for modeling biological networks in a discrete framework with continuous time.$\backslash$n$\backslash$nBACKGROUND: There exist two major types of mathematical modeling approaches: (1) quantitative modeling, representing various chemical species concentrations by real numbers, mainly based on differential equations and chemical kinetics formalism; (2) and qualitative modeling, representing chemical species concentrations or activities by a finite set of discrete values. Both approaches answer particular (and often different) biological questions. Qualitative modeling approach permits a simple and less detailed description of the biological systems, efficiently describes stable state identification but remains inconvenient in describing the transient kinetics leading to these states. In this context, time is represented by discrete steps. Quantitative modeling, on the other hand, can describe more accurately the dynamical behavior of biological processes as it follows the evolution of concentration or activities of chemical species as a function of time, but requires an important amount of information on the parameters difficult to find in the literature.$\backslash$n$\backslash$nRESULTS: Here, we propose a modeling framework based on a qualitative approach that is intrinsically continuous in time. The algorithm presented in this article fills the gap between qualitative and quantitative modeling. It is based on continuous time Markov process applied on a Boolean state space. In order to describe the temporal evolution of the biological process we wish to model, we explicitly specify the transition rates for each node. For that purpose, we built a language that can be seen as a generalization of Boolean equations. Mathematically, this approach can be translated in a set of ordinary differential equations on probability distributions. We developed a C++ software, MaBoSS, that is able to simulate such a system by applying Kinetic Monte-Carlo (or Gillespie algorithm) on the Boolean state space. This software, parallelized and optimized, computes the temporal evolution of probability distributions and estimates stationary distributions.$\backslash$n$\backslash$nCONCLUSIONS: Applications of the Boolean Kinetic Monte-Carlo are demonstrated for three qualitative models: a toy model, a published model of p53/Mdm2 interaction and a published model of the mammalian cell cycle. Our approach allows to describe kinetic phenomena which were difficult to handle in the original models. In particular, transient effects are represented by time dependent probability distributions, interpretable in terms of cell populations.},
archivePrefix = {arXiv},
arxivId = {1204.0997},
author = {Stoll, Gautier and Viara, Eric and Barillot, Emmanuel and Calzone, Laurence},
doi = {10.1186/1752-0509-6-116},
eprint = {1204.0997},
file = {:Users/ozlem/Desktop/Tools/1752-0509-6-116.pdf:pdf},
issn = {17520509},
journal = {BMC Systems Biology},
keywords = {Boolean modeling,Continuous time,Gillespie algorithm,Markov process},
pages = {1--18},
pmid = {22932419},
title = {{Continuous time boolean modeling for biological signaling: application of Gillespie algorithm}},
volume = {6},
year = {2012}
}
@article{LaLonde2013,
abstract = {The design, synthesis, thermodynamic and crystallographic characterization of a potent, broad spectrum, second-generation HIV-1 entry inhibitor that engages conserved carbonyl hydrogen bonds within gp120 has been achieved. The optimized antagonist exhibits a sub-micromolar binding affinity (110 nM) and inhibits viral entry of clade B and C viruses (IC50 geometric mean titer of 1.7 and 14.0 $\mu$M, respectively), without promoting CD4-independent viral entry. thermodynamic signatures indicate a binding preference for the (R,R)-over the (S,S)-enantiomer. The crystal structure of the small molecule-gp120 complex reveals the displacement of crystallographic water and the formation of a hydrogen bond with a backbone carbonyl of the bridging sheet. Thus, structure-based design and synthesis targeting the highly conserved and structurally characterized CD4:gp120 interface is an effective tactic to enhance the neutralization potency of small molecule HIV-1 entry inhibitors.},
author = {LaLonde, Judith M. and Le-Khac, Matthew and Jones, David M. and Courter, Joel R. and Park, Jongwoo and Sch{\"{o}}n, Arne and Princiotto, Amy M. and Wu, Xueling and Mascola, John R. and Freire, Ernesto and Sodroski, Joseph and Madani, Navid and Hendrickson, Wayne A. and Smith, Amos B.},
doi = {10.1021/ml300407y},
issn = {19485875},
journal = {ACS Medicinal Chemistry Letters},
keywords = {CD4,HIV,X-ray crystallography,entry inhibitor,gp120,protein-protein interactions,structure-based drug design,thermodynamics,viral inhibition},
number = {3},
pages = {338--343},
pmid = {23667716},
title = {{Structure-based design and synthesis of an HIV-1 entry inhibitor exploiting X-ray and thermodynamic characterization}},
volume = {4},
year = {2013}
}
@article{Sharma2005,
abstract = {DNA helicases have essential roles in nucleic acid metabolism by facilitating cellular processes including replication, recombination, DNA repair, and transcription. The vital roles of helicases in these pathways are reflected by their emerging importance in the maintenance of genomic stability. Recently, a number of human diseases with cancer predisposition have been shown to be genetically linked to a specific helicase defect. This has led researchers to further investigate the roles of helicases in cancer biology, and to study the efficacy of targeting human DNA helicases for anti-cancer drug treatment. Helicase-specific inhibition in malignant cells may compromise the high proliferation rates of cancerous tissues. The role of RecQ helicases in response to replicational stress suggests a molecular target for selectively eliminating malignant tumor cells by a cancer chemotherapeutic agent. Alternate DNA secondary structures such as G-quadruplexes that may form in regulatory regions of oncogenes or G-rich telomere sequences are potential targets for cancer therapy since these sequence-specific structures are proposed to affect gene expression and telomerase activation, respectively. Small molecule inhibitors of G-quadruplex helicases may be used to regulate cell cycle progression by modulating promotor activation or disrupting telomere maintenance, important processes of cellular transformation. The design of small molecules which deter helicase function at telomeres may provide a molecular target since telomerase activity is necessary for the proliferation of numerous immortal cells. Although evidence suggests that helicases are specifically inhibited by certain DNA binding compounds, another area of promise in anti-cancer therapy is siRNA technology. Specific knockdown of helicase expression can be utilized as a means to sensitize oncogenic proliferating cell lines. This review will address these topics in detail and summarize the current avenues of research in anti-cancer therapy targeting helicases through small molecule inhibitors of DNA-protein complexes, DNA binding drugs, or down-regulation of helicase gene expression.},
author = {Sharma, Sudha and Doherty, Kevin M and Brosh, Robert M},
doi = {10.2174/1568011053765985},
isbn = {1568-0118 (Print)},
issn = {1568-0118},
journal = {Current medicinal chemistry. Anti-cancer agents},
keywords = {Animals,Antineoplastic Agents,Antineoplastic Agents: chemistry,Antineoplastic Agents: metabolism,Antineoplastic Agents: pharmacology,Cell Proliferation,Cell Proliferation: drug effects,DNA,DNA Helicases,DNA Helicases: antagonists {\&} inhibitors,DNA Helicases: genetics,DNA Repair,DNA Replication,DNA Replication: drug effects,DNA: chemistry,DNA: metabolism,Enzyme Inhibitors,Enzyme Inhibitors: chemistry,Enzyme Inhibitors: metabolism,Enzyme Inhibitors: pharmacology,G-Quadruplexes,Humans,Nucleic Acid Conformation,Substrate Specificity},
number = {3},
pages = {183--99},
pmid = {15992349},
title = {{DNA helicases as targets for anti-cancer drugs.}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/15992349},
volume = {5},
year = {2005}
}
@article{Margolin2006,
abstract = {Background: Elucidating gene regulatory networks is crucial for understanding normal cell physiology and complex pathologic phenotypes. Existing computational methods for the genome-wide "reverse engineering" of such networks have been successful only for lower eukaryotes with simple genomes. Here we present ARACNE, a novel algorithm, using microarray expression profiles, specifically designed to scale up to the complexity of regulatory networks in mammalian cells, yet general enough to address a wider range of network deconvolution problems. This method uses an information theoretic approach to eliminate the majority of indirect interactions inferred by co-expression methods. Results: We prove that ARACNE reconstructs the network exactly (asymptotically) if the effect of loops in the network topology is negligible, and we show that the algorithm works well in practice, even in the presence of numerous loops and complex topologies. We assess ARACNE's ability to reconstruct transcriptional regulatory networks using both a realistic synthetic dataset and a microarray dataset from human B cells. On synthetic datasets ARACNE achieves very low error rates and outperforms established methods, such as Relevance Networks and Bayesian Networks. Application to the deconvolution of genetic networks in human B cells demonstrates ARACNE's ability to infer validated transcriptional targets of the cMYC proto-oncogene. We also study the effects of misestimation of mutual information on network reconstruction, and show that algorithms based on mutual information ranking are more resilient to estimation errors. Conclusion: ARACNE shows promise in identifying direct transcriptional interactions in mammalian cellular networks, a problem that has challenged existing reverse engineering algorithms. This approach should enhance our ability to use microarray data to elucidate functional mechanisms that underlie cellular processes and to identify molecular targets of pharmacological compounds in mammalian cellular networks.},
archivePrefix = {arXiv},
arxivId = {q-bio/0410037},
author = {Margolin, Adam A. and Nemenman, Ilya and Basso, Katia and Wiggins, Chris and Stolovitzky, Gustavo and Favera, Riccardo Dalla and Califano, Andrea},
doi = {10.1186/1471-2105-7-S1-S7},
eprint = {0410037},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Margolin et al. - 2006 - ARACNE An algorithm for the reconstruction of gene regulatory networks in a mammalian cellular context.pdf:pdf},
isbn = {1471-2105 (Electronic)},
issn = {14712105},
journal = {BMC Bioinformatics},
number = {SUPPL.1},
pages = {1--15},
pmid = {16723010},
primaryClass = {q-bio},
title = {{ARACNE: An algorithm for the reconstruction of gene regulatory networks in a mammalian cellular context}},
volume = {7},
year = {2006}
}
@article{Kanehisa2016b,
abstract = {KEGG (http://www.kegg.jp/ or http://www.genome.jp/ kegg/) is an integrated database resource for biolog-ical interpretation of genome sequences and other high-throughput data. Molecular functions of genes and proteins are associated with ortholog groups and stored in the KEGG Orthology (KO) database. The KEGG pathway maps, BRITE hierarchies and KEGG modules are developed as networks of KO nodes, representing high-level functions of the cell and the organism. Currently, more than 4000 com-plete genomes are annotated with KOs in the KEGG GENES database, which can be used as a refer-ence data set for KO assignment and subsequent reconstruction of KEGG pathways and other molec-ular networks. As an annotation resource, the fol-lowing improvements have been made. First, each KO record is re-examined and associated with pro-tein sequence data used in experiments of func-tional characterization. Second, the GENES database now includes viruses, plasmids, and the addendum category for functionally characterized proteins that are not represented in complete genomes. Third, new automatic annotation servers, BlastKOALA and GhostKOALA, are made available utilizing the non-redundant pangenome data set generated from the GENES database. As a resource for translational bioinformatics, various data sets are created for an-timicrobial resistance and drug interaction networks.},
author = {Kanehisa, Minoru and Sato, Yoko and Kawashima, Masayuki and Furumichi, Miho and Tanabe, Mao},
doi = {10.1093/nar/gkv1070},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Kanehisa et al. - 2016 - KEGG as a reference resource for gene and protein annotation(2).pdf:pdf},
isbn = {0305-1048},
issn = {13624962},
journal = {Nucleic Acids Research},
number = {D1},
pages = {D457--D462},
pmid = {26476454},
title = {{KEGG as a reference resource for gene and protein annotation}},
volume = {44},
year = {2016}
}
@article{Mali2013,
abstract = {Prokaryotic type II CRISPR-Cas systems can be adapted to enable targeted genome modifications across a range of eukaryotes. Here we engineer this system to enable RNA-guided genome regulation in human cells by tethering transcriptional activation domains either directly to a nuclease-null Cas9 protein or to an aptamer-modified single guide RNA (sgRNA). Using this functionality we developed a transcriptional activation-based assay to determine the landscape of off-target binding of sgRNA:Cas9 complexes and compared it with the off-target activity of transcription activator-like (TALs) effectors. Our results reveal that specificity profiles are sgRNA dependent, and that sgRNA:Cas9 complexes and 18-mer TAL effectors can potentially tolerate 1-3 and 1-2 target mismatches, respectively. By engineering a requirement for cooperativity through offset nicking for genome editing or through multiple synergistic sgRNAs for robust transcriptional activation, we suggest methods to mitigate off-target phenomena. Our results expand the versatility of the sgRNA:Cas9 tool and highlight the critical need to engineer improved specificity.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Mali, Prashant and Aach, John and Stranges, P Benjamin and Esvelt, Kevin M and Moosburner, Mark and Kosuri, Sriram and Yang, Luhan and Church, George M},
doi = {10.1038/nbt.2675},
eprint = {NIHMS150003},
isbn = {1546-1696 (Electronic)$\backslash$r1087-0156 (Linking)},
issn = {1087-0156},
journal = {Nature Biotechnology},
number = {9},
pages = {833--838},
pmid = {23907171},
title = {{CAS9 transcriptional activators for target specificity screening and paired nickases for cooperative genome engineering}},
url = {http://www.nature.com/doifinder/10.1038/nbt.2675},
volume = {31},
year = {2013}
}
@article{MacNamara2012,
abstract = {Despite the current wealth of high-throughput data, our understanding of signal transduction is still incomplete. Mathematical modeling can be a tool to gain an insight into such processes. Detailed biochemical modeling provides deep understanding, but does not scale well above relatively a few proteins. In contrast, logic modeling can be used where the biochemical knowledge of the system is sparse and, because it is parameter free (or, at most, uses relatively a few parameters), it scales well to large networks that can be derived by manual curation or retrieved from public databases. Here, we present an overview of logic modeling formalisms in the context of training logic models to data, and specifically the different approaches to modeling qualitative to quantitative data (state) and dynamics (time) of signal transduction. We use a toy model of signal transduction to illustrate how different logic formalisms (Boolean, fuzzy logic and differential equations) treat state and time. Different formalisms allow for different features of the data to be captured, at the cost of extra requirements in terms of computational power and data quality and quantity. Through this demonstration, the assumptions behind each formalism are discussed, as well as their advantages and disadvantages and possible future developments.},
author = {MacNamara, Aidan and Terfve, Camille and Henriques, David and Bernab??, Beatriz Pe??alver and Saez-Rodriguez, Julio},
doi = {10.1088/1478-3975/9/4/045003},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/MacNamara et al. - 2012 - State-time spectrum of signal transduction logic models.pdf:pdf},
isbn = {1478-3975 (Electronic) 1478-3967 (Linking)},
issn = {14783967},
journal = {Physical Biology},
number = {4},
pmid = {22871648},
title = {{State-time spectrum of signal transduction logic models}},
volume = {9},
year = {2012}
}
@article{Shoichet2004,
abstract = {Virtual screening uses computer-based methods to discover new ligands on the basis of biological structures. Although widely heralded in the 1970s and 1980s, the technique has since struggled to meet its initial promise, and drug discovery remains dominated by empirical screening. Recent successes in predicting new ligands and their receptor-bound structures, and better rates of ligand discovery compared to empirical screening, have re-ignited interest in virtual screening, which is now widely used in drug discovery, albeit on a more limited scale than empirical screening.},
author = {Shoichet, B K},
doi = {nature03197 [pii]\r10.1038/nature03197},
isbn = {1476-4687},
issn = {1476-4687},
journal = {Nature},
keywords = {Computer Simulation,Drug Evaluation: Preclinical,Ligands,Models: Molecular,Molecular Conformation,Pharmaceutical Preparations},
number = {7019},
pages = {862--865},
pmid = {15602552},
title = {{Virtual screening of chemical libraries}},
url = {papers://5aa36326-f23d-4d75-b12e-bf93c65dd1bd/Paper/p1983},
volume = {432},
year = {2004}
}
@article{Kembel2006,
abstract = {Numerous ecological and evolutionary processes are thought to play a role in maintaining the high plant species diversity of tropical forests. An understanding of the phylogenetic structure of an ecological community can provide insights into the relative importance of different processes structuring that community. The objectives of this study were to measure the phylogenetic structure of Neotropical forest tree communities in the Forest Dynamics Plot (FDP) on Barro Colorado Island, Panama, to determine how the phylogenetic structure of tree communities varied among spatial scales and habitats within the FDP, and to study the effects of null-model choice on estimates of community phylogenetic structure. We measured community phylogenetic structure for tree species occurring together in quadrats ranging in size from 10 x 10 m to 100 X 100 m in the FDP. We estimated phylogenetic structure by comparing observed phylogenetic distances among species to the distribution of phylogenetic distances for null communities generated using two different null models. A null model that did not maintain observed species occurrence frequencies tended to find nonrandom community phylogenetic structure, even for random data. Using a null model that maintained observed species frequencies in null communities, the average phylogenetic structure of tree communities in the FDP was close to random at all spatial scales examined, but more quadrats than expected contained species that were phylogenetically clustered or overdispersed, and phylogenetic structure varied among habitats. In young forests and plateau habitats, communities were phylogenetically clustered, meaning that trees were more closely related to their neighbors than expected, while communities in swamp and slope habitats were phylogenetically overdispersed, meaning that trees were more distantly related to their neighbors than expected. Phylogenetic clustering suggests the importance of environmental filtering of phylogenetically conserved traits in young forests and plateau habitats, but the phylogenetic overdispersion observed in other habitats has several possible explanations, including variation in the strength of ecological processes among habitats or the phylogenetic history of niches, traits, and habitat associations. Future studies will need to include information on species traits in order to explain the variation in phylogenetic structure among habitats in tropical forests.},
author = {Kembel, Steven W. and Hubbell, Stephen P.},
doi = {10.1890/0012-9658(2006)87[86:TPSOAN]2.0.CO;2},
isbn = {0012-9658},
issn = {00129658},
journal = {Ecology},
keywords = {Community phylogenetic structure,Environmental filtering,Forest Dynamics Plot,Null models,Panama,Phylogenetic clustering,Phylogenetic overdispersion},
number = {7 SUPPL.},
pmid = {16922305},
title = {{The phylogenetic structure of a neotropical forest tree community}},
volume = {87},
year = {2006}
}
@article{Burton-Jones1999,
abstract = {Conceptual modeling is an important task undertaken during the systems development process to build a representation of those features of an application domain that are important to stakeholders. In spite of its importance, however, substantial evidence exists to show that it is not done well. Designers often provide incomplete, inaccurate, or inconsistent representations of domain features in the conceptual models they prepare. Users often have difficulty understanding the meaning inherent in a conceptual model.  In this paper, we investigate the proposition that part of the difficulties that stakeholders experience with conceptual modeling arises when a conceptual modeling grammar or a representation produced using the grammar lacks ontological clarity. Lack of ontological clarity arises when a one-one mapping does not exist between conceptual modeling constructs and real-world constructs. For example, the grammatical construct of an entity is used to represent both things and events in the real world.  Specifically, we focus on the grammatical construct of a relationship with attributes, which is often used in entity-relationship modeling. We argue that use of this construct produces ontologically unclear representations of a domain. We also report results from an experiment we undertook where we investigated the impact of using relationships with attributes in conceptual modeling representations on the problem-solving performance of users of these representations. Consistent with our predictions, we found that using relationships with attributes undermined problem-solving performance in unfamiliar domains. Contrary to our predictions, however, their use did not undermine problem-solving performance in familiar domains.},
author = {Burton-Jones, Andrew and Weber, R},
journal = {Proceedings of the 20th international conference on Information Systems (ICIS)},
keywords = {Conceptual modeling,entity-relationship modeling,experimental research,ontology,perceived ease of understanding,problem solving},
title = {{Understanding relationships with attributes in entity-relationship diagrams}},
year = {1999}
}
@book{Palsson2006,
abstract = {Mycotoxins are small (MW approximately 700), toxic chemical products formed as secondary metabolites by a few fungal species that readily colonise crops and contaminate them with toxins in the field or after harvest. Ochratoxins and Aflatoxins are mycotoxins of major significance and hence there has been significant research on broad range of analytical and detection techniques that could be useful and practical. Due to the variety of structures of these toxins, it is impossible to use one standard technique for analysis and/or detection. Practical requirements for high-sensitivity analysis and the need for a specialist laboratory setting create challenges for routine analysis. Several existing analytical techniques, which offer flexible and broad-based methods of analysis and in some cases detection, have been discussed in this manuscript. There are a number of methods used, of which many are lab-based, but to our knowledge there seems to be no single technique that stands out above the rest, although analytical liquid chromatography, commonly linked with mass spectroscopy is likely to be popular. This review manuscript discusses (a) sample pre-treatment methods such as liquid-liquid extraction (LLE), supercritical fluid extraction (SFE), solid phase extraction (SPE), (b) separation methods such as (TLC), high performance liquid chromatography (HPLC), gas chromatography (GC), and capillary electrophoresis (CE) and (c) others such as ELISA. Further currents trends, advantages and disadvantages and future prospects of these methods have been discussed.},
archivePrefix = {arXiv},
arxivId = {arXiv:1011.1669v3},
author = {Palsson, Bernhard},
booktitle = {Systems Biology: Properties of Reconstructed Networks},
doi = {10.1017/CBO9780511790515},
eprint = {arXiv:1011.1669v3},
isbn = {9780511790515},
issn = {13514180},
pmid = {15991970},
title = {{Systems biology: Properties of reconstructed networks}},
year = {2006}
}
@article{Makinen2012,
abstract = {BACKGROUND: For the development of genome assembly tools, some comprehensive and efficiently computable validation measures are required to assess the quality of the assembly. The mostly used N50 measure summarizes the assembly results by the length of the scaffold (or contig) overlapping the midpoint of the length-order concatenation of scaffolds (contigs). Especially for scaffold assemblies it is non-trivial to combine a correctness measure to the N50 values, and the current methods for doing this are rather involved.$\backslash$n$\backslash$nRESULTS: We propose a simple but rigorous normalized N50 assembly metric that combines N50 with such a correctness measure; assembly is split into as many parts as necessary to align each part to the reference. For scalability, we first compute maximal local approximate matches between scaffolds and reference in distributed manner, and then proceed with co-linear chaining to find a global alignment. Best alignment is removed from the scaffold and the process is iterated with the remaining scaffold content in order to split the scaffold into correctly aligning parts. The proposed normalized N50 metric is then the N50 value computed for the final correctly aligning parts. As a side result of independent interest, we show how to modify co-linear chaining to restrict gaps to produce a more sensible global alignment.$\backslash$n$\backslash$nCONCLUSIONS: We propose and implement a comprehensive and efficient approach to compute a metric that summarizes scaffold assembly correctness and length. Our implementation can be downloaded from http://www.cs.helsinki.fi/group/scaffold/normalizedN50/.},
author = {M{\"{a}}kinen, Veli and Salmela, Leena and Ylinen, Johannes},
doi = {10.1186/1471-2105-13-255},
issn = {1471-2105},
journal = {BMC Bioinformatics},
number = {1},
pages = {255},
pmid = {23031320},
title = {{Normalized N50 assembly metric using gap-restricted co-linear chaining}},
url = {http://bmcbioinformatics.biomedcentral.com/articles/10.1186/1471-2105-13-255},
volume = {13},
year = {2012}
}
@article{Zhang2009a,
abstract = {MOTIVATION: KEGG PATHWAY is a service of Kyoto Encyclopedia of Genes and Genomes (KEGG), constructing manually curated pathway maps that represent current knowledge on biological networks in graph models. While valuable graph tools have been implemented in R/Bioconductor, to our knowledge there is currently no software package to parse and analyze KEGG pathways with graph theory.$\backslash$n$\backslash$nRESULTS: We introduce the software package KEGGgraph in R and Bioconductor, an interface between KEGG pathways and graph models as well as a collection of tools for these graphs. Superior to existing approaches, KEGGgraph captures the pathway topology and allows further analysis or dissection of pathway graphs. We demonstrate the use of the package by the case study of analyzing human pancreatic cancer pathway.$\backslash$n$\backslash$nAVAILABILITY: KEGGgraph is freely available at the Bioconductor web site (http://www.bioconductor.org). KGML files can be downloaded from KEGG FTP site (ftp://ftp.genome.jp/pub/kegg/xml).},
author = {Zhang, Jitao David and Wiemann, Stefan},
doi = {10.1093/bioinformatics/btp167},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Zhang, Wiemann - 2009 - KEGGgraph A graph approach to KEGG PATHWAY in R and bioconductor(2).pdf:pdf},
isbn = {1367-4811 (Linking)},
issn = {13674803},
journal = {Bioinformatics},
pmid = {19307239},
title = {{KEGGgraph: A graph approach to KEGG PATHWAY in R and bioconductor}},
year = {2009}
}
@article{Cosconati2010,
abstract = {IMPORTANCE TO THE FIELD: Virtual screening is a computer-based technique for identifying promising compounds to bind to a target molecule of known structure. Given the rapidly increasing number of protein and nucleic acid structures, virtual screening continues to grow as an effective method for the discovery of new inhibitors and drug molecules. AREAS COVERED IN THIS REVIEW: We describe virtual screening methods that are available in the AutoDock suite of programs, and several of our successes in using AutoDock virtual screening in pharmaceutical lead discovery. WHAT THE READER WILL GAIN: A general overview of the challenges of virtual screening is presented, along with the tools available in the AutoDock suite of programs for addressing these challenges. TAKE HOME MESSAGE: Virtual screening is an effective tool for the discovery of compounds for use as leads in drug discovery, and the free, open source program AutoDock is an effective tool for virtual screening.},
author = {Cosconati, Sandro and Forli, Stefano and Perryman, Alex L and Harris, Rodney and Goodsell, David S and Olson, Arthur J},
doi = {10.1517/17460441.2010.484460},
isbn = {1746-045X (Electronic)$\backslash$n1746-0441 (Linking)},
issn = {1746-0441},
journal = {Expert Opinion on Drug Discovery},
number = {6},
pages = {597--607},
pmid = {21532931},
title = {{Virtual screening with AutoDock: theory and practice}},
url = {http://www.tandfonline.com/doi/full/10.1517/17460441.2010.484460},
volume = {5},
year = {2010}
}
@article{Fernandez2004,
abstract = {Sm-like (Lsm) proteins function in a variety of RNA-processing events. In yeast, the Lsm2-Lsm8 complex binds and stabilizes the spliceosomal U6 snRNA, whereas the Lsm1-Lsm7 complex functions in mRNA decay. Here we report that a third Lsm complex, consisting of Lsm2-Lsm7 proteins, associates with snR5, a box H/ACA snoRNA that functions to guide site-specific pseudouridylation of rRNA. Experiments in which the binding of Lsm proteins to snR5 was reconstituted in vitro reveal that the 3' end of snR5 is critical for Lsm protein recognition. Glycerol gradient sedimentation and sequential immunoprecipitation experiments suggest that the Lsm protein-snR5 complex is partly distinct from the complex formed by snR5 RNA with the box H/ACA proteins Gar1p and Nhp2p. Consistent with a separate complex, Lsm proteins are not required for the function of snR5 in pseudouridylation of rRNA. We demonstrate that in addition to their known nuclear and cytoplasmic locations, Lsm proteins are present in nucleoli. Taken together with previous findings that a small fraction of pre-RNase P RNA associates with Lsm2-Lsm7, our experiments suggest that an Lsm2-Lsm7 protein complex resides in nucleoli, contributing to the biogenesis or function of specific snoRNAs.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Fernandez, Cesar F and Pannone, Barbara K and Chen, Xinguo and Fuchs, Gabriele and Wolin, Sandra L},
doi = {10.1091/mbc.E04-02-0116},
eprint = {NIHMS150003},
isbn = {1059-1524 (Print)},
issn = {1059-1524},
journal = {Molecular biology of the cell},
keywords = {Base Sequence,Cell Nucleolus,Cell Nucleolus: metabolism,Molecular Sequence Data,Multiprotein Complexes,Protein Binding,RNA, Fungal,RNA, Fungal: chemistry,RNA, Fungal: genetics,RNA, Fungal: metabolism,RNA, Small Nucleolar,RNA, Small Nucleolar: chemistry,RNA, Small Nucleolar: genetics,RNA, Small Nucleolar: metabolism,Ribonucleoproteins, Small Nuclear,Ribonucleoproteins, Small Nuclear: genetics,Ribonucleoproteins, Small Nuclear: metabolism,Saccharomyces cerevisiae,Saccharomyces cerevisiae Proteins,Saccharomyces cerevisiae Proteins: genetics,Saccharomyces cerevisiae Proteins: metabolism,Saccharomyces cerevisiae: genetics,Saccharomyces cerevisiae: metabolism,Substrate Specificity},
number = {6},
pages = {2842--52},
pmid = {15075370},
title = {{An Lsm2-Lsm7 complex in Saccharomyces cerevisiae associates with the small nucleolar RNA snR5.}},
url = {http://www.molbiolcell.org/content/15/6/2842.long},
volume = {15},
year = {2004}
}
@misc{Bromberg2000,
abstract = {The STAT proteins (Signal Transducers and Activators of Transcription), were identified in the last decade as transcription factors which were critical in mediating virtually all cytokine driven signaling. These proteins are latent in the cytoplasm and become activated through tyrosine phosphorylation which typically occurs through cytokine receptor associated kinases (JAKs) or growth factor receptor tyrosine kinases. Recently a number of non-receptor tyrosine kinases (for example src and abl) have been found to cause STAT phosphorylation. Phosphorylated STATs form homo- or hetero-dimers, enter the nucleus and working coordinately with other transcriptional co-activators or transcription factors lead to increased transcriptional initiation. In normal cells and in animals, ligand dependent activation of the STATs is a transient process, lasting for several minutes to several hours. In contrast, in many cancerous cell lines and tumors, where growth factor dysregulation is frequently at the heart of cellular transformation, the STAT proteins (in particular Stats 1, 3 and 5) are persistently tyrosine phosphorylated or activated. The importance of STAT activation to growth control in experiments using anti-sense molecules or dominant negative STAT protein encoding constructs performed in cell lines or studies in animals lacking specific STATs strongly indicate that STATs play an important role in controlling cell cycle progression and apoptosis. Stat1 plays an important role in growth arrest, in promoting apoptosis and is implicated as a tumor suppressor; while Stats 3 and 5 are involved in promoting cell cycle progression and cellular transformation and preventing apoptosis. Many questions remain including: (1) a better understanding of how the STAT proteins through association with other factors increase transcription initiation; (2) a more complete definition of the sets of genes which are activated by different STATs and (3) how these sets of activated genes differ as a function of cell type. Finally, in the context of many cancers, where STATs are frequently persistently activated, an understanding of the mechanisms leading to their constitutive activation and defining the potential importance of persistent STAT activation in human tumorigenesis remains. Oncogene (2000).},
author = {Bromberg, Jacqueline and Darnell, James E.},
booktitle = {Oncogene},
doi = {10.1038/sj.onc.1203476},
isbn = {0950-9232 (Print)$\backslash$n0950-9232 (Linking)},
issn = {09509232},
keywords = {Cancer,Growth control,STAT,Signal transduction,Transcription},
pmid = {10851045},
title = {{The role of STATs in transcriptional control and their impact on cellular function}},
year = {2000}
}
@article{Schulze2005,
abstract = {Interactions between short modified peptide motifs and modular protein domains are central events in cell signal-transduction. We determined interaction partners to all cytosolic tyrosine residues of the four members of the ErbB-receptor family in an unbiased fashion by quantitative proteomics using pull-down experiments with pairs of phosphorylated and nonphosphorylated synthetic peptides. Each receptor had characteristic preferences for interacting proteins and most interaction partners had multiple binding sites on each receptor. EGFR and ErbB4 had several docking sites for Grb2, while ErbB3 was characterized by six binding sites for PI3K. We identified STAT5 as a direct binding partner to EGFR and ErbB4 and discovered new recognition motifs for Shc and STAT5. The overall pattern of interaction partners of EGFR and ErbB4 suggests similar roles during signaling through their respective ligands. Phosphorylation kinetics of several tyrosine resides was measured by mass spectrometry and correlated with interaction partner preference. Our results demonstrate that system-wide mapping of peptide-protein interactions sites is possible, and suggest shared and unique roles of ErbB-receptor family members in downstream signaling.},
author = {Schulze, Waltraud X and Deng, Lei and Mann, Matthias},
doi = {10.1038/msb4100012},
isbn = {1744-4292 (Electronic)$\backslash$r1744-4292 (Linking)},
issn = {1744-4292},
journal = {Molecular Systems Biology},
pmid = {16729043},
title = {{Phosphotyrosine interactome of the ErbB-receptor kinase family}},
year = {2005}
}
@article{Kanehisa2009,
abstract = {Most human diseases are complex multi-factorial diseases resulting from the combination of various genetic and environmental factors. In the KEGG database resource (http://www.genome.jp/kegg/), diseases are viewed as perturbed states of the molecular system, and drugs as perturbants to the molecular system. Disease information is computerized in two forms: pathway maps and gene/molecule lists. The KEGG PATHWAY database contains pathway maps for the molecular systems in both normal and perturbed states. In the KEGG DISEASE database, each disease is represented by a list of known disease genes, any known environmental factors at the molecular level, diagnostic markers and therapeutic drugs, which may reflect the underlying molecular system. The KEGG DRUG database contains chemical structures and/or chemical components of all drugs in Japan, including crude drugs and TCM (Traditional Chinese Medicine) formulas, and drugs in the USA and Europe. This database also captures knowledge about two types of molecular networks: the interaction network with target molecules, metabolizing enzymes, other drugs, etc. and the chemical structure transformation network in the history of drug development. The new disease/drug information resource named KEGG MEDICUS can be used as a reference knowledge base for computational analysis of molecular networks, especially, by integrating large-scale experimental datasets.},
author = {Kanehisa, Minoru and Goto, Susumu and Furumichi, Miho and Tanabe, Mao and Hirakawa, Mika},
doi = {10.1093/nar/gkp896},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Kanehisa et al. - 2009 - KEGG for representation and analysis of molecular networks involving diseases and drugs(2).pdf:pdf},
isbn = {1362-4962 (Electronic)$\backslash$r0305-1048 (Linking)},
issn = {03051048},
journal = {Nucleic Acids Research},
number = {SUPPL.1},
pages = {355--360},
pmid = {19880382},
title = {{KEGG for representation and analysis of molecular networks involving diseases and drugs}},
volume = {38},
year = {2009}
}
@article{Bernado2005,
abstract = {Natively unfolded proteins play key roles in normal and pathological biochemical  processes. Despite their importance for function, this category of proteins remains beyond the reach of classical structural biology because of their inherent conformational heterogeneity. We present a description of the intrinsic conformational sampling of unfolded proteins based on residue-specific /Psi propensities from loop regions of a folded protein database and simple volume exclusion. This approach is used to propose a structural model of the 57-aa, natively disordered region of the nucleocapsid-binding domain of Sendai virus phosphoprotein. Structural ensembles obeying these simple rules of conformational sampling are used to simulate averaged residual dipolar couplings (RDCs) and small-angle x-ray scattering data. This protein is particularly informative because RDC data from the equally sized folded and unfolded domains both report on the unstructured region, allowing a quantitative analysis of the degree of order present in this part of the protein. Close agreement between experimental and simulated RDC and small-angle x-ray scattering data validates this simple model of conformational sampling, providing a precise description of local structure and dynamics and average dimensions of the ensemble of sampled structures. RDC data from two urea-unfolded systems are also closely reproduced. The demonstration that conformational behavior of unfolded proteins can be accurately predicted from the primary sequence by using a simple set of rules has important consequences for our understanding of the structure and dynamics of the unstructured state.},
author = {Bernado, Pau and Blanchard, Laurence and Timmins, Peter and Marion, Dominique and Ruigrok, Rob W H and Blackledge, Martin},
doi = {10.1073/pnas.0506202102},
isbn = {0027-8424 (Print)$\backslash$r0027-8424 (Linking)},
issn = {0027-8424 (Print)},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
keywords = {Models, Molecular,Phosphoproteins,Protein Denaturation,Protein Structure, Tertiary,Scattering, Radiation,Sendai virus,Sequence Analysis, Protein,Urea,Viral Proteins,X-Ray Diffraction,X-Rays,chemistry},
number = {47},
pages = {17002--17007},
pmid = {16284250},
title = {{A structural model for unfolded proteins from residual dipolar couplings and small-angle x-ray scattering.}},
volume = {102},
year = {2005}
}
@article{Yvert2013,
abstract = {BACKGROUND:Most quantitative measures of phenotypic traits represent macroscopic contributions of large numbers of cells. Yet, cells of a tissue do not behave similarly, and molecular studies on several organisms have shown that regulations can be highly stochastic, sometimes generating diversified cellular phenotypes within tissues. Phenotypic noise, defined here as trait variability among isogenic cells of the same type and sharing a common environment, has therefore received a lot of attention. Given the potential fitness advantage provided by phenotypic noise in fluctuating environments, the possibility that it is directly subjected to evolutionary selection is being considered. For selection to act, phenotypic noise must differ between contemporary genotypes. Whether this is the case or not remains, however, unclear because phenotypic noise has very rarely been quantified in natural populations.$\backslash$n$\backslash$nRESULTS:Using automated image analysis, we describe here the phenotypic diversity of S. cerevisiae morphology at single-cell resolution. We profiled hundreds of quantitative traits in more than 1,000 cells of 37 natural strains, which represent various geographical and ecological origins of the species. We observed abundant trait variation between strains, with no correlation with their ecological origin or population history. Phenotypic noise strongly depended on the strain background. Noise variation was largely trait-specific (specific strains showing elevated noise for subset of traits) but also global (a few strains displaying elevated noise for many unrelated traits).$\backslash$n$\backslash$nCONCLUSIONS:Our results demonstrate that phenotypic noise does differ quantitatively between natural populations. This supports the possibility that, if noise is adaptive, microevolution may tune it in the wild. This tuning may happen on specific traits or by varying the degree of global phenotypic buffering.},
author = {Yvert, Ga{\"{e}}l and Ohnuki, Shinsuke and Nogami, Satoru and Imanaga, Yasutaka and Fehrmann, Steffen and Schacherer, Joseph and Ohya, Yoshikazu},
doi = {10.1186/1752-0509-7-54},
isbn = {1752050975},
issn = {1752-0509},
journal = {BMC Systems Biology},
number = {1},
pages = {54},
pmid = {23822767},
title = {{Single-cell phenomics reveals intra-species variation of phenotypic noise in yeast}},
url = {http://bmcsystbiol.biomedcentral.com/articles/10.1186/1752-0509-7-54},
volume = {7},
year = {2013}
}
@article{Pelicci1992,
abstract = {A new SH2-containing sequence, SHC, was isolated by screening cDNA libraries with SH2 representative DNA probes. The SHC cDNA is predicted to encode overlapping proteins of 46.8 and 51.7 kd that contain a single C-terminal SH2 domain, and an adjacent glycine/proline-rich motif with regions of homology with the $\alpha$1 chain of collagen, but no identifiable catalytic domain. Anti-SHC antibodies recognized three proteins of 46, 52, and 66 kd in a wide range of mammalian cell lines. These SHC proteins complexed with and were phosphorylated by activated epidermal growth factor receptor. The physical association of SHC proteins with activated receptors was recreated in vitro by using a bacterially expressed SHC SH2 domain. NIH 3T3 mouse fibroblasts that constitutively overexpressed SHC acquired a transformed phenotype in culture and formed tumors in nude mice. These results suggest that the SHC gene products couple activated growth factor receptors to a signaling pathway that regulates the proliferation of mammalian cells. {\textcopyright} 1992.},
author = {Pelicci, Giuliana and Lanfrancone, Luisa and Grignani, Francesco and McGlade, Jane and Cavallo, Federica and Forni, Guido and Nicoletti, Ildo and Grignani, Fausto and Pawson, Tony and {Giuseppe Pelicci}, Pier},
doi = {10.1016/0092-8674(92)90536-L},
isbn = {0092-8674 (Print)$\backslash$n0092-8674 (Linking)},
issn = {00928674},
journal = {Cell},
pmid = {1623525},
title = {{A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction}},
year = {1992}
}
@article{Colomiere2008,
author = {Colomiere, M and Ward, A C and Riley, C and Trenerry, M K and Cameron-Smith, D and Findlay, J and Ackland, L and Ahmed, N},
journal = {British Journal Of Cancer},
month = {dec},
pages = {134},
publisher = {The Author(s)},
title = {{Cross talk of signals between EGFR and IL-6R through JAK2/STAT3 mediate epithelial–mesenchymal transition in ovarian carcinomas}},
url = {https://doi.org/10.1038/sj.bjc.6604794 http://10.0.4.14/sj.bjc.6604794 https://www.nature.com/articles/6604794{\#}supplementary-information},
volume = {100},
year = {2008}
}
@article{Zhang2009b,
abstract = {MOTIVATION: KEGG PATHWAY is a service of Kyoto Encyclopedia of Genes and Genomes (KEGG), constructing manually curated pathway maps that represent current knowledge on biological networks in graph models. While valuable graph tools have been implemented in R/Bioconductor, to our knowledge there is currently no software package to parse and analyze KEGG pathways with graph theory.$\backslash$n$\backslash$nRESULTS: We introduce the software package KEGGgraph in R and Bioconductor, an interface between KEGG pathways and graph models as well as a collection of tools for these graphs. Superior to existing approaches, KEGGgraph captures the pathway topology and allows further analysis or dissection of pathway graphs. We demonstrate the use of the package by the case study of analyzing human pancreatic cancer pathway.$\backslash$n$\backslash$nAVAILABILITY: KEGGgraph is freely available at the Bioconductor web site (http://www.bioconductor.org). KGML files can be downloaded from KEGG FTP site (ftp://ftp.genome.jp/pub/kegg/xml).},
author = {Zhang, Jitao David and Wiemann, Stefan},
doi = {10.1093/bioinformatics/btp167},
file = {:Users/ozlem/Dropbox/papers/KEGGgraph.pdf:pdf},
isbn = {1367-4811 (Linking)},
issn = {13674803},
journal = {Bioinformatics},
number = {11},
pages = {1470--1471},
pmid = {19307239},
title = {{KEGGgraph: A graph approach to KEGG PATHWAY in R and bioconductor}},
volume = {25},
year = {2009}
}
@article{Huelsenbeck1991,
abstract = {Computer simulations in which phylogenies were generated under various conditions were used to examine the relationship between the phylogenetic signal of a character data set, the skewness of the tree-length distribution, and the position of the real tree relative to the most parsimonious tree for a four-character-state system. Character data that are consistent with one phylogenetic hypothesis produce tree-length distributions that are highly skewed to the left, whereas character data consistent with many phylogenetic hypotheses produce more symmetrical tree-length distributions that cannot be distinguished from tree-length distributions produced by random character data. The relationship between the skewness of the tree-length distribution, as measured by the g1 statistic, and the amount of phylogenetic signal varies depending on tree topology, the proportion of the sequence that is informative (e.g., informative change at only the first codon position as opposed to informative change at the first and second codon positions), and the number of sequence data. However, in all simulations that produced tree-length distributions that were significant at the 1{\%} level under Hillis's (1991, in Phylogenetic analysis of DNA sequences [M. M. Miyamoto and J. Cracraft, eds.], Oxford Univ. Press, Oxford, England [in press]) statistical test, the real tree was very close to or was the most parsimonious tree. Conversely, in trees with nonsignificantly skewed tree-length distributions, the real tree could be almost anywhere in the distribution. However, the real tree tended to be closer to the most parsimonious tree than would be expected at random. This study suggests that tree-length distribution skewness provides a useful criterion for judging the phylogenetic information content of character data.},
author = {Huelsenbeck, John P.},
doi = {10.1093/sysbio/40.3.257},
isbn = {00397989},
issn = {1076836X},
journal = {Systematic Biology},
number = {3},
pages = {257--270},
title = {{Tree-length distribution skewness: An indicator of phylogenetic information}},
volume = {40},
year = {1991}
}
@article{Franklin2012,
abstract = {Exposure to stressful events can be differently perceived by individuals and can have persistent sequelae depending on the level of stress resilience or vulnerability of each person. The neural processes that underlie such clinically and socially important differences reside in the anatomical, functional, and molecular connectivity of the brain. Recent work has provided novel insight into some of the involved biological mechanisms that promises to help prevent and treat stress-related disorders. In this review, we focus on causal and mechanistic evidence implicating altered functions and connectivity of the neuroendocrine system, and of hippocampal, cortical, reward, and serotonergic circuits in the establishment and the maintenance of stress resilience and vulnerability. We also touch upon recent findings suggesting a role for epigenetic mechanisms and neurogenesis in these processes and briefly discuss promising avenues of future investigation.},
author = {Franklin, Tamara B. and Saab, Bechara J. and Mansuy, Isabelle M.},
doi = {10.1016/j.neuron.2012.08.016},
file = {:Users/ozlem/Desktop/PIIS0896627312007532.pdf:pdf},
isbn = {1097-4199 (Electronic)$\backslash$n0896-6273 (Linking)},
issn = {08966273},
journal = {Neuron},
number = {5},
pages = {747--761},
pmid = {22958817},
publisher = {Elsevier Inc.},
title = {{Neural Mechanisms of Stress Resilience and Vulnerability}},
url = {http://dx.doi.org/10.1016/j.neuron.2012.08.016},
volume = {75},
year = {2012}
}
@article{Horowitz2018,
abstract = {Cancer-related cognitive impairment (CRCI) is a widespread problem for the increasing population of cancer survivors. Our understanding of the nature, causes, and prevalence of CRCI is hampered by a reliance on clinical neuropsychological methods originally designed to detect focal lesions. Future progress will require collaboration between neuroscience and clinical neuropsychology.},
author = {Horowitz, Todd S. and Suls, Jerry and Trevi{\~{n}}o, Melissa},
doi = {10.1016/j.tins.2018.05.001},
file = {:Users/ozlem/Desktop/1F08EFCC-3EC1-4219-BA2C-5083C0A54047.pdf:pdf},
issn = {1878108X},
journal = {Trends in Neurosciences},
keywords = {cancer,chemobrain,chemotherapy,cognitive impairment,neuroimaging,neuropsychological tests,survivorship},
pages = {3--5},
pmid = {29907436},
publisher = {Elsevier Ltd},
title = {{A Call for a Neuroscience Approach to Cancer-Related Cognitive Impairment}},
url = {https://doi.org/10.1016/j.tins.2018.05.001},
volume = {xx},
year = {2018}
}
@article{LeNovere2015,
abstract = {Behaviours of complex biomolecular systems are often irreducible to the elementary properties of their individual components. Explanatory and predictive mathematical models are therefore useful for fully understanding and precisely engineering cellular functions. The development and analyses of these models require their adaptation to the problems that need to be solved and the type and amount of available genetic or molecular data. Quantitative and logic modelling are among the main methods currently used to model molecular and gene networks. Each approach comes with inherent advantages and weaknesses. Recent developments show that hybrid approaches will become essential for further progress in synthetic biology and in the development of virtual organisms.},
author = {{Le Novere}, Nicolas},
doi = {10.1038/nrg3885},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Le Novere - 2015 - Quantitative and logic modelling of molecular and gene networks.pdf:pdf},
isbn = {1471-0056$\backslash$r1471-0064},
issn = {14710064},
journal = {Nature Reviews Genetics},
number = {3},
pages = {146--158},
pmid = {25645874},
title = {{Quantitative and logic modelling of molecular and gene networks}},
volume = {16},
year = {2015}
}
@article{Swainston2011,
abstract = {The generation and use of metabolic network reconstructions has increased over recent years. The development of such reconstructions has typically involved a time-consuming, manual process. Recent work has shown that steps undertaken in reconstructing such metabolic networks are amenable to automation. The SuBliMinaL Toolbox (http://www.mcisb.org/subliminal/) facilitates the reconstruction process by providing a number of independent modules to perform common tasks, such as generating draft reconstructions, determining metabolite protonation state, mass and charge balancing reactions, suggesting intracellular compartmentalisation, adding transport reactions and a biomass function, and formatting the reconstruction to be used in third-party analysis packages. The individual modules manipulate reconstructions encoded in Systems Biology Markup Language (SBML), and can be chained to generate a reconstruction pipeline, or used individually during a manual curation process. This work describes the individual modules themselves, and a study in which the modules were used to develop a metabolic reconstruction of Saccharomyces cerevisiae from the existing data resources KEGG and MetaCyc. The automatically generated reconstruction is analysed for blocked reactions, and suggestions for future improvements to the toolbox are discussed.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Swainston, Neil and Smallbone, Kieran and Mendes, Pedro and Kell, Douglas and Paton, Norman},
doi = {10.2390/biecoll-jib-2011-186},
eprint = {NIHMS150003},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Swainston et al. - 2011 - The SuBliMinaL Toolbox automating steps in the reconstruction of metabolic networks.pdf:pdf},
isbn = {1613-4516 (Electronic)$\backslash$r1613-4516 (Linking)},
issn = {1613-4516},
journal = {Journal of integrative bioinformatics},
keywords = {Computer Simulation,Metabolic Networks and Pathways,Saccharomyces cerevisiae,Saccharomyces cerevisiae: metabolism,Software,Systems Biology},
number = {2},
pages = {186},
pmid = {22095399},
title = {{The SuBliMinaL Toolbox: automating steps in the reconstruction of metabolic networks.}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/22095399},
volume = {8},
year = {2011}
}
@article{Wang2012c,
abstract = {Mathematical modeling of biological processes provides deep insights into complex cellular systems. While quantitative and continuous models such as differential equations have been widely used, their use is obstructed in systems wherein the knowledge of mechanistic details and kinetic parameters is scarce. On the other hand, a wealth of molecular level qualitative data on individual components and interactions can be obtained from the experimental literature and high-throughput technologies, making qualitative approaches such as Boolean network modeling extremely useful. In this paper, we build on our research to provide a methodology overview of Boolean modeling in systems biology, including Boolean dynamic modeling of cellular networks, attractor analysis of Boolean dynamic models, as well as inferring biological regulatory mechanisms from high-throughput data using Boolean models. We finally demonstrate how Boolean models can be applied to perform the structural analysis of cellular networks. This overview aims to acquaint life science researchers with the basic steps of Boolean modeling and its applications in several areas of systems biology.},
author = {Wang, Rui-Sheng and Saadatpour, Assieh and Albert, R{\'{e}}ka},
doi = {10.1088/1478-3975/9/5/055001},
isbn = {1478-3967},
issn = {1478-3967},
journal = {Physical Biology},
pmid = {23011283},
title = {{Boolean modeling in systems biology: an overview of methodology and applications}},
year = {2012}
}
@article{Anjum2008,
author = {Anjum, Rana and Blenis, John},
journal = {Nature Reviews Molecular Cell Biology},
month = {oct},
pages = {747},
publisher = {Nature Publishing Group},
title = {{The RSK family of kinases: emerging roles in cellular signalling}},
url = {https://doi.org/10.1038/nrm2509 http://10.0.4.14/nrm2509 https://www.nature.com/articles/nrm2509{\#}supplementary-information},
volume = {9},
year = {2008}
}
@article{Morris2009,
abstract = {We herein present the graphical user interface (GUI) TmoleX for the quantum chemical program package TURBOMOLE. TmoleX allows users to execute the complete workflow of a quantum chemical investigation from the initial building of a structure to the visualization of the results in a user friendly graphical front end. The purpose of TmoleX is to make TURBOMOLE easy to use and to provide a high degree of flexibility. Hence, it should be a valuable tool for most users from beginners to experts. The program is developed in Java and runs on Linux, Windows, and Mac platforms. It can be used to run calculations on local desktops as well as on remote computers.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Morris, Gm and Huey, Ruth},
doi = {10.1002/jcc.21256.AutoDock4},
eprint = {NIHMS150003},
isbn = {1096-987X},
issn = {1096-987X},
journal = {Journal of {\ldots}},
keywords = {autodock,computational docking,computer-aided drug,covalent ligands,protein flexibility},
number = {16},
pages = {2785--2791},
pmid = {20928852},
title = {{AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility}},
volume = {30},
year = {2009}
}
@article{Harris2003,
abstract = {The mammalian target of rapamycin, mTOR, is a protein Ser-Thr kinase that functions as a central element in a signaling pathway involved in the control of cell growth and proliferation. The activity of mTOR is controlled not only by amino acids, but also by hormones and growth factors that activate the protein kinase Akt. The signaling pathway downstream of Akt leading to mTOR involves the protein products of the genes mutated in tuberous sclerosis, TSC1 and TSC2, and the small guanosine triphosphatase, Rheb. In cells, mTOR is found in a complex with two other proteins, raptor and mLST8. In this review, we describe recent progress in understanding the control of the mTOR signaling pathway and the role of mTOR-interacting proteins.},
author = {Harris, T. E. and Lawrence, J. C.},
doi = {10.1126/stke.2122003re15},
isbn = {1525-8882 (Electronic)$\backslash$r1525-8882 (Linking)},
issn = {1945-0877},
journal = {Science Signaling},
pmid = {14668532},
title = {{TOR Signaling}},
year = {2003}
}
@misc{Singh2017,
abstract = {CRISPR-Cas9 is an RNA-mediated adaptive immune system that protects bacteria and archaea from viruses or plasmids. Herein we discuss the recent development of CRISPR-Cas9 into a key technology for genome editing, targeting, and regulation in a wide range of organisms and cell types. It requires a custom designed single guide-RNA (sgRNA), a Cas9 endonuclease, and PAM sequences in the target region. The sgRNA-Cas9 complex binds to its target and creates a double-strand break (DSB) that can be repaired by non-homologous end joining (NHEJ) or by the homology-directed repair (HDR) pathway, modifying or permanently replacing the genomic target sequence. Additionally, we highlight recent advances in the repurposing of CRISPR-Cas9 for repression, activation, and loci imaging. In this review, we underline the current progress and the future potential of the CRISPR-Cas9 system towards biomedical, therapeutic, industrial, and biotechnological applications.},
author = {Singh, Vijai and Braddick, Darren and Dhar, Pawan Kumar},
booktitle = {Gene},
doi = {10.1016/j.gene.2016.11.008},
isbn = {1879-0038 (Electronic)
0378-1119 (Linking)},
issn = {18790038},
keywords = {Activation,CRISPR-Cas9,CRISPRi,Gene therapy,Genome editing,Indel,Repression,sgRNA},
pages = {1--18},
pmid = {27836667},
title = {{Exploring the potential of genome editing CRISPR-Cas9 technology}},
volume = {599},
year = {2017}
}
@article{Long2014,
abstract = {Duchenne muscular dystrophy (DMD) is an inherited X-linked disease caused by mutations in the gene encoding dystrophin, a protein required for muscle fiber integrity. DMD is characterized by progressive muscle weakness and a shortened life span, and there is no effective treatment. We used CRISPR/Cas9-mediated genome editing to correct the dystrophin gene (Dmd) mutation in the germline of mdx mice, a model for DMD, and then monitored muscle structure and function. Genome editing produced genetically mosaic animals containing 2 to 100{\%} correction of the Dmd gene. The degree of muscle phenotypic rescue in mosaic mice exceeded the efficiency of gene correction, likely reflecting an advantage of the corrected cells and their contribution to regenerating muscle. With the anticipated technological advances that will facilitate genome editing of postnatal somatic cells, this strategy may one day allow correction of disease-causing mutations in the muscle tissue of patients with DMD.},
author = {Long, C. and McAnally, J. R. and Shelton, J. M. and Mireault, A. A. and Bassel-Duby, R. and Olson, E. N.},
doi = {10.1126/science.1254445},
isbn = {1095-9203 (Electronic)$\backslash$r0036-8075 (Linking)},
issn = {0036-8075},
journal = {Science},
number = {6201},
pages = {1184--1188},
pmid = {25123483},
title = {{Prevention of muscular dystrophy in mice by CRISPR/Cas9-mediated editing of germline DNA}},
url = {http://www.sciencemag.org/cgi/doi/10.1126/science.1254445},
volume = {345},
year = {2014}
}
@incollection{Chen2002,
abstract = {This paper describes the historical developments of the Entity-Relationship (ER) model from the 1970s to recent years. It starts with a discussion of the motivations and environmental factors in the early days. Then, the paper points out the role of the ER model in the Computer-Aided Software Engineering (CASE) movement in the late 1980s and early 1990s. It also describes the possible role of the author's Chinese cultural heritage in the development of the ER model. In that context, the relationships between natural languages (including Ancient Egyptian hieroglyphics) and ER concepts are explored. Finally, the lessons learned and future directions are presented.},
author = {Chen, Peter},
booktitle = {Software Pioneers},
doi = {10.1007/978-3-642-59412-0_17},
isbn = {978-3-642-63970-8},
issn = {03855236},
pmid = {23398579},
title = {{Entity-Relationship Modeling: Historical Events, Future Trends, and Lessons Learned}},
year = {2002}
}
@article{Rosenfeld2003,
abstract = {The W191G cavity of cytochrome c peroxidase is useful as a model system for introducing small molecule oxidation in an artificially created cavity. A set of small, cyclic, organic cations was previously shown to bind in the buried, solvent-filled pocket created by the W191G mutation. We docked these ligands and a set of non-binders in the W191G cavity using AutoDock 3.0. For the ligands, we compared docking predictions with experimentally determined binding energies and X-ray crystal structure complexes. For the ligands, predicted binding energies differed from measured values by +/- 0.8 kcal/mol. For most ligands, the docking simulation clearly predicted a single binding mode that matched the crystallographic binding mode within 1.0 A RMSD. For 2 ligands, where the docking procedure yielded an ambiguous result, solutions matching the crystallographic result could be obtained by including an additional crystallographically observed water molecule in the protein model. For the remaining 2 ligands, docking indicated multiple binding modes, consistent with the original electron density, suggesting disordered binding of these ligands. Visual inspection of the atomic affinity grid maps used in docking calculations revealed two patches of high affinity for hydrogen bond donating groups. Multiple solutions are predicted as these two sites compete for polar hydrogens in the ligand during the docking simulation. Ligands could be distinguished, to some extent, from non-binders using a combination of two trends: predicted binding energy and level of clustering. In summary, AutoDock 3.0 appears to be useful in predicting key structural and energetic features of ligand binding in the W191G cavity.},
author = {Rosenfeld, Robin J. and Goodsell, David S. and Musah, Rabi A. and Morris, Garrett M. and Goodin, David B. and Olson, Arthur J.},
doi = {10.1023/B:JCAM.0000004604.87558.02},
isbn = {0920-654X (Print)$\backslash$n0920-654X (Linking)},
issn = {0920654X},
journal = {Journal of Computer-Aided Molecular Design},
keywords = {AutoDock,Automated docking,Binding free energy,Cytochrome c peroxidase,Protein engineering,Protein-ligand interaction},
number = {8},
pages = {525--536},
pmid = {14703123},
title = {{Automated docking of ligands to an artificial active site: Augmenting crystallographic analysis with computer modeling}},
volume = {17},
year = {2003}
}
@article{Nicaud2012,
abstract = {The construction of mitotically stable yeast strains for heterologous gene or pathway expression often requires chromosomal integration. However, transcription levels vary between different chromosome regions. We therefore characterized 20 different integration sites of the Sacchromyces cerevisiae genome by inserting lacZ as a reporter gene under the control of two different promoters and determining expression levels through enzyme activity measurement. An up to 8.7-fold difference was detected between the sites conferring lowest and highest expression, respectively. This opens the opportunity for modulating gene expression levels while retaining promoter and culture conditions.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Nicaud, Jean-Marc},
doi = {10.1002/yea.2921},
eprint = {NIHMS150003},
isbn = {1097-0061 (Electronic)$\backslash$r0749-503X (Linking)},
issn = {0749503X},
journal = {Yeast},
keywords = {b -tubulin gene,dna barcoding,species-,wickerhamomyces anomalus},
number = {10},
pages = {409--418},
pmid = {19681174},
title = {{Yarrowia lipolytica}},
url = {http://doi.wiley.com/10.1002/yea.2921},
volume = {29},
year = {2012}
}
@article{Mulleder2016,
abstract = {Genome-metabolism interactions enable cell growth. To probe the extent of these interactions and delineate their functional contributions, we quantified the Saccharomyces amino acid metabolome and its response to systematic gene deletion. Over one-third of coding genes, in particular those important for chromatin dynamics, translation, and transport, contribute to biosynthetic metabolism. Specific amino acid signatures characterize genes of similar function. This enabled us to exploit functional metabolomics to connect metabolic regulators to their effectors, as exemplified by TORC1, whose inhibition in exponentially growing cells is shown to match an interruption in endomembrane transport. Providing orthogonal information compared to physical and genetic interaction networks, metabolomic signatures cluster more than half of the so far uncharacterized yeast genes and provide functional annotation for them. A major part of coding genes is therefore participating in gene-metabolism interactions that expose the metabolism regulatory network and enable access to an underexplored space in gene function.},
author = {M{\"{u}}lleder, Michael and Calvani, Enrica and Alam, Mohammad Tauqeer and Wang, Richard Kangda and Eckerstorfer, Florian and Zelezniak, Aleksej and Ralser, Markus},
doi = {10.1016/j.cell.2016.09.007},
isbn = {0092-8674},
issn = {10974172},
journal = {Cell},
keywords = {amino acids,functional gene annotation,functional metabolomics,mass spectrometry,metabolism,target of rapamycin (TOR),unknown gene function,vesicle mediated transport,yeast gene deletion collection},
number = {2},
pages = {553--565.e12},
pmid = {27693354},
title = {{Functional Metabolomics Describes the Yeast Biosynthetic Regulome}},
volume = {167},
year = {2016}
}
@misc{Bruggeman2007a,
abstract = {The advent of functional genomics has enabled the molecular biosciences to come a long way towards characterizing the molecular constituents of life. Yet, the challenge for biology overall is to understand how organisms function. By discovering how function arises in dynamic interactions, systems biology addresses the missing links between molecules and physiology. Top-down systems biology identifies molecular interaction networks on the basis of correlated molecular behavior observed in genome-wide 'omics' studies. Bottom-up systems biology examines the mechanisms through which functional properties arise in the interactions of known components. Here, we outline the challenges faced by systems biology and discuss limitations of the top-down and bottom-up approaches, which, despite these limitations, have already led to the discovery of mechanisms and principles that underlie cell function. {\textcopyright} 2006 Elsevier Ltd. All rights reserved.},
author = {Bruggeman, Frank J. and Westerhoff, Hans V.},
booktitle = {Trends in Microbiology},
doi = {10.1016/j.tim.2006.11.003},
isbn = {0966-842X},
issn = {0966842X},
pmid = {17113776},
title = {{The nature of systems biology}},
year = {2007}
}
@article{Okabayashi1994,
abstract = {Autophosphorylation of receptor tyrosine kinases provides binding sites for signaling proteins containing Src homology 2 (SH2) domains. We determined the binding sites of Shc, SH2-containing adaptor protein, within epidermal growth factor (EGF) receptors, using Chinese hamster ovary cells overexpressing EGF receptor mutants in which autophosphorylation sites, either alone or in combination, were replaced by phenylalanine. Binding of Shc to EGF receptor mutants lacking single tyrosine residues at 1148 or 1173 decreased by approximately 60 or approximately 15{\%}, respectively, whereas other single point mutants bound the wild-type level of Shc. Binding of Shc markedly decreased in mutants lacking both tyrosine residues at 1148 and 1173. In peptide inhibition assay, phosphorylated nonameric peptide representing tyrosine 1148, DNPDpYQQDF, but not pentameric peptide, pYQQDF, inhibited the binding of glutathione S-transferase-Shc SH2 domain fusion protein to in vitro autophosphorylated EGF receptors, suggesting that N-terminal sequences adjacent to phosphotyrosine are necessary for the association of Shc. Based on results of peptide inhibition assays in which phosphorylated peptides representing tyrosines 992, 1148, and 1173 inhibited Shc binding to the receptor, we constructed another EGF receptor mutant in which one of these tyrosine residues was retained. The amount of Shc bound to mutant receptors retaining tyrosines 1148, 1173, or 992 was approximately 80, approximately 40, or approximately 10{\%} of wild-type level, respectively. These results indicate that tyrosine 1148 of activated human EGF receptors is a major binding site of Shc and tyrosine 1173 is a secondary binding site in intact cells.},
author = {Okabayashi, Yoshinori and Kido, Yoshiaki and Okutani, Toshio and Sugimoto, Yutaka and Sakaguchi, Kazuhiko and Kasuga, Masato},
isbn = {9781742497211},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {8034616},
title = {{Tyrosines 1148 and 1173 of activated human epidermal growth factor receptors are binding sites of Shc in intact cells}},
year = {1994}
}
@article{Ramos-Perez2017,
abstract = {Topoisomerase II (Top2) is the essential protein that resolves DNA catenations. When Top2 is inactivated, mitotic catastrophe results from massive entanglement of chromosomes. Top2 is also the target of many first-line anticancer drugs, the so-called Top2 poisons. Often, tumors become resistant to these drugs by acquiring hypomorphic mutations in the genes encoding Top2. Here, we have compared the cell cycle and nuclear segregation of two coisogenic Saccharomyces cerevisiae strains carrying top2 thermosensitive alleles that differ in their resistance to Top2 poisons: the broadly-used poison-sensitive top2-4 and the poison-resistant top2-5 Furthermore, we have performed genome-scale Synthetic Genetic Array (SGA) analyses for both alleles under permissive conditions, chronic sublethal Top2 downregulation and acute, yet transient, Top2 inactivation. We find that slowing down mitotic progression, especially at the time of execution of the Mitotic Exit Network (MEN), protects against Top2 deficiency. In all conditions, genetic protection was stronger in top2-5, and this correlated with cell biology experiments in this mutant whereby we observed destabilization of both chromatin and ultrafine anaphase bridges by execution of MEN and cytokinesis. Interestingly, whereas transient inactivation of the critical MEN driver Cdc15 partly suppressed top2-5 lethality, this was not the case when earlier steps within anaphase were disrupted; i.e., top2-5 cdc14-1 We discuss the basis of this difference and suggest that accelerated progression through mitosis may be a therapeutic strategy to hypersensitize cancer cells carrying hypomorphic mutations in TOP2.},
author = {Ramos-P{\'{e}}rez, Cristina and Ayra-Plasencia, Jessel and Matos-Perdomo, Emiliano and Lisby, Michael and Brown, Grant W. and Mach{\'{i}}n, F{\'{e}}lix},
doi = {10.1534/g3.117.300104},
isbn = {0000000310},
issn = {2160-1836},
journal = {G3{\&}{\#}58; Genes|Genomes|Genetics},
pages = {g3.300104.2017},
pmid = {28839115},
title = {{Genome-Scale Genetic Interactions and Cell Imaging Confirm Cytokinesis as Deleterious to Transient Topoisomerase II Deficiency in {\textless}i{\textgreater}Saccharomyces cerevisiae{\textless}/i{\textgreater}}},
url = {http://g3journal.org/lookup/doi/10.1534/g3.117.300104},
year = {2017}
}
@article{Zhou2017a,
author = {Zhou, Jin and Wu, Zhong and Wong, Gabrielle and Pectasides, Eirini and Nagaraja, Ankur and Stachler, Matthew and Zhang, Haikuo and Chen, Ting and Zhang, Haisheng and Liu, Jie Bin and Xu, Xinsen and Sicinska, Ewa and Sanchez-Vega, Francisco and Rustgi, Anil K and Diehl, J Alan and Wong, Kwok-Kin and Bass, Adam J},
journal = {Nature Communications},
month = {jan},
pages = {13897},
publisher = {The Author(s)},
title = {{CDK4/6 or MAPK blockade enhances efficacy of EGFR inhibition in oesophageal squamous cell carcinoma}},
url = {https://doi.org/10.1038/ncomms13897 http://10.0.4.14/ncomms13897 https://www.nature.com/articles/ncomms13897{\#}supplementary-information},
volume = {8},
year = {2017}
}
@article{Sales2012,
abstract = {BACKGROUND: Gene set analysis is moving towards considering pathway topology as a crucial feature. Pathway elements are complex entities such as protein complexes, gene family members and chemical compounds. The conversion of pathway topology to a gene/protein networks (where nodes are a simple element like a gene/protein) is a critical and challenging task that enables topology-based gene set analyses.Unfortunately, currently available R/Bioconductor packages provide pathway networks only from single databases. They do not propagate signals through chemical compounds and do not differentiate between complexes and gene families.RESULTS: Here we present graphite, a Bioconductor package addressing these issues. Pathway information from four different databases is interpreted following specific biologically-driven rules that allow the reconstruction of gene-gene networks taking into account protein complexes, gene families and sensibly removing chemical compounds from the final graphs. The resulting networks represent a uniform resource for pathway analyses. Indeed, graphite provides easy access to three recently proposed topological methods. The graphite package is available as part of the Bioconductor software suite.CONCLUSIONS: graphite is an innovative package able to gather and make easily available the contents of the four major pathway databases. In the field of topological analysis graphite acts as a provider of biological information by reducing the pathway complexity considering the biological meaning of the pathway elements},
author = {Sales, Gabriele and Calura, Enrica and Cavalieri, Duccio and Romualdi, Chiara},
doi = {10.1186/1471-2105-13-20},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Sales et al. - 2012 - Graphite - a Bioconductor package to convert pathway topology to gene network.pdf:pdf},
isbn = {1471-2105},
issn = {14712105},
journal = {BMC Bioinformatics},
pmid = {22292714},
title = {{Graphite - a Bioconductor package to convert pathway topology to gene network}},
year = {2012}
}
@article{Morris2013a,
abstract = {Mathematical models are useful tools for understanding protein signaling networks because they provide an integrated view of pharmacological and toxicological processes at the molecular level. Here we describe an approach previously introduced based on logic modeling to generate cell-specific, mechanistic and predictive models of signal transduction. Models are derived from a network encoding prior knowledge that is trained to signaling data, and can be either binary (based on Boolean logic) or quantitative (using a recently developed formalism, constrained fuzzy logic). The approach is implemented in the freely available tool CellNetOptimizer (CellNOpt). We explain the process CellNOpt uses to train a prior knowledge network to data and illustrate its application with a toy example as well as a realistic case describing signaling networks in the HepG2 liver cancer cell line.},
author = {Morris, Melody K. and Melas, Ioannis and Saez-Rodriguez, Julio},
doi = {10.1007/978-1-62703-059-5_8},
isbn = {9781627030588},
issn = {10643745},
journal = {Methods in Molecular Biology},
keywords = {Boolean logic,Cell-specificity,Fuzzy logic,Logic model,Protein networks,Signal transduction},
pmid = {23086842},
title = {{Construction of cell type-specific logic models of signaling networks using CellNOpt}},
year = {2013}
}
@article{Alepuz2001,
abstract = {In response to hyperosmotic environments, most eukaryotic cells activate a specialized mitogen-activated protein (MAP) kinase pathway. In S. cerevisiae, the key protein kinase, Hog1, coordinates the transcriptional induction of a variety of genes devoted to osmoadaptation and general stress protection. Depending on the promoter context, Hog1 can function through a variety of structurally unrelated transcription factors. Using chromatin precipitation assays, we discovered that the kinase itself becomes intimately linked with promoter regions during stress responses. This interaction is dependent on the presence of stress-mediating transcriptional activators. In turn, Hog1 modulates promoter association of at least one of these factors. Additional findings highlight the possibility that Hog1 constitutes an integral part of the upstream activation complex, perhaps targeting not only the activator but also components of the general transcription machinery.},
author = {Alepuz, Paula M. and Jovanovic, Aleksandra and Reiser, Vladimir and Ammerer, Gustav},
doi = {10.1016/S1097-2765(01)00221-0},
issn = {10972765},
journal = {Molecular Cell},
number = {4},
pages = {767--777},
pmid = {11336700},
title = {{Stress-induced MAP kinase Hog1 is part of transcription activation complexes}},
volume = {7},
year = {2001}
}
@misc{Wilusz2013,
abstract = {The bacterial Hfq protein is a versatile modulator of RNA function and is particularly important for regulation mediated by small non-coding RNAs. Hfq is a bacterial Sm protein but bears more similarity to the eukaryotic Sm-like (Lsm) family of proteins than the prototypical Sm proteins. Hfq and Lsm proteins share the ability to chaperone RNA-RNA and RNA/protein interactions and an interesting penchant for protecting the 3' end of a transcript from exonucleolytic decay while encouraging degradation through other pathways. Our view of Lsm function in eukaryotes has historically been informed by studies of Hfq structure and function but mutational analyses and structural studies of Lsm sub-complexes have given important insights as well. Here, we aim to compare and contrast the roles of these evolutionarily related complexes and to highlight areas for future investigation.},
author = {Wilusz, Carol J. and Wilusz, Jeffrey},
booktitle = {RNA Biology},
doi = {10.4161/rna.23695},
isbn = {1555-8584 (Electronic)$\backslash$r1547-6286 (Linking)},
issn = {15558584},
keywords = {Exoribonuclease,Oligouridylation,Polyadenylation,RNA chaperone,Sm-like,Splicing,mRNA decay},
number = {4},
pages = {592--601},
pmid = {23392247},
title = {{Lsm proteins and Hfq: Life at the 3′ end}},
volume = {10},
year = {2013}
}
@article{Zanudo2013,
abstract = {Discrete dynamic models are a powerful tool for the understanding and modeling of large biological networks. Although a lot of progress has been made in developing analysis tools for these models, there is still a need to find approaches that can directly relate the network structure to its dynamics. Of special interest is identifying the stable patterns of activity, i.e., the attractors of the system. This is a problem for large networks, because the state space of the system increases exponentially with network size. In this work we present a novel network reduction approach that is based on finding network motifs that stabilize in a fixed state. Notably, we use a topological criterion to identify these motifs. Specifically, we find certain types of strongly connected components in a suitably expanded representation of the network. To test our method we apply it to a dynamic network model for a type of cytotoxic T cell cancer and to an ensemble of random Boolean networks of size up to 200. Our results show that our method goes beyond reducing the network and in most cases can actually predict the dynamical repertoire of the nodes (fixed states or oscillations) in the attractors of the system.},
archivePrefix = {arXiv},
arxivId = {1304.3467},
author = {Za{\~{n}}udo, Jorge G.T. and Albert, R{\'{e}}ka},
doi = {10.1063/1.4809777},
eprint = {1304.3467},
isbn = {1089-7682 (Electronic)$\backslash$r1054-1500 (Linking)},
issn = {10541500},
journal = {Chaos},
pmid = {23822509},
title = {{An effective network reduction approach to find the dynamical repertoire of discrete dynamic networks}},
year = {2013}
}
@article{Sato2000,
abstract = {BACKGROUND: Shc is the adaptor protein that exists in three isoforms, P46, P52 and P66, and acts as a bridge between activated cell surface receptors and downstream signalling molecules which act in extracellular signal-regulated cell events such as cell cycle progression. In our previous studies, Shc was shown to be a substrate of the tyrosine kinase c-Src in vitro and in vivo.$\backslash$n$\backslash$nRESULTS: Using green fluorescent protein-fusion Shc (GFP-Shc), we have shown that following epidermal growth factor (EGF) stimulation of A431 cells, all Shc isoforms were rapidly recruited from the cytoplasm to the plasma membrane (within 5 min) and then redistributed to the cytoplasmic vesicle structures (in the next 10-20 min). Indirect immunofluorescent study demonstrated that all Shc isoforms co-localize with EGF receptor (EGFR) and activated c-Src in both plasma membranes and cytoplasmic vesicle structures. Our previous study has shown that EGF induces the indirect association of EGFR and c-Src and activation of c-Src in A431 cells. An immunoprecipitation study demonstrated that the EGFR-Src association and c-Src activation are augmented in cells expressing GFP-Shc P52 or P66, but not P46. In addition, P52 and P66, but not P46, are in association with EGFR-Src complex. We also found that EGFR and Shc can be dissociated from c-Src by the addition of a synthetic peptide that corresponds to the autophosphorylation site of c-Src. Interestingly, the peptide-induced dissociation of the complex was not affected by the tyrosine phosphorylation state of the peptide.$\backslash$n$\backslash$nCONCLUSION: These results demonstrated a dynamic subcellular movement of Shc in response to EGF, and suggested a hitherto unknown scheme whereby Shc can work not only as a substrate of c-Src but also as a mediator of the EGF-induced activation of c-Src in an isoform-specific manner.},
author = {Sato, Ken Ichi and Kimoto, Miwa and Kakumoto, Miki and Horiuchi, Dai and Iwasaki, Tetsushi and Tokmakov, Alexander A. and Fukami, Yasuo},
doi = {10.1046/j.1365-2443.2000.00358.x},
isbn = {1356-9597},
issn = {13569597},
journal = {Genes to Cells},
pmid = {10971656},
title = {{Adaptor protein Shc undergoes translocation and mediates up-regulation of the tyrosine kinase c-Src in EGF-stimulated A431 cells}},
year = {2000}
}
@misc{Shaw2006,
abstract = {All eukaryotic cells coordinate cell growth with the availability of nutrients in their environment. The mTOR protein kinase has emerged as a critical growth-control node, receiving stimulatory signals from Ras and phosphatidylinositol-3-OH kinase (PI(3)K) downstream from growth factors, as well as nutrient inputs in the form of amino-acid, glucose and oxygen availability. Notably, components of the Ras and PI(3)K signalling pathways are mutated in most human cancers. The preponderance of mutations in these interconnected pathways suggests that the loss of growth-control checkpoints and promotion of cell survival in nutrient-limited conditions may be an obligate event in tumorigenesis.},
author = {Shaw, Reuben J. and Cantley, Lewis C.},
booktitle = {Nature},
doi = {10.1038/nature04869},
isbn = {1476-4687 (Electronic)},
issn = {14764687},
pmid = {16724053},
title = {{Ras, PI(3)K and mTOR signalling controls tumour cell growth}},
year = {2006}
}
@misc{Irwin2012,
abstract = {ZINC is a free public resource for ligand discovery. The database contains over twenty million commercially available molecules in biologically relevant representations that may be downloaded in popular ready-to-dock formats and subsets. The Web site also enables searches by structure, biological activity, physical property, vendor, catalog number, name, and CAS number. Small custom subsets may be created, edited, shared, docked, downloaded, and conveyed to a vendor for purchase. The database is maintained and curated for a high purchasing success rate and is freely available at zinc.docking.org.},
author = {Irwin, John J. and Sterling, Teague and Mysinger, Michael M. and Bolstad, Erin S. and Coleman, Ryan G.},
booktitle = {Journal of Chemical Information and Modeling},
doi = {10.1021/ci3001277},
isbn = {1549-960X (Electronic)$\backslash$r1549-9596 (Linking)},
issn = {15499596},
number = {7},
pages = {1757--1768},
pmid = {22587354},
title = {{ZINC: A free tool to discover chemistry for biology}},
volume = {52},
year = {2012}
}
@article{Wang2013,
abstract = {Mice carrying mutations in multiple genes are tradi- tionally generated by sequential recombination in embryonic stem cells and/or time-consuming inter- crossing of mice with a single mutation. The CRISPR/Cas system has been adapted as an effi- cient gene-targeting technology with the potential for multiplexed genome editing. We demonstrate that CRISPR/Cas-mediated gene editing allows the simultaneous disruption of five genes (Tet1, 2, 3, Sry, Uty - 8 alleles) in mouse embryonic stem (ES) cells with high efficiency. Coinjection of Cas9 mRNA and single-guide RNAs (sgRNAs) targeting Tet1 and Tet2 into zygotes generated mice with bial- lelic mutations in both genes with an efficiency of 80{\%}. Finally, we show that coinjection of Cas9 mRNA/sgRNAs with mutant oligos generated pre- cise point mutations simultaneously in two target genes. Thus, the CRISPR/Cas system allows the one-step generation of animals carrying mutations in multiple genes, an approach that will greatly accel- erate the in vivo study of functionally redundant genes and of epistatic gene interactions.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Wang, Haoyi and Yang, Hui and Shivalila, CS},
doi = {10.1016/j.cell.2013.04.025},
eprint = {NIHMS150003},
isbn = {1097-4172 (Electronic)$\backslash$n0092-8674 (Linking)},
issn = {0092-8674},
journal = {Cell},
pages = {1--9},
pmid = {23643243},
title = {{One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR / Cas-Mediated Genome Engineering}},
url = {http://www.sciencedirect.com/science/article/pii/S0092867413004674},
volume = {153},
year = {2013}
}
@article{Kleinstiver2015,
abstract = {Although {\{}CRISPR-Cas9{\}} nucleases are widely used for genome editing, the range of sequences that Cas9 can recognize is constrained by the need for a specific protospacer adjacent motif {\{}(PAM).{\}} As a result, it can often be difficult to target double-stranded breaks {\{}(DSBs){\}} with the precision that is necessary for various genome-editing applications. The ability to engineer Cas9 derivatives with purposefully altered {\{}PAM{\}} specificities would address this limitation. Here we show that the commonly used Streptococcus pyogenes Cas9 {\{}(SpCas9){\}} can be modified to recognize alternative {\{}PAM{\}} sequences using structural information, bacterial selection-based directed evolution, and combinatorial design. These altered {\{}PAM{\}} specificity variants enable robust editing of endogenous gene sites in zebrafish and human cells not currently targetable by wild-type {\{}SpCas9,{\}} and their genome-wide specificities are comparable to wild-type {\{}SpCas9{\}} as judged by {\{}GUIDE-seq{\}} analysis. In addition, we identify and characterize another {\{}SpCas9{\}} variant that exhibits improved specificity in human cells, possessing better discrimination against off-target sites with non-canonical {\{}NAG{\}} and {\{}NGA{\}} {\{}PAMs{\}} and/or mismatched spacers. We also find that two smaller-size Cas9 orthologues, Streptococcus thermophilus Cas9 {\{}(St1Cas9){\}} and Staphylococcus aureus Cas9 {\{}(SaCas9),{\}} function efficiently in the bacterial selection systems and in human cells, suggesting that our engineering strategies could be extended to Cas9s from other species. Our findings provide broadly useful {\{}SpCas9{\}} variants and, more importantly, establish the feasibility of engineering a wide range of Cas9s with altered and improved {\{}PAM{\}} specificities.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Kleinstiver, Benjamin P. and Prew, Michelle S. and Tsai, Shengdar Q. and Topkar, Ved V. and Nguyen, Nhu T. and Zheng, Zongli and Gonzales, Andrew P. W. and Li, Zhuyun and Peterson, Randall T. and Yeh, Jing-Ruey Joanna and Aryee, Martin J. and Joung, J. Keith},
doi = {10.1038/nature14592},
eprint = {NIHMS150003},
isbn = {1476-4687 (Electronic)$\backslash$r0028-0836 (Linking)},
issn = {0028-0836},
journal = {Nature},
number = {7561},
pages = {481--485},
pmid = {26098369},
title = {{Engineered CRISPR-Cas9 nucleases with altered PAM specificities}},
url = {http://www.nature.com/doifinder/10.1038/nature14592},
volume = {523},
year = {2015}
}
@article{Jakocinas2015,
abstract = {{\textcopyright} 2015 International Metabolic Engineering Society. CRISPR/Cas9 is a simple and efficient tool for targeted and marker-free genome engineering. Here, we report the development and successful application of a multiplex CRISPR/Cas9 system for genome engineering of up to 5 different genomic loci in one transformation step in baker's yeast Saccharomyces cerevisiae. To assess the specificity of the tool we employed genome re-sequencing to screen for off-target sites in all single knock-out strains targeted by different gRNAs. This extensive analysis identified no more genome variants in CRISPR/Cas9 engineered strains compared to wild-type reference strains. We applied our genome engineering tool for an exploratory analysis of all possible single, double, triple, quadruple and quintuple gene disruption combinations to search for strains with high mevalonate production, a key intermediate for the industrially important isoprenoid biosynthesis pathway. Even though we did not overexpress any genes in the mevalonate pathway, this analysis identified strains with mevalonate titers greater than 41-fold compared to the wild-type strain. Our findings illustrate the applicability of this highly specific and efficient multiplex genome engineering approach to accelerate functional genomics and metabolic engineering efforts.},
author = {Jako{\v{c}}inas, T. and Bonde, I. and Herrg{\aa}rd, M. and Harrison, S.J. and Kristensen, M. and Pedersen, L.E. and Jensen, M.K. and Keasling, J.D.},
doi = {10.1016/j.ymben.2015.01.008},
issn = {10967184 10967176},
journal = {Metabolic Engineering},
keywords = {CRISPR/Cas9,Mevalonate,Multiplex genome editing,Off-target analysis,Yeast},
pages = {213--222},
title = {{Multiplex metabolic pathway engineering using CRISPR/Cas9 in Saccharomyces cerevisiae}},
volume = {28},
year = {2015}
}
@article{Mendes2014,
abstract = {Motivation: Models of discrete concurrent systems often lead to huge and complex state transition graphs that represent their dynamics. This makes difficult to analyse dynamical properties. In particular, for logical models of biological regulatory networks, it is of real interest to study attractors and their reachability from specific initial conditions, i.e. to assess the potential asymptotical behaviours of the system. Beyond the identification of the reachable attractors, we propose to quantify this reachability. Results: Relying on the structure of the state transition graph, we estimate the probability of each attractor reachable from a given initial condition or from a portion of the state space. First, we present a quasi-exact solution with an original algorithm called Firefront, based on the exhaustive exploration of the reachable state space. Then, we introduce an adapted version of Monte Carlo simulation algorithm, termed Avatar, better suited to larger models. Firefront and Avatar methods are validated and compared to other related approaches, using as test cases logical models of synthetic and biological networks. Availability: Both algorithms are implemented as Perl scripts that can be freely downloaded from http://compbio.igc.gulbenkian.pt/nmd/node/59 along with Supplementary Material.},
archivePrefix = {arXiv},
arxivId = {1411.3539},
author = {Mendes, Nuno D. and Monteiro, Pedro T. and Carneiro, Jorge and Remy, Elisabeth and Chaouiya, Claudine},
eprint = {1411.3539},
file = {:Users/ozlem/Desktop/Tools/1411.3539.pdf:pdf},
pages = {1--19},
title = {{Quantification of reachable attractors in asynchronous discrete dynamics}},
url = {http://arxiv.org/abs/1411.3539},
year = {2014}
}
@article{Kholodenko1999,
abstract = {Wnts are a large family of secreted glycoproteins that mediate bone development in the embryo and promote bone production in the adult. Autocrine Wnt signaling within tumor cells has been shown to promote tumorigenesis by enhancing tumor cell proliferation and survival. We recently demonstrated that prostate cancer cells (CaP) produce Wnts which act in a paracrine fashion to induce osteoblastic activity in CaP bone metastases. The ability of tumor-derived Wnts to influence bone development is regulated by multiple families of secreted antagonists including soluble frizzled related receptors (sFrp) and dickkopfs (DKK). CaP cells appear to produce DKK-1 early in the development of skeletal metastases, which masks osteogenic Wnts and thus favors an osteolytic environment at the metastatic site. As the metastases progresses, DKK-1 expression is lost allowing for a Wnt mediated osteoblastic response which predominates CaP boney lesions. Interestingly, blocking DKK-1 expression early in CaP metastasis prevents tumor establishment within the bone suggesting that osteolysis is a required first step in the development of CaP bone metastases. In this review, we discuss our data on the Wnt inhibitor DKK-1 in CaP bone metastasis in the context of current literature evidence that demonstrate that Wnt inhibitors can function as both tumor suppressors and tumor promoters. We provide a model that the affect of Wnt inhibitors on tumor development is dependent on the tumor micro-environment and suggest that DKK-1 is a switch which transitions CaP bone metastases from osteolytic to osteoblastic.},
author = {Kholodenko, Boris N. and Demin, Oleg V. and Moehren, Gisela and Hoek, Jan B.},
doi = {10.1074/jbc.274.42.30169},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Kholodenko et al. - 1999 - Quantification of short term signaling by the epidermal growth factor receptor.pdf:pdf},
isbn = {0021-9258 (Print)$\backslash$n0021-9258 (Linking)},
issn = {00219258},
journal = {Journal of Biological Chemistry},
number = {42},
pages = {30169--30181},
pmid = {10514507},
title = {{Quantification of short term signaling by the epidermal growth factor receptor}},
volume = {274},
year = {1999}
}
@misc{Bonneau2008,
abstract = {Learning regulatory networks from genomics data is an important problem with applications spanning all of biology and biomedicine. Functional genomics projects offer a cost- effective means of greatly expanding the completeness of our regulatory models, and for some prokaryotic organisms they offer a means of learning accurate models that incorporate the majority of the genome. There are, however, several reasons to believe that regulatory network inference is beyond our current reach, such as (i) the combinatorics of the problem, (ii) factors we can't (or don't often) collect genome-wide measurements for and (iii) dynamics that elude cost-effective experimental designs. Recent works have demonstrated the ability to reconstruct large fractions of prokaryotic regulatory networks from compendiums of genomics data; they have also demonstrated that these global regulatory models can be used to predict the dynamics of the transcriptome. We review an overall strategy for the reconstruction of global networks based on these results in microbial systems.},
author = {Bonneau, Richard},
booktitle = {Nature Chemical Biology},
doi = {10.1038/nchembio.122},
isbn = {1552-4469 (Electronic)},
issn = {15524469},
pmid = {18936750},
title = {{Learning biological networks: From modules to dynamics}},
year = {2008}
}
@incollection{Villoutreix2016,
author = {Villoutreix, BO},
booktitle = {In silico Drug Design: some concepts {\&} tools},
pages = {7--15},
title = {{Comments about virtual ligand screening and drug design}},
year = {2016}
}
@article{Cobrinik2005,
author = {Cobrinik, David},
journal = {Oncogene},
month = {apr},
pages = {2796},
publisher = {Nature Publishing Group},
title = {{Pocket proteins and cell cycle control}},
url = {https://doi.org/10.1038/sj.onc.1208619 http://10.0.4.14/sj.onc.1208619},
volume = {24},
year = {2005}
}
@misc{Cvijovic2014,
abstract = {Systems biology aims at creating mathematical models, i.e., computational reconstructions of biological systems and processes that will result in a new level of understanding-the elucidation of the basic and presumably conserved "design" and "engineering" principles of biomolecular systems. Thus, systems biology will move biology from a phenomenological to a predictive science. Mathematical modeling of biological networks and processes has already greatly improved our understanding of many cellular processes. However, given the massive amount of qualitative and quantitative data currently produced and number of burning questions in health care and biotechnology needed to be solved is still in its early phases. The field requires novel approaches for abstraction, for modeling bioprocesses that follow different biochemical and biophysical rules, and for combining different modules into larger models that still allow realistic simulation with the computational power available today. We have identified and discussed currently most prominent problems in systems biology: (1) how to bridge different scales of modeling abstraction, (2) how to bridge the gap between topological and mechanistic modeling, and (3) how to bridge the wet and dry laboratory gap. The future success of systems biology largely depends on bridging the recognized gaps.},
author = {Cvijovic, Marija and Almquist, Joachim and Hagmar, Jonas and Hohmann, Stefan and Kaltenbach, Hans Michael and Klipp, Edda and Krantz, Marcus and Mendes, Pedro and Nelander, Sven and Nielsen, Jens and Pagnani, Andrea and Przulj, Natasa and Raue, Andreas and Stelling, J{\"{o}}rg and Stoma, Szymon and Tobin, Frank and Wodke, Judith A.H. and Zecchina, Riccardo and Jirstrand, Mats},
booktitle = {Molecular genetics and genomics : MGG},
doi = {10.1007/s00438-014-0843-3},
issn = {16174623},
pmid = {24728588},
title = {{Bridging the gaps in systems biology.}},
year = {2014}
}
@article{Measday2005,
abstract = {Accurate chromosome segregation requires the execution and coordination of many processes during mitosis, including DNA replication, sister chromatid cohesion, and attachment of chromosomes to spindle microtubules via the kinetochore complex. Additional pathways are likely involved because faithful chromosome segregation also requires proteins that are not physically associated with the chromosome. Using kinetochore mutants as a starting point, we have identified genes with roles in chromosome stability by performing genome-wide screens employing synthetic genetic array methodology. Two genetic approaches (a series of synthetic lethal and synthetic dosage lethal screens) isolated 211 nonessential deletion mutants that were unable to tolerate defects in kinetochore function. Although synthetic lethality and synthetic dosage lethality are thought to be based upon similar genetic principles, we found that the majority of interactions associated with these two screens were nonoverlapping. To functionally characterize genes isolated in our screens, a secondary screen was performed to assess defects in chromosome segregation. Genes identified in the secondary screen were enriched for genes with known roles in chromosome segregation. We also uncovered genes with diverse functions, such as RCS1, which encodes an iron transcription factor. RCS1 was one of a small group of genes identified in all three screens, and we used genetic and cell biological assays to confirm that it is required for chromosome stability. Our study shows that systematic genetic screens are a powerful means to discover roles for uncharacterized genes and genes with alternative functions in chromosome maintenance that may not be discovered by using proteomics approaches.},
author = {Measday, V. and Baetz, K. and Guzzo, J. and Yuen, K. and Kwok, T. and Sheikh, B. and Ding, H. and Ueta, R. and Hoac, T. and Cheng, B. and Pot, I. and Tong, A. and Yamaguchi-Iwai, Y. and Boone, C. and Hieter, P. and Andrews, B.},
doi = {10.1073/pnas.0503504102},
isbn = {0027-8424 (Print)$\backslash$r0027-8424 (Linking)},
issn = {0027-8424},
journal = {Proceedings of the National Academy of Sciences},
number = {39},
pages = {13956--13961},
pmid = {16172405},
title = {{Systematic yeast synthetic lethal and synthetic dosage lethal screens identify genes required for chromosome segregation}},
url = {http://www.pnas.org/cgi/doi/10.1073/pnas.0503504102},
volume = {102},
year = {2005}
}
@article{Yu2011,
abstract = {The evolutionarily conserved serine-threonine kinase mammalian target of rapamycin (mTOR) plays a critical role in regulating many pathophysiological processes. Functional characterization of the mTOR signaling pathways, however, has been hampered by the paucity of known substrates. We used large-scale quantitative phosphoproteomics experiments to define the signaling networks downstream of mTORC1 and mTORC2. Characterization of one mTORC1 substrate, the growth factor receptor-bound protein 10 (Grb10), showed that mTORC1-mediated phosphorylation stabilized Grb10, leading to feedback inhibition of the phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated, mitogen-activated protein kinase (ERK-MAPK) pathways. Grb10 expression is frequently down-regulated in various cancers, and loss of Grb10 and loss of the well-established tumor suppressor phosphatase PTEN appear to be mutually exclusive events, suggesting that Grb10 might be a tumor suppressor regulated by mTORC1.},
archivePrefix = {arXiv},
arxivId = {arXiv:1011.1669v3},
author = {Yu, Yonghao and Yoon, Sang Oh and Poulogiannis, George and Yang, Qian and Ma, Xiaoju Max and Vill{\'{e}}n, Judit and Kubica, Neil and Hoffman, Gregory R. and Cantley, Lewis C. and Gygi, Steven P. and Blenis, John},
doi = {10.1126/science.1199484},
eprint = {arXiv:1011.1669v3},
isbn = {9788578110796},
issn = {00368075},
journal = {Science},
pmid = {21659605},
title = {{Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling}},
year = {2011}
}
@article{Wrzodek2013b,
abstract = {BACKGROUND: The KEGG PATHWAY database provides a plethora of pathways for a diversity of organisms. All pathway components are directly linked to other KEGG databases, such as KEGG COMPOUND or KEGG REACTION. Therefore, the pathways can be extended with an enormous amount of information and provide a foundation for initial structural modeling approaches. As a drawback, KGML-formatted KEGG pathways are primarily designed for visualization purposes and often omit important details for the sake of a clear arrangement of its entries. Thus, a direct conversion into systems biology models would produce incomplete and erroneous models.$\backslash$n$\backslash$nRESULTS: Here, we present a precise method for processing and converting KEGG pathways into initial metabolic and signaling models encoded in the standardized community pathway formats SBML (Levels 2 and 3) and BioPAX (Levels 2 and 3). This method involves correcting invalid or incomplete KGML content, creating complete and valid stoichiometric reactions, translating relations to signaling models and augmenting the pathway content with various information, such as cross-references to Entrez Gene, OMIM, UniProt ChEBI, and many more.Finally, we compare several existing conversion tools for KEGG pathways and show that the conversion from KEGG to BioPAX does not involve a loss of information, whilst lossless translations to SBML can only be performed using SBML Level 3, including its recently proposed qualitative models and groups extension packages.$\backslash$n$\backslash$nCONCLUSIONS: Building correct BioPAX and SBML signaling models from the KEGG database is a unique characteristic of the proposed method. Further, there is no other approach that is able to appropriately construct metabolic models from KEGG pathways, including correct reactions with stoichiometry. The resulting initial models, which contain valid and comprehensive SBML or BioPAX code and a multitude of cross-references, lay the foundation to facilitate further modeling steps.},
author = {Wrzodek, Clemens and B{\"{u}}chel, Finja and Ruff, Manuel and Dr{\"{a}}ger, Andreas and Zell, Andreas},
doi = {10.1186/1752-0509-7-15},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Wrzodek et al. - 2013 - Precise generation of systems biology models from KEGG pathways(2).pdf:pdf},
isbn = {1752-0509 (Electronic)$\backslash$r1752-0509 (Linking)},
issn = {17520509},
journal = {BMC Systems Biology},
keywords = {BioPAX,Comparison,Converter,KEGG,KGML,Modeling,Qualitative modeling,Quantitative modeling,SBML,Systems biology},
pmid = {23433509},
title = {{Precise generation of systems biology models from KEGG pathways}},
year = {2013}
}
@misc{Irwin2012a,
abstract = {ZINC is a free public resource for ligand discovery. The database contains over twenty million commercially available molecules in biologically relevant representations that may be downloaded in popular ready-to-dock formats and subsets. The Web site also enables searches by structure, biological activity, physical property, vendor, catalog number, name, and CAS number. Small custom subsets may be created, edited, shared, docked, downloaded, and conveyed to a vendor for purchase. The database is maintained and curated for a high purchasing success rate and is freely available at zinc.docking.org.},
author = {Irwin, John J. and Sterling, Teague and Mysinger, Michael M. and Bolstad, Erin S. and Coleman, Ryan G.},
booktitle = {Journal of Chemical Information and Modeling},
doi = {10.1021/ci3001277},
isbn = {1549-960X (Electronic)$\backslash$r1549-9596 (Linking)},
issn = {15499596},
number = {7},
pages = {1757--1768},
pmid = {22587354},
title = {{ZINC: A free tool to discover chemistry for biology}},
volume = {52},
year = {2012}
}
@article{Schmidt2002,
abstract = {The FoxO forkhead transcription factors FoxO4 (AFX), FoxO3a (FKHR.L1), and FoxO1a (FKHR) represent important physiological targets of phosphatidylinositol-3 kinase (PI3K)/protein kinase B (PKB) signaling. Overexpression or conditional activation of FoxO factors is able to antagonize many responses to constitutive PI3K/PKB activation including its effect on cellular proliferation. It was previously shown that the FoxO-induced cell cycle arrest is partially mediated by enhanced transcription and protein expression of the cyclin-dependent kinase inhibitor p27kip1 (R. H. Medema, G. J. Kops, J. L. Bos, and B. M. Burgering, Nature 404:782-787, 2000). Here we have identified a p27kip1-independent mechanism that plays an important role in the antiproliferative effect of FoxO factors. Forced expression or conditional activation of FoxO factors leads to reduced protein expression of the D-type cyclins D1 and D2 and is associated with an impaired capacity of CDK4 to phosphorylate and inactivate the S-phase repressor pRb. Downregulation of D-type cyclins involves a transcriptional repression mechanism and does not require p27kip1 function. Ectopic expression of cyclin D1 can partially overcome FoxO factor-induced cell cycle arrest, demonstrating that downregulation of D-type cyclins represents a physiologically relevant mechanism of FoxO-induced cell cycle inhibition.},
author = {Schmidt, Marc and {Fernandez de Mattos}, Sylvia and van der Horst, Armando and Klompmaker, Rob and Kops, Geert J P L and Lam, Eric W.-F. and Burgering, Boudewijn M T and Medema, Ren{\'{e}} H},
doi = {10.1128/MCB.22.22.7842-7852.2002},
journal = {Molecular and Cellular Biology},
month = {nov},
number = {22},
pages = {7842 LP  -- 7852},
title = {{Cell Cycle Inhibition by FoxO Forkhead Transcription Factors Involves Downregulation of Cyclin D}},
url = {http://mcb.asm.org/content/22/22/7842.abstract},
volume = {22},
year = {2002}
}
@article{Slaymaker2016,
abstract = {The RNA-guided endonuclease Cas9 is a versatile genome editing tool with a broad range of applications from therapeutics to functional annotation of genes. Cas9 creates double-strand breaks (DSBs) at targeted genomic loci complementary to a short RNA guide. However, Cas9 can cleave off-target sites that are not fully complementary to the guide, which poses a major challenge for genome editing. Here, we use structure-guided protein engineering to improve the specificity of Streptococcus pyogenes Cas9 (SpCas9). Using targeted deep sequencing and unbiased whole-genome off-target analysis to assess Cas9-mediated DNA cleavage in human cells, we demonstrate that "enhanced specificity" SpCas9 (eSpCas9) variants reduce off-target effects and maintain robust on-target cleavage. Thus, eSpCas9 could be broadly useful for genome editing applications requiring a high level of specificity.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Slaymaker, I. M. and Gao, L. and Zetsche, B. and Scott, D. A. and Yan, W. X. and Zhang, F.},
doi = {10.1126/science.aad5227},
eprint = {NIHMS150003},
isbn = {1095-9203 (Electronic)$\backslash$r0036-8075 (Linking)},
issn = {0036-8075},
journal = {Science},
number = {6268},
pages = {84--88},
pmid = {23873081},
title = {{Rationally engineered Cas9 nucleases with improved specificity}},
url = {http://www.sciencemag.org/cgi/doi/10.1126/science.aad5227},
volume = {351},
year = {2016}
}
@article{Wang2012d,
abstract = {PubChem (http://pubchem.ncbi.nlm.nih.gov) is a public repository for biological activity data of small molecules and RNAi reagents. The mission of PubChem is to deliver free and easy access to all deposited data, and to provide intuitive data analysis tools. The PubChem BioAssay database currently contains 500,000 descriptions of assay protocols, covering 5000 protein targets, 30,000 gene targets and providing over 130 million bioactivity outcomes. PubChem's bioassay data are integrated into the NCBI Entrez information retrieval system, thus making PubChem data searchable and accessible by Entrez queries. Also, as a repository, PubChem constantly optimizes and develops its deposition system answering many demands of both high- and low-volume depositors. The PubChem information platform allows users to search, review and download bioassay description and data. The PubChem platform also enables researchers to collect, compare and analyze biological test results through web-based and programmatic tools. In this work, we provide an update for the PubChem BioAssay resource, including information content growth, data model extension and new developments of data submission, retrieval, analysis and download tools.},
author = {Wang, Yanli and Xiao, Jewen and Suzek, Tugba O. and Zhang, Jian and Wang, Jiyao and Zhou, Zhigang and Han, Lianyi and Karapetyan, Karen and Dracheva, Svetlana and Shoemaker, Benjamin A. and Bolton, Evan and Gindulyte, Asta and Bryant, Stephen H.},
doi = {10.1093/nar/gkr1132},
isbn = {1362-4962 (Linking)},
issn = {03051048},
journal = {Nucleic Acids Research},
number = {D1},
pmid = {22140110},
title = {{PubChem's BioAssay database}},
volume = {40},
year = {2012}
}
@article{Margolin2006a,
abstract = {We describe a computational protocol for the ARACNE algorithm, an information-theoretic method for identifying transcriptional interactions between gene products using microarray expression profile data. Similar to other algorithms, ARACNE predicts potential functional associations among genes, or novel functions for uncharacterized genes, by identifying statistical dependencies between gene products. However, based on biochemical validation, literature searches and DNA binding site enrichment analysis, ARACNE has also proven effective in identifying bona fide transcriptional targets, even in complex mammalian networks. Thus we envision that predictions made by ARACNE, especially when supplemented with prior knowledge or additional data sources, can provide appropriate hypotheses for the further investigation of cellular networks. While the examples in this protocol use only gene expression profile data, the algorithm's theoretical basis readily extends to a variety of other high-throughput measurements, such as pathway-specific or genome-wide proteomics, microRNA and metabolomics data. As these data become readily available, we expect that ARACNE might prove increasingly useful in elucidating the underlying interaction models. For a microarray data set containing approximately 10,000 probes, reconstructing the network around a single probe completes in several minutes using a desktop computer with a Pentium 4 processor. Reconstructing a genome-wide network generally requires a computational cluster, especially if the recommended bootstrapping procedure is used.},
author = {Margolin, Adam A. and Wang, Kai and Lim, Wei Keat and Kustagi, Manjunath and Nemenman, Ilya and Califano, Andrea},
doi = {10.1038/nprot.2006.106},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Margolin et al. - 2006 - Reverse engineering cellular networks(2).pdf:pdf},
isbn = {1750-2799 (Electronic)},
issn = {17542189},
journal = {Nature Protocols},
number = {2},
pages = {662--671},
pmid = {17406294},
title = {{Reverse engineering cellular networks}},
volume = {1},
year = {2006}
}
@article{Sato2000a,
abstract = {BACKGROUND: Shc is the adaptor protein that exists in three isoforms, P46, P52 and P66, and acts as a bridge between activated cell surface receptors and downstream signalling molecules which act in extracellular signal-regulated cell events such as cell cycle progression. In our previous studies, Shc was shown to be a substrate of the tyrosine kinase c-Src in vitro and in vivo.$\backslash$n$\backslash$nRESULTS: Using green fluorescent protein-fusion Shc (GFP-Shc), we have shown that following epidermal growth factor (EGF) stimulation of A431 cells, all Shc isoforms were rapidly recruited from the cytoplasm to the plasma membrane (within 5 min) and then redistributed to the cytoplasmic vesicle structures (in the next 10-20 min). Indirect immunofluorescent study demonstrated that all Shc isoforms co-localize with EGF receptor (EGFR) and activated c-Src in both plasma membranes and cytoplasmic vesicle structures. Our previous study has shown that EGF induces the indirect association of EGFR and c-Src and activation of c-Src in A431 cells. An immunoprecipitation study demonstrated that the EGFR-Src association and c-Src activation are augmented in cells expressing GFP-Shc P52 or P66, but not P46. In addition, P52 and P66, but not P46, are in association with EGFR-Src complex. We also found that EGFR and Shc can be dissociated from c-Src by the addition of a synthetic peptide that corresponds to the autophosphorylation site of c-Src. Interestingly, the peptide-induced dissociation of the complex was not affected by the tyrosine phosphorylation state of the peptide.$\backslash$n$\backslash$nCONCLUSION: These results demonstrated a dynamic subcellular movement of Shc in response to EGF, and suggested a hitherto unknown scheme whereby Shc can work not only as a substrate of c-Src but also as a mediator of the EGF-induced activation of c-Src in an isoform-specific manner.},
author = {Sato, Ken Ichi and Kimoto, Miwa and Kakumoto, Miki and Horiuchi, Dai and Iwasaki, Tetsushi and Tokmakov, Alexander A. and Fukami, Yasuo},
doi = {10.1046/j.1365-2443.2000.00358.x},
isbn = {1356-9597},
issn = {13569597},
journal = {Genes to Cells},
pmid = {10971656},
title = {{Adaptor protein Shc undergoes translocation and mediates up-regulation of the tyrosine kinase c-Src in EGF-stimulated A431 cells}},
year = {2000}
}
@article{Buzko2002,
abstract = {Protein kinases are an important class of enzymes controlling virtually all cellular signaling pathways. Consequently, selective inhibitors of protein kinases have attracted significant interest as potential new drugs for many diseases. Computational methods, including molecular docking, have increasingly been used in the inhibitor design process [1]. We have considered several docking packages in order to strengthen our kinase inhibitor work with computational capabilities. In our experience, AutoDock offered a reasonable combination of accuracy and speed, as opposed to methods that specialize either in fast database searches or detailed and computationally intensive calculations. However, AutoDock did not perform well in cases where extensive hydrophobic contacts were involved, such as docking of SB203580 to its target protein kinase p38. Another shortcoming was a hydrogen bonding energy function, which underestimated the attraction component and, thus, did not allow for sufficiently accurate modeling of the key hydrogen bonds in the kinase-inhibitor complexes. We have modified the parameter set used to model hydrogen bonds, which increased the accuracy of AutoDock and appeared to be generally applicable to many kinase-inhibitor pairs without customization. Binding to largely hydrophobic sites, such as the active site of p38, was significantly improved by introducing a correction factor selectively affecting only carbon and hydrogen energy grids, thus, providing an effective, although approximate, treatment of solvation.},
author = {Buzko, Oleksandr V. and Bishop, Anthony C. and Shokat, Kevan M.},
doi = {10.1023/A:1016366013656},
isbn = {0920-654X (Print)$\backslash$n0920-654X (Linking)},
issn = {0920654X},
journal = {Journal of Computer-Aided Molecular Design},
keywords = {Approximation of solvation,AutoDock,Force field,Hydrogen bonding,Inhibitor design,Scoring function},
number = {2},
pages = {113--127},
pmid = {12188021},
title = {{Modified AutoDock for accurate docking of protein kinase inhibitors}},
volume = {16},
year = {2002}
}
@article{Kim1999,
annote = {doi: 10.1021/bi990579h},
author = {Kim, Yong and Han, Jung Min and Park, Jong Bae and Lee, Sang Do and Oh, Yong Seok and Chung, Churo and Lee, Taehoon G and Kim, Jae Ho and Park, Seung-Kiel and Yoo, Jong-Shin and Suh, Pann-Ghill and Ryu, Sung Ho},
doi = {10.1021/bi990579h},
issn = {0006-2960},
journal = {Biochemistry},
month = {aug},
number = {32},
pages = {10344--10351},
publisher = {American Chemical Society},
title = {{Phosphorylation and Activation of Phospholipase D1 by Protein Kinase C in Vivo:  Determination of Multiple Phosphorylation Sites}},
url = {https://doi.org/10.1021/bi990579h},
volume = {38},
year = {1999}
}
@article{Baryshnikova2010b,
abstract = {A genetic interaction occurs when the combination of two mutations leads to an unexpected phenotype. Screens for synthetic genetic interactions have been used extensively to identify genes whose products are functionally related. In particular, synthetic lethal genetic interactions often identify genes that buffer one another or impinge on the same essential pathway. For the yeast Saccharomyces cerevisiae, we developed a method termed synthetic genetic array (SGA) analysis, which offers an efficient approach for the systematic construction of double mutants and enables a global analysis of synthetic genetic interactions. In a typical SGA screen, a query mutation is crossed to an ordered array of ∼5000 viable gene deletion mutants (representing ∼80{\%} of all yeast genes) such that meiotic progeny harboring both mutations can be scored for fitness defects. This approach can be extended to all ∼6000 genes through the use of yeast arrays containing mutants carrying conditional or hypomorphic alleles of essential genes. Estimating the fitness for the two single mutants and their corresponding double mutant enables a quantitative measurement of genetic interactions, distinguishing negative (synthetic lethal) and positive (within pathway and suppression) interactions. The profile of genetic interactions represents a rich phenotypic signature for each gene and clustering genetic interaction profiles group genes into functionally relevant pathways and complexes. This array-based approach automates yeast genetic analysis in general and can be easily adapted for a number of different genetic screens or combined with high-content screening systems to quantify the activity of specific reporters in genome-wide sets of single or more complex multiple mutant backgrounds. Comparison of genetic and chemical-genetic interaction profiles offers the potential to link bioactive compounds to their targets. Finally, we also developed an SGA system for the fission yeast Schizosaccharomyces pombe, providing another model system for comparative analysis of genetic networks and testing the conservation of genetic networks over millions of years of evolution. {\textcopyright} 2010 Elsevier Inc. All rights reserved.},
author = {Baryshnikova, Anastasia and Costanzo, Michael and Dixon, Scott and Vizeacoumar, Franco J. and Myers, Chad L. and Andrews, Brenda and Boone, Charles},
doi = {10.1016/S0076-6879(10)70007-0},
isbn = {9780123751720},
issn = {00766879},
journal = {Methods in Enzymology},
number = {C},
pages = {145--179},
pmid = {20946810},
title = {{Synthetic genetic array (SGA) analysis in Saccharomyces cerevisiae and schizosaccharomyces pombe}},
volume = {470},
year = {2010}
}
@article{Anacker2018,
abstract = {Adult neurogenesis in the dentate gyrus of the hippocampus is highly regulated by environmental influences, and functionally implicated in behavioural responses to stress and antidepressants1–4. However, how adult-born neurons regulate dentate gyrus information processing to protect from stress-induced anxiety-like behaviour is unknown. Here we show in mice that neurogenesis confers resilience to chronic stress by inhibiting the activity of mature granule cells in the ventral dentate gyrus (vDG), a subregion that is implicated in mood regulation. We found that chemogenetic inhibition of adult-born neurons in the vDG promotes susceptibility to social defeat stress, whereas increasing neurogenesis confers resilience to chronic stress. By using in vivo calcium imaging to record neuronal activity from large cell populations in the vDG, we show that increased neurogenesis results in a decrease in the activity of stress-responsive cells that are active preferentially during attacks or while mice explore anxiogenic environments. These effects on dentate gyrus activity are necessary and sufficient for stress resilience, as direct silencing of the vDG confers resilience whereas excitation promotes susceptibility. Our results suggest that the activity of the vDG may be a key factor in determining individual levels of vulnerability to stress and related psychiatric disorders.},
author = {Anacker, Christoph and Luna, Victor M. and Stevens, Gregory S. and Millette, Amira and Shores, Ryan and Jimenez, Jessica C. and Chen, Briana and Hen, Ren{\'{e}}},
doi = {10.1038/s41586-018-0262-4},
file = {:Users/ozlem/Desktop/Anacker2018.pdf:pdf},
issn = {0028-0836},
journal = {Nature},
keywords = {Adult neurogenesis,Stress and resilience},
pages = {1},
pmid = {29950730},
publisher = {Springer US},
title = {{Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus}},
url = {http://www.nature.com/articles/s41586-018-0262-4},
year = {2018}
}
@article{Malhotra2015,
abstract = {BACKGROUND: In order to retrieve useful information from scientific literature and electronic medical records (EMR) we developed an ontology specific for Multiple Sclerosis (MS).$\backslash$n$\backslash$nMETHODS: The MS Ontology was created using scientific literature and expert review under the Prot{\'{e}}g{\'{e}} OWL environment. We developed a dictionary with semantic synonyms and translations to different languages for mining EMR. The MS Ontology was integrated with other ontologies and dictionaries (diseases/comorbidities, gene/protein, pathways, drug) into the text-mining tool SCAIView. We analyzed the EMRs from 624 patients with MS using the MS ontology dictionary in order to identify drug usage and comorbidities in MS. Testing competency questions and functional evaluation using F statistics further validated the usefulness of MS ontology.$\backslash$n$\backslash$nRESULTS: Validation of the lexicalized ontology by means of named entity recognition-based methods showed an adequate performance (F score = 0.73). The MS Ontology retrieved 80{\%} of the genes associated with MS from scientific abstracts and identified additional pathways targeted by approved disease-modifying drugs (e.g. apoptosis pathways associated with mitoxantrone, rituximab and fingolimod). The analysis of the EMR from patients with MS identified current usage of disease modifying drugs and symptomatic therapy as well as comorbidities, which are in agreement with recent reports.$\backslash$n$\backslash$nCONCLUSION: The MS Ontology provides a semantic framework that is able to automatically extract information from both scientific literature and EMR from patients with MS, revealing new pathogenesis insights as well as new clinical information.},
author = {Malhotra, Ashutosh and G{\"{u}}ndel, Michaela and Rajput, Abdul Mateen and Mevissen, Heinz Theodor and Saiz, Albert and Pastor, Xavier and Lozano-Rubi, Raimundo and Martinez-Lapsicina, Elena H. and Zubizarreta, Irati and Mueller, Bernd and Kotelnikova, Ekaterina and Toldo, Luca and Hofmann-Apitius, Martin and Villoslada, Pablo},
doi = {10.1371/journal.pone.0116718},
file = {:Users/ozlem/Desktop/papers/Disease Map Papers/pone.0116718.pdf:pdf},
isbn = {19326203 (Electronic)},
issn = {19326203},
journal = {PLoS ONE},
number = {2},
pages = {1--12},
pmid = {25665127},
title = {{Knowledge retrieval from pubmed abstracts and electronic medical records with the multiple sclerosis ontology}},
volume = {10},
year = {2015}
}
@article{Olayioye2000a,
abstract = {ErbB family:$\backslash$n$\backslash$nEGF receptor (= ErbB1/HER1)$\backslash$n$\backslash$nErbB2/Neu/HER2$\backslash$n$\backslash$nErbB3/HER3$\backslash$n$\backslash$nErbB4/HER4$\backslash$n$\backslash$n$\backslash$nligands: EGF-related peptide growth factors $\backslash$n$\backslash$n→ receptors form homo- and heterodimers$\backslash$n$\backslash$n$\backslash$n1. intrinsic tyrosine kinase activity of receptors stimulated$\backslash$n$\backslash$n2. autophosphorylation$\backslash$n$\backslash$n3. docking site for signaling molecules$\backslash$n$\backslash$n$\backslash$nErbB2: preferred dimerization partner for other ErbB receptors$\backslash$n$\backslash$n$\backslash$nErbB2 and ErbB3: stimulate mitogenic signaling networks$\backslash$n$\backslash$n→ uncontrolled tumor cell proliferation by a mechanism involving deregulation$\backslash$nof the G1-S transition$\backslash$n$\backslash$n$\backslash$nErbB1, ErbB2: increased proliferation?$\backslash$n$\backslash$n$\backslash$nTherapy:$\backslash$n$\backslash$na monoclonal antibody (4D5) targets extracellular domain of ErbB2:$\backslash$ninhibits in vitro growth of ErbB2 overexpressing tumor cells $\backslash$n$\backslash$nreduction of ErbB2 phorylation, inhibition of receptor signaling (unklar$\backslash$nwie Wirkung ist)$\backslash$n$\backslash$nhumanized version: Herceptin},
archivePrefix = {arXiv},
arxivId = {15334406},
author = {Olayioye, M A and Neve, R M and Lane, H A and Hynes, N E and Alimandi, M. and Romano, A. and Curia, MC. and Muraro, R. and Fedi, P. and Aaronson, SA. and Fiore, PP. Di and Kraus, MH. and Aroian, RV. and Koga, M. and Mendel, JE. and Ohshima, Y. and Sternberg, PW. and Barbacci, EG. and Guarino, BC. and Stroh, JG. and Singleton, DH. and Rosnack, KJ. and Moyer, JD. and Andrews, GC. and Bargmann, CI. and Hung, MC. and Weinberg, RA. and Baselga, J. and Batzer, AG. and Rotin, D. and Urena, JM. and Skolnik, EY. and Schlessinger, J. and Baulida, J. and Kraus, MH. and Alimandi, M. and Fiore, PP. Di and Carpenter, G. and Beerli, RR. and Hynes, NE. and Beerli, RR. and Wels, W. and Hynes, NE. and Beerli, RR. and Graus‐Porta, D. and Woods‐Cook, K. and Chen, X. and Yarden, Y. and Hynes, NE. and Biscardi, JS. and Maa, MC. and Tice, DA. and Cox, ME. and Leu, TH. and Parsons, SJ. and Biscardi, JS. and Tice, DA. and Parsons, SJ. and Bodey, B. and Bodey, B. and Groger, AM. and Luck, JV. and Siegel, SE. and Taylor, CR. and Kaiser, HE. and Britsch, S. and Li, L. and Kirchhoff, S. and Theuring, F. and Brinkmann, V. and Birchmeier, C. and Riethmacher, D. and Busfield, SJ. and Carpenter, G. and Carraway, KL. and Weber, JL. and Unger, MJ. and Ledesma, J. and Yu, N. and Gassmann, M. and Lai, K. and Chang, H. and Riese, DJ. and Gilbert, W. and Stern, DF. and McMahan, UJ. and Chattopadhyay, A. and Vecchi, M. and Ji, Q. and Mernaugh, R. and Carpenter, G. and Cobleigh, MA. and Cohen, BD. and Kiener, PA. and Green, JM. and Foy, L. and Fell, P. and Zhang, K. and Cohen, BD. and Green, JM. and Foy, L. and Fell, HP. and Dankort, DL. and Wang, Z. and Blackmore, V. and Moran, MF. and Muller, WJ. and Darcy, KM. and Zangani, D. and Wolhueter, AL. and Huang, RY. and Vaughan, MM. and Russell, JA. and Ip, MM. and DiGiovanna, MP. and Lerman, MA. and Coffey, RJ. and Muller, WJ. and Cardiff, RD. and Stern, DF. and Downward, J. and Parker, P. and Waterfield, MD. and Elenius, K. and Choi, CJ. and Paul, S. and Santiestevan, E. and Nishi, E. and Klagsbrun, M. and Erickson, SL. and O'Shea, KS. and Ghaboosi, N. and Loverro, L. and Frantz, G. and Bauer, M. and Lu, LH. and Moore, MW. and Fazioli, F. and Minichiello, L. and Matoskova, B. and Wong, WT. and Fiore, PP. Di and Fiddes, RJ. and Campbell, DH. and Janes, PW. and Sivertsen, SP. and Sasaki, H. and Wallasch, C. and Daly, RJ. and Fowler, KJ. and French, AR. and Tadaki, DK. and Niyogi, SK. and Lauffenburger, DA. and Gassmann, M. and Casagranda, F. and Orioli, D. and Simon, H. and Lai, C. and Klein, R. and Lemke, G. and Gilbertson, RJ. and Perry, RH. and Kelly, PJ. and Pearson, ADJ. and Lunee, J. and Graus‐Porta, D. and Beerli, RR. and Hynes, NE. and Graus‐Porta, D. and Beerli, RR. and Daly, JM. and Hynes, NE. and Groenen, LC. and Nice, EC. and Burgess, AW. and Guy, PM. and Platko, JV. and Cantley, LC. and Cerione, RA. and Carraway, KL. and Hackel, PO. and Zwick, E. and Prenzel, N. and Ullrich, A. and Harari, D. and Tzahar, E. and Romano, J. and Shelly, M. and Pierce, JH. and Andrews, GC. and Yarden, Y. and Hazan, R. and Margolis, B. and Dombalagian, M. and Ullrich, A. and Zilberstein, A. and Schlessinger, J. and Heldin, C‐H. and Hennighausen, L. and Robinson, GW. and Hsuan, JJ. and Totty, N. and Waterfield, MD. and Hudziak, RM. and Lewis, GD. and Winget, M. and Fendly, BM. and Shepard, HM. and Ullrich, A. and Hynes, NE. and Stern, DF. and Jannot, CB. and Beerli, RR. and Mason, S. and Gullick, WJ. and Hynes, NE. and Joazeiro, CAP. and Wing, SS. and Huang, HK. and Leverson, JD. and Hunter, T. and Liu, YC. and Jones, FE. and Stern, DF. and Jones, FE. and Welte, T. and Fu, XY. and Stern, DF. and Jones, JY. and Akita, RW. and Sliwkowski, MX. and Karunagaran, D. and Tzahar, E. and Beerli, RR. and Chen, X. and Graus‐Porta, D. and Ratzkin, BJ. and Seger, R. and Hynes, NE. and Yarden, Y. and Katsuura, M. and Tanaka, S. and Keilhack, H. and Tenev, T. and Nyakatura, E. and Godovac‐Zimmermann, J. and Nielsen, L. and Seedorf, K. and Bohmer, FD. and Kokai, Y. and Myers, JN. and Wada, T. and Brown, VI. and LeVea, CM. and Davis, JG. and Dobashi, K. and Greene, MI. and Kramer, R. and Bucay, B. and Kane, DJ. and Martin, LE. and Tarpley, JE. and Theill, LE. and Lane, HA. and Beuvink, I. and Motoyama, AB. and Daly, JM. and Neve, RM. and Hynes, NE. and Lee, KF. and Simon, H. and Chen, H. and Bates, B. and Hung, MC. and Hauser, C. and Lemmon, MA. and Bu, Z. and Ladbury, JE. and Zhou, M. and Pinchasi, D. and Lax, I. and Engelman, DM. and Schlessinger, J. and Lemoine, NR. and Barnes, DM. and Hollywood, DP. and Hughes, CM. and Smith, P. and Dublin, E. and Prigent, SA. and Gullick, WJ. and Hurst, HC. and Lesa, GM. and Sternberg, PW. and Levkowitz, G. and Klapper, LN. and Tzahar, E. and Freywald, A. and Sela, M. and Yarden, Y. and Levkowitz, G. and Lewis, GD. and Figari, I. and Fendly, B. and Wong, WL. and Carter, P. and Gorman, C. and Shepard, HM. and Lewis, GD. and Lofgren, JA. and McMurtrey, AE. and Huijens, A. and Fendly, BM. and Bauer, KD. and Sliwkowski, MX. and Luetteke, NC. and Qiu, TH. and Fenton, SE. and Troyer, KL. and Riedel, RF. and Chang, A. and Lee, DC. and Luttrell, LM. and Daaka, Y. and Lefkowitz, RJ. and Margolis, BL. and Lax, I. and Kris, R. and Dombalagian, M. and Honegger, AM. and Howk, R. and Givol, D. and Ullrich, A. and Schlessinger, J. and Massague, J. and Pandiella, A. and Meisner, H. and Daga, A. and Buxton, J. and Fernandez, B. and Chawla, A. and Banerjee, U. and Czech, MP. and Meyer, D. and Birchmeier, C. and Miettinen, PJ. and Berger, JE. and Meneses, J. and Phung, P. and Pedersen, RA. and Werb, Z. and Derynk, R. and Morris, JK. and Weichun, L. and Hauser, C. and Marchuk, Y. and Getman, D. and Lee, KF. and Neve, RM. and Sutterl{\"{u}}ty, H. and Pullen, N. and Lane, HA. and Daly, JM. and Krek, W. and Hynes, NE. and Ojeda, J. and Ma, YJ. and Okabayashi, Y. and Kido, Y. and Okutani, T. and Sugamoto, Y. and Sakaguchi, K. and Kasuga, M. and Okutani, T. and Okabayashi, Y. and Kido, Y. and Sugimoto, Y. and Sakaguchi, K. and Matuoka, K. and Takenawa, T. and Kasuga, M. and Olayioye, MA. and Graus‐Porta, D. and Beerli, RR. and Rohrer, J. and Gay, B. and Hynes, NE. and Olayioye, MA. and Beuvink, I. and Horsch, K. and Daly, JM. and Hynes, NE. and Paria, BC. and Elenius, K. and Klagsbrun, M. and Dey, SK. and Pegram, MD. and Peles, E. and Yarden, Y. and Pinkas‐Kramarski, R. and Prigent, SA. and Gullick, W. and Rajkumar, T. and Stamp, GWH. and Pandha, HS. and Waxman, J. and Gullick, WJ. and Ricci, A. and Lanfrancone, L. and Chiari, R. and Belardo, G. and Pertica, C. and Natali, PG. and Pelicci, PG. and Segatto, O. and Riese, DJ. and Stern, DF. and Riese, DJ. and van Raaij, TM. and Plowman, GD. and Andrews, GC. and Stern, DF. and Riese, DJ. and Bermingham, Y. and van Raaij, TM. and Buckley, S. and Plowman, GD. and Stern, DF. and Riethmacher, D. and Sonnenberg‐Riethmacher, E. and Brinkmann, V. and Yamaai, T. and Lewin, GR. and Birchneier, C. and Rotin, D. and Sakaguchi, K. and Okabayashi, Y. and Kido, Y. and Kimura, S. and Matsumura, Y. and Inushima, K. and Kasuga, M. and Salomon, DS. and Brandt, R. and Ciardiello, F. and Normanno, N. and Sato, K. and Sato, A. and Aoto, M. and Fukami, Y. and Schroeder, JA. and Lee, DC. and Segatto, O. and Lonardo, F. and Pierce, JH. and Bottaro, DP. and Fiore, PP. Di and Sherr, CJ. and Roberts, JM. and Shoelson, SE. and Sibilia, M. and Wagner, EF. and Sibilia, M. and Steinbach, JP. and Stingl, L. and Aguzzi, A. and Wagner, EF. and Siegel, PM. and Ryan, ED. and Cardiff, RD. and Muller, W. and Slamon, DJ. and Spencer, KSR. and Graus‐Porta, D. and Leng, J. and Hynes, NE. and Klemke, RL. and Stover, DR. and Becker, M. and Liebetanz, J. and Lydon, NB. and Sudol, M. and Tang, CK. and Lippman, ME. and Threadgill, DW. and Torrisi, MR. and Lotti, LV. and Belleudi, F. and Gradini, R. and Salcini, AE. and Confalonieri, S. and Pelicci, PG. and Fiore, PP. Di and Toyoda, H. and Komurasaki, T. and Uchida, D. and Morimoto, S. and Tzahar, E. and Waterman, H. and Chen, X. and Levkowitz, G. and Karunagaran, D. and Lavi, S. and Ratzkin, BJ. and Yarden, Y. and Tzahar, E. and Tzahar, E. and Wallasch, C. and Weiss, FU. and Niederfellner, G. and Jallal, B. and Issing, W. and Ullrich, A. and Walton, GM. and Chen, WS. and Rosenfeld, MG. and Gill, GN. and Wasserman, JD. and Freeman, M. and Waterman, H. and Sabanai, I. and Geiger, B. and Yarden, Y. and Weiner, DB. and Liu, J. and Cohen, JA. and Williams, WV. and Greene, MI. and Weiss, A. and Schlessinger, J. and Wiesen, JF. and Young, P. and Werb, Z. and Cunha, GR. and Xie, W. and Paterson, AJ. and Chin, E. and Nabell, LM. and Kudlow, JE. and Yang, Y. and Spitzer, E. and Meyer, D. and Sachs, M. and Niemann, C. and Hartmann, G. and Weidner, KM. and Birchmeier, C. and Birchmeier, W. and Yokouchi, M. and Kondo, T. and Houghton, A. and Bartkiewicz, M. and Horne, WC. and Zhang, H. and Yoshimura, A. and Baron, R. and Yoon, CH. and Lee, J. and Jongeward, GD. and Sternberg, PW. and Zhang, D. and Zhang, K. and Sun, J. and Liu, N. and Wen, D. and Chang, D. and Thomason, A. and Yoshinaga, SK. and Zrihan‐Licht, S. and Deng, B. and Yarden, Y. and McShan, G. and Keydar, I. and Avraham, H.},
doi = {10.1093/emboj/19.13.3159},
eprint = {15334406},
isbn = {0261-4189 (Print)$\backslash$n0261-4189 (Linking)},
issn = {0261-4189},
journal = {The EMBO journal},
pmid = {10880430},
title = {{The ErbB signaling network: receptor heterodimerization in development and cancer.}},
year = {2000}
}
@article{Dhillon2007,
author = {Dhillon, A S and Hagan, S and Rath, O and Kolch, W},
journal = {Oncogene},
month = {may},
pages = {3279},
publisher = {Nature Publishing Group},
title = {{MAP kinase signalling pathways in cancer}},
url = {https://doi.org/10.1038/sj.onc.1210421 http://10.0.4.14/sj.onc.1210421},
volume = {26},
year = {2007}
}
@misc{Butcher2004,
abstract = {The hope of the rapid translation of 'genes to drugs' has foundered on the reality that disease biology is complex, and that drug development must be driven by insights into biological responses. Systems biology aims to describe and to understand the operation of complex biological systems and ultimately to develop predictive models of human disease. Although meaningful molecular level models of human cell and tissue function are a distant goal, systems biology efforts are already influencing drug discovery. Large-scale gene, protein and metabolite measurements ('omics') dramatically accelerate hypothesis generation and testing in disease models. Computer simulations integrating knowledge of organ and system-level responses help prioritize targets and design clinical trials. Automation of complex primary human cell-based assay systems designed to capture emergent properties can now integrate a broad range of disease-relevant human biology into the drug discovery process, informing target and compound validation, lead optimization, and clinical indication selection. These systems biology approaches promise to improve decision making in pharmaceutical development.},
author = {Butcher, Eugene C. and Berg, Ellen L. and Kunkel, Eric J.},
booktitle = {Nature Biotechnology},
doi = {10.1038/nbt1017},
isbn = {1087-0156 (Print) 1087-0156 (Linking)},
issn = {10870156},
pmid = {15470465},
title = {{Systems biology in drug discovery}},
year = {2004}
}
@article{Ran2013,
abstract = {Targeted genome editing technologies have enabled a broad range of research and medical applications. The Cas9 nuclease from the microbial CRISPR-Cas system is targeted to specific genomic loci by a 20 nt guide sequence, which can tolerate certain mismatches to the DNA target and thereby promote undesired off-target mutagenesis. Here, we describe an approach that combines a Cas9 nickase mutant with paired guide RNAs to introduce targeted double-strand breaks. Because individual nicks in the genome are repaired with high fidelity, simultaneous nicking via appropriately offset guide RNAs is required for double-stranded breaks and extends the number of specifically recognized bases for target cleavage. We demonstrate that using paired nicking can reduce off-target activity by 50- to 1,500-fold in cell lines and to facilitate gene knockout in mouse zygotes without sacrificing on-target cleavage efficiency. This versatile strategy enables a wide variety of genome editing applications that require high specificity. {\textcopyright} 2013 Elsevier Inc.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Ran, F. Ann and Hsu, Patrick D. and Lin, Chie Yu and Gootenberg, Jonathan S. and Konermann, Silvana and Trevino, Alexandro E. and Scott, David A. and Inoue, Azusa and Matoba, Shogo and Zhang, Yi and Zhang, Feng},
doi = {10.1016/j.cell.2013.08.021},
eprint = {NIHMS150003},
isbn = {1097-4172 (Electronic)$\backslash$r0092-8674 (Linking)},
issn = {00928674},
journal = {Cell},
number = {6},
pages = {1380--1389},
pmid = {23992846},
title = {{Double nicking by RNA-guided CRISPR cas9 for enhanced genome editing specificity}},
volume = {154},
year = {2013}
}
@misc{Kraszewska2008,
abstract = {Nudix hydrolases are a family of proteins defined by a conserved amino-acid sequence GX(5)-EX(7)REUXEEXGU, where U is a hydrophobic residue. These enzymes are widely distributed among all classes of organisms and catalyze, with varying degrees of substrate specificity, the hydrolysis of a variety of nucleoside diphosphate derivatives: nucleoside di- and triphosphates and their oxidized forms, dinucleoside polyphosphates, nucleotide sugars, NADH, coenzyme A and the mRNA cap. Nudix proteins are postulated to control the cellular concentration of these compounds. The genome of the model plant Arabidopsis thaliana contains 29 genes coding for putative Nudix hydrolases. Recently, several Arabidopsis Nudix genes have been cloned and their products characterized. This review summarizes current knowledge on these plant enzymes and discusses their possible cellular functions.},
author = {Kraszewska, Elzbieta},
booktitle = {Acta Biochimica Polonica},
isbn = {0001-527X},
issn = {0001527X},
keywords = {Arabidopsis thaliana,MutT,Nudix,hydrolase,plant,pyrophosphohydrolase},
number = {4},
pages = {663--671},
pmid = {19081844},
title = {{The plant Nudix hydrolase family}},
volume = {55},
year = {2008}
}
@article{Kauffman1969,
abstract = {Proto-organisms probably were randomly aggregated nets of chemical reactions. The hypothesis that contemporary organisms are also randomly constructed molecular automata is examined by modeling the gene as a binary (on-off) device and studying the behavior of large, randomly constructed nets of these binary "genes". The results suggest that, if each "gene" is directly affected by two or three other "genes", then such random nets: behave with great order and stability; undergo behavior cycles whose length predicts cell replication time as a function of the number of genes per cell; possess different modes of behavior whose number per net predicts roughly the number of cell types in an organism as a function of its number of genes; and under the stimulus of noise are capable of differentiating directly from any mode of behavior to at most a few other modes of behavior. Cellular differentation is modeled as a Markov chain among the modes of behavior of a genetic net. The possibility of a general theory of metabolic behavior is suggested. {\textcopyright} 1969.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Kauffman, S. A.},
doi = {10.1016/0022-5193(69)90015-0},
eprint = {NIHMS150003},
isbn = {0022-5193 (Print)},
issn = {10958541},
journal = {Journal of Theoretical Biology},
pmid = {5803332},
title = {{Metabolic stability and epigenesis in randomly constructed genetic nets}},
year = {1969}
}
@article{Domitrovic2006,
abstract = {Msn2 and Msn4 transcription factors activate expression of stress-responsive element (STRE) controlled genes in response to various stresses triggering the environmental stress response in Saccharomyces cerevisiae. Although high hydrostatic pressure is known to induce gene expression modification in yeast, the transcription factors involved in this response are currently uncharacterized. In this work, we show that elevated pressure activates STRE dependent transcription through Msn2/4, which are also required for cell resistance and cell adaptation to high pressure. Moreover, it was demonstrated that HSP12 induction after a 50 MPa treatment is largely dependent on Msn2/4, while other transcription factors are involved in HSP12 over-expression after a 100 MPa treatment. {\textcopyright} 2006 Federation of European Biochemical Societies.},
author = {Domitrovic, Tatiana and Fernandes, Caroline Mota and Boy-Marcotte, Emmanuelle and Kurtenbach, Eleonora},
doi = {10.1016/j.febslet.2006.10.007},
isbn = {0014-5793 (Print) 0014-5793 (Linking)},
issn = {00145793},
journal = {FEBS Letters},
keywords = {Hydrostatic pressure,Msn2,Msn4,Stress,cAMP},
number = {26},
pages = {6033--6038},
pmid = {17055490},
title = {{High hydrostatic pressure activates gene expression through Msn2/4 stress transcription factors which are involved in the acquired tolerance by mild pressure precondition in Saccharomyces cerevisiae}},
volume = {580},
year = {2006}
}
@article{Margolin2006b,
abstract = {We describe a computational protocol for the ARACNE algorithm, an information-theoretic method for identifying transcriptional interactions between gene products using microarray expression profile data. Similar to other algorithms, ARACNE predicts potential functional associations among genes, or novel functions for uncharacterized genes, by identifying statistical dependencies between gene products. However, based on biochemical validation, literature searches and DNA binding site enrichment analysis, ARACNE has also proven effective in identifying bona fide transcriptional targets, even in complex mammalian networks. Thus we envision that predictions made by ARACNE, especially when supplemented with prior knowledge or additional data sources, can provide appropriate hypotheses for the further investigation of cellular networks. While the examples in this protocol use only gene expression profile data, the algorithm's theoretical basis readily extends to a variety of other high-throughput measurements, such as pathway-specific or genome-wide proteomics, microRNA and metabolomics data. As these data become readily available, we expect that ARACNE might prove increasingly useful in elucidating the underlying interaction models. For a microarray data set containing approximately 10,000 probes, reconstructing the network around a single probe completes in several minutes using a desktop computer with a Pentium 4 processor. Reconstructing a genome-wide network generally requires a computational cluster, especially if the recommended bootstrapping procedure is used.},
author = {Margolin, Adam A. and Wang, Kai and Lim, Wei Keat and Kustagi, Manjunath and Nemenman, Ilya and Califano, Andrea},
doi = {10.1038/nprot.2006.106},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Margolin et al. - 2006 - Reverse engineering cellular networks(2).pdf:pdf},
isbn = {1750-2799 (Electronic)},
issn = {17542189},
journal = {Nature Protocols},
number = {2},
pages = {662--671},
pmid = {17406294},
title = {{Reverse engineering cellular networks}},
volume = {1},
year = {2006}
}
@inproceedings{Berven2000,
abstract = {The 70 kDa ribosomal S6 kinase (p70S6K) is activated by numerous mitogens, growth factors and hormones. Activation of p70S6K occurs through phosphorylation at a number of sites and the primary target of the activated kinase is the 40S ribosomal protein S6, a major component of the machinery involved in protein synthesis in mammalian cells. In addition to its involvement in regulating translation, p70S6K activation has been implicated in cell cycle control and neuronal cell differentiation. Recent data obtained in this laboratory suggests that p70S6K may also function in regulating cell motility, a cellular response that is important in tumour metastases, the immune response and tissue repair. The present paper reviews the regulation and cellular function of p70S6K and proposes a novel function of p70S6K in regulating cell motility.},
author = {Berven, L. A. and Crouch, M. F.},
booktitle = {Immunology and Cell Biology},
doi = {10.1046/j.1440-1711.2000.00928.x},
issn = {08189641},
pmid = {10947872},
title = {{Cellular function of p70(S6K): A role in regulating cell motility}},
year = {2000}
}
@article{Calzone2010,
abstract = {Cytokines such as TNF and FASL can trigger death or survival depending on cell lines and cellular conditions. The mechanistic details of how a cell chooses among these cell fates are still unclear. The understanding of these processes is important since they are altered in many diseases, including cancer and AIDS. Using a discrete modelling formalism, we present a mathematical model of cell fate decision recapitulating and integrating the most consistent facts extracted from the literature. This model provides a generic high-level view of the interplays between NFkappaB pro-survival pathway, RIP1-dependent necrosis, and the apoptosis pathway in response to death receptor-mediated signals. Wild type simulations demonstrate robust segregation of cellular responses to receptor engagement. Model simulations recapitulate documented phenotypes of protein knockdowns and enable the prediction of the effects of novel knockdowns. In silico experiments simulate the outcomes following ligand removal at different stages, and suggest experimental approaches to further validate and specialise the model for particular cell types. We also propose a reduced conceptual model implementing the logic of the decision process. This analysis gives specific predictions regarding cross-talks between the three pathways, as well as the transient role of RIP1 protein in necrosis, and confirms the phenotypes of novel perturbations. Our wild type and mutant simulations provide novel insights to restore apoptosis in defective cells. The model analysis expands our understanding of how cell fate decision is made. Moreover, our current model can be used to assess contradictory or controversial data from the literature. Ultimately, it constitutes a valuable reasoning tool to delineate novel experiments.},
author = {Calzone, Laurence and Tournier, Laurent and Fourquet, Simon and Thieffry, Denis and Zhivotovsky, Boris and Barillot, Emmanuel and Zinovyev, Andrei},
doi = {10.1371/journal.pcbi.1000702},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/pcbi{\_}1000702{\_}pdf.pdf:pdf},
isbn = {1553-7358 (Electronic)$\backslash$n1553-734X (Linking)},
issn = {1553734X},
journal = {PLoS Computational Biology},
pmid = {20221256},
title = {{Mathematical modelling of cell-fate decision in response to death receptor engagement}},
year = {2010}
}
@misc{Andrews2010,
abstract = {FastQC aims to provide a simple way to do some quality control checks on raw sequence data coming from high throughput sequencing pipelines. It provides a modular set of analyses which you can use to give a quick impression of whether your data has any problems of which you should be aware before doing any further analysis. The main functions of FastQC are Import of data from BAM, SAM or FastQ files (any variant) Providing a quick overview to tell you in which areas there may be problems Summary graphs and tables to quickly assess your data Export of results to an HTML based permanent report Offline operation to allow automated generation of reports without running the interactive application},
author = {Andrews, Simon},
booktitle = {Http://Www.Bioinformatics.Babraham.Ac.Uk/Projects/Fastqc/},
doi = {citeulike-article-id:11583827},
pages = {http://www.bioinformatics.babraham.ac.uk/projects/},
title = {{FastQC: A quality control tool for high throughput sequence data.}},
year = {2010}
}
@article{Ha2018,
abstract = {Personalized (patient-specific) approaches have recently emerged with a precision medicine paradigm that acknowledges the fact that molecular pathway structures and activity might be considerably different within and across tumors. The functional cancer genome and proteome provide rich sources of information to identify patient-specific variations in signaling pathways and activities within and across tumors; however, current analytic methods lack the ability to exploit the diverse and multi-layered architecture of these complex biological networks. We assessed pan-cancer pathway activities for {\textgreater}7700 patients across 32 tumor types from The Cancer Proteome Atlas by developing a personalized cancer-specific integrated network estimation (PRECISE) model. PRECISE is a general Bayesian framework for integrating existing interaction databases, data-driven de novo causal structures, and upstream molecular profiling data to estimate cancer-specific integrated networks, infer patient-specific networks and elicit interpretable pathway-level signatures. PRECISE-based pathway signatures, can delineate pan-cancer commonalities and differences in proteomic network biology within and across tumors, demonstrates robust tumor stratification that is both biologically and clinically informative and superior prognostic power compared to existing approaches. Towards establishing the translational relevance of the functional proteome in research and clinical settings, we provide an online, publicly available, comprehensive database and visualization repository of our findings (
                  https://mjha.shinyapps.io/PRECISE/
                  
                ).},
author = {Ha, Min Jin and Banerjee, Sayantan and Akbani, Rehan and Liang, Han and Mills, Gordon B. and Do, Kim-Anh and Baladandayuthapani, Veerabhadran},
doi = {10.1038/s41598-018-32682-x},
file = {:Users/ozlem/Dropbox/papers/Biological Networks/s41598-018-32682-x.pdf:pdf},
issn = {2045-2322},
journal = {Scientific Reports},
number = {1},
pages = {14924},
publisher = {Springer US},
title = {{Personalized Integrated Network Modeling of the Cancer Proteome Atlas}},
url = {http://www.nature.com/articles/s41598-018-32682-x},
volume = {8},
year = {2018}
}
@article{Yung2008,
abstract = {We have analysed the influence of neighbouring base sequences on the mutagenesis induced by 7,8-dihydro-8-oxoguanine (8-oxoG or G(o)), a typical oxidative lesion of DNA, using the yeast oligonucleotide transformation technique. Two oligonucleotides, oligo-CCG(o) and oligo-CGG(o), each possessing a single 8-oxoG residue and represented by the sequences 5'-CCG(o)-3' and 5'-CGG(o)-3', respectively, were introduced into a chromosome of Saccharomyces cerevisiae and their mutagenic potentials were compared. In a wild-type strain, 8-oxoG showed very weak mutagenic potential in both cases. However, the lesion in 5'-CCG(o)-3' can cause efficient G-to-T transversion in a strain lacking the rad30 gene which encodes yeast DNA polymerase eta (Ypoleta). To explore the properties associated with this translesion synthesis (TLS), the same two oligonucleotides possessing an 8-oxoG were used as templates for a standing-start primer extension assay, and the nucleotide incorporation opposite 8-oxoG was investigated. We found that dATP incorporation opposite 8-oxoG with Ypoleta was low for both sequences. In particular, very low dATP incorporation was observed for the 5'-CCG(o)-3' sequence. These results account for the efficient inhibition of mutagenesis by Ypoleta. TLS plays an important role in one DNA sequence in terms of avoiding mutagenesis induced by 8-oxoG in yeast. In contrast, human yeast DNA polymerase eta showed higher dATP incorporation rates even with the 5'-CCG(o)-3' sequence.},
author = {Yung, Chin Wei and Okugawa, Yoji and Otsuka, Chie and Okamoto, Keinosuke and Arimoto, Sakae and Loakes, David and Negishi, Kazuo and Negishi, Tomoe},
doi = {10.1093/mutage/gen044},
issn = {02678357},
journal = {Mutagenesis},
number = {6},
pages = {509--513},
pmid = {18765421},
title = {{Influence of neighbouring base sequences on the mutagenesis induced by 7,8-dihydro-8-oxoguanine in yeast}},
volume = {23},
year = {2008}
}
@article{Xiao2012,
abstract = {Carbon nanotube (CNT) modification of microelectrodes can result in increased sensitivity without compromising time response. However, dip coating CNTs is not very reproducible and the CNTs tend to lay flat on the electrode surface which limits access to the electroactive sites on the ends. In this study, aligned CNT forests were formed using a chemical self-assembly method, which resulted in more exposed CNT ends to the analyte. Shortened, carboxylic acid functionalized single-walled CNTs were assembled from a dimethylformamide (DMF) suspension onto a carbon-fiber disk microelectrode modified with a thin iron hydroxide-decorated Nafion film. The modified electrodes were highly sensitive, with 36-fold higher oxidation currents for dopamine using fast-scan cyclic voltammetry than bare electrodes and 34-fold more current than electrodes dipped in CNTs. The limit of detection (LOD) for dopamine was 17 ± 3 nMat a 10 Hz repetition rate and 65 ± 7 nM at 90 Hz. The LOD at 90 Hz was the same as a bare electrode at 10 Hz, allowing a 9-fold increase in temporal resolution without a decrease in sensitivity. Similar increases were observed for other cationic catecholamine neurotransmitters, and the increases in current were greater than for anionic interferents such as ascorbic acid and 3,4-dihydroxyphenylacetic acid (DOPAC). The CNT forest electrodes had high sensitivity at 90 Hz repetition rate when stimulated dopamine release was measured in Drosophila. The sensitivity, temporal resolution, and spatial resolution of these CNT forest modified disk electrodes facilitate enhanced electrochemical measurements of neurotransmitter release in vivo},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Xiao, Ning and Venton, B. Jill},
doi = {10.1021/ac301445w},
eprint = {NIHMS150003},
isbn = {0003-2700},
issn = {00032700},
journal = {Analytical Chemistry},
number = {18},
pages = {7816--7822},
pmid = {22823497},
title = {{Rapid, sensitive detection of neurotransmitters at microelectrodes modified with self-assembled SWCNT forests}},
volume = {84},
year = {2012}
}
@article{Faure2006,
abstract = {MOTIVATION: To understand the behaviour of complex biological regulatory networks, a proper integration of molecular data into a full-fledge formal dynamical model is ultimately required. As most available data on regulatory interactions are qualitative, logical modelling offers an interesting framework to delineate the main dynamical properties of the underlying networks. RESULTS: Transposing a generic model of the core network controlling the mammalian cell cycle into the logical framework, we compare different strategies to explore its dynamical properties. In particular, we assess the respective advantages and limits of synchronous versus asynchronous updating assumptions to delineate the asymptotical behaviour of regulatory networks. Furthermore, we propose several intermediate strategies to optimize the computation of asymptotical properties depending on available knowledge. AVAILABILITY: The mammalian cell cycle model is available in a dedicated XML format (GINML) on our website, along with our logical simulation software GINsim (http://gin.univ-mrs.fr/GINsim). Higher resolution state transitions graphs are also found on this web site (Model Repository page).},
author = {Faur{\'{e}}, Adrien and Naldi, Aur{\'{e}}lien and Chaouiya, Claudine and Thieffry, Denis},
doi = {10.1093/bioinformatics/btl210},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Faur{\'{e}} et al. - 2006 - Dynamical analysis of a generic Boolean model for the control of the mammalian cell cycle.pdf:pdf},
isbn = {1460-2059 (Electronic)},
issn = {13674803},
journal = {Bioinformatics},
number = {14},
pages = {124--131},
pmid = {16873462},
title = {{Dynamical analysis of a generic Boolean model for the control of the mammalian cell cycle}},
volume = {22},
year = {2006}
}
@article{Zetsche2015,
abstract = {Summary The microbial adaptive immune system CRISPR mediates defense against foreign genetic elements through two classes of RNA-guided nuclease effectors. Class 1 effectors utilize multi-protein complexes, whereas class 2 effectors rely on single-component effector proteins such as the well-characterized Cas9. Here, we report characterization of Cpf1, a putative class 2 CRISPR effector. We demonstrate that Cpf1 mediates robust DNA interference with features distinct from Cas9. Cpf1 is a single RNA-guided endonuclease lacking tracrRNA, and it utilizes a T-rich protospacer-adjacent motif. Moreover, Cpf1 cleaves DNA via a staggered DNA double-stranded break. Out of 16 Cpf1-family proteins, we identified two candidate enzymes from Acidaminococcus and Lachnospiraceae, with efficient genome-editing activity in human cells. Identifying this mechanism of interference broadens our understanding of CRISPR-Cas systems and advances their genome editing applications.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Zetsche, Bernd and Gootenberg, Jonathan S. and Abudayyeh, Omar O. and Slaymaker, Ian M. and Makarova, Kira S. and Essletzbichler, Patrick and Volz, Sara E. and Joung, Julia and {Van Der Oost}, John and Regev, Aviv and Koonin, Eugene V. and Zhang, Feng},
doi = {10.1016/j.cell.2015.09.038},
eprint = {NIHMS150003},
isbn = {6176321972},
issn = {10974172},
journal = {Cell},
number = {3},
pages = {759--771},
pmid = {26422227},
title = {{Cpf1 Is a Single RNA-Guided Endonuclease of a Class 2 CRISPR-Cas System}},
volume = {163},
year = {2015}
}
@misc{Cox2003,
abstract = {Mutational activation of Ras promotes oncogenesis by disrupting a multitude of normal cellular processes. Perhaps, best characterized and understood are the mechanisms by which oncogenic Ras promotes deregulated cell cycle progression and uncontrolled cellular proliferation. However, it is now clear that oncogenic Ras can also deregulate processes that control apoptosis. In light of the diversity of downstream effector targets known to facilitate Ras function, it is perhaps not surprising that Ras regulation of cell survival is complex, involving the balance and interplay of multiple signaling networks. While our understanding of these events is still far from complete, and is complicated by cell type and signaling context differences, several important mechanisms have begun to emerge. We review the role and mechanism of specific effectors in regulating the antiapoptotic (Raf, phosphatidylinositol 3-kinase and Tiam1) and apoptotic (Nore1 and RASSF1) actions of oncogenic Ras, and discuss the possibility that the effector actions of p120RasGAP make a significant contribution to Ras regulation of apoptotic events.},
author = {Cox, Adrienne D. and Der, Channing J.},
booktitle = {Oncogene},
doi = {10.1038/sj.onc.1207111},
isbn = {0950-9232},
issn = {09509232},
keywords = {Apoptosis,Ras,Signal transduction,Small GTPase},
pmid = {14663478},
title = {{The dark side of Ras: Regulation of apoptosis}},
year = {2003}
}
@article{Montagud2017,
abstract = {Mathematical models can serve as a tool to formalize biological knowledge from diverse sources, to investigate biological questions in a formal way, to test experimental hypotheses, to predict the effect of perturbations and to identify underlying mechanisms. We present a pipeline of computational tools that performs a series of analyses to explore a logical model's properties. A logical model of initiation of the metastatic process in cancer is used as a transversal example. We start by analysing the structure of the interaction network constructed from the literature or existing databases. Next, we show how to translate this network into a mathematical object, specifically a logical model, and how robustness analyses can be applied to it. We explore the visualization of the stable states, defined as specific attractors of the model, and match them to cellular fates or biological read-outs. With the different tools we present here, we explain how to assign to each solution of the model a probability and how to identify genetic interactions using mutant phenotype probabilities. Finally, we connect the model to relevant experimental data: we present how some data analyses can direct the construction of the network, and how the solutions of a mathematical model can also be compared with experimental data, with a particular focus on high-throughput data in cancer biology. A step-by-step tutorial is provided as a Supplementary Material and all models, tools and scripts are provided on an accompanying website: https://github.com/sysbio-curie/Logical{\_}modelling{\_}pipeline.},
author = {Montagud, Arnau and Traynard, Pauline and Martignetti, Loredana and Bonnet, Eric and Barillot, Emmanuel and Zinovyev, Andrei and Calzone, Laurence},
doi = {10.1093/bib/bbx163},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Montagud et al. - 2017 - Conceptual and computational framework for logical modelling of biological networks deregulated in diseases.pdf:pdf},
issn = {1467-5463},
journal = {Briefings in Bioinformatics},
keywords = {data integration,genetic interaction,logical modelling,pipeline of tools,robustness analysis,step-by-step},
number = {October 2017},
pages = {1--12},
title = {{Conceptual and computational framework for logical modelling of biological networks deregulated in diseases}},
url = {http://academic.oup.com/bib/advance-article/doi/10.1093/bib/bbx163/4716963},
year = {2017}
}
@article{Miele1996,
abstract = {A quantitative method consisting of the modification of the zero net flux technique was used to determine the extracellular concentration of ascorbate. A carbon paste electrode (CPE) held at constant potential was combined with a microdialysis probe through which various concentrations of ascorbate were locally infused. In experiments with bilateral CPEs, one of which was combined with a dialysis probe, no difference was observed in either basal or stimulated ascorbate currents. Addition of different concentrations of ascorbate to the perfusion fluid produced rapid changes in the voltammetric current due to ascorbate oxidation. Irrespective of the concentration of ascorbate infused, the current returned to basal level when the perfusion was stopped. The return was found to be more rapid after infusion of concentrations of ascorbate higher than the extracellular concentration than after perfusion with ascorbate-free solutions. This demonstrates that homeostasis of ascorbate occurs in vivo. The calculated point of zero net flux was 416 ?? 66 ??M (n = 6). This represents the extracellular concentration of ascorbate.},
author = {Miele, M. and Fillenz, M.},
doi = {10.1016/S0165-0270(96)00094-5},
isbn = {0165-0270 (Print)},
issn = {01650270},
journal = {Journal of Neuroscience Methods},
keywords = {ascorbate,extracellular concentration, in vivo,homeostasis,rat striatum,unanaesthetised rat,voltammetry},
number = {1},
pages = {15--19},
pmid = {8982976},
title = {{In vivo determination of extracellular brain ascorbate}},
volume = {70},
year = {1996}
}
@misc{Siksnys2016,
abstract = {Papers by Anders et al. (2016) and Hirano et al. (2016b), published in this issue of Molecular Cell, show that SpCas9 uses an induced fit mechanism to recognize altered protospacer adjacent motif (PAM) sequences. Papers by Anders et al. and Hirano et al., published in this issue of Molecular Cell, show that SpCas9 uses an induced fit mechanism to recognize altered protospacer adjacent motif (PAM) sequences.},
author = {Siksnys, Virginijus and Gasiunas, Giedrius},
booktitle = {Molecular Cell},
doi = {10.1016/j.molcel.2016.03.002},
issn = {10974164},
number = {6},
pages = {793--794},
pmid = {26990984},
title = {{Rewiring Cas9 to Target New PAM Sequences}},
volume = {61},
year = {2016}
}
@article{Soltoff1994,
abstract = {Conflicting results concerning the ability of the epidermal growth factor (EGF) receptor to associate with and/or activate phosphatidylinositol (PtdIns) 3-kinase have been published. Despite the ability of EGF to stimulate the production of PtdIns 3-kinase products and to cause the appearance of PtdIns 3-kinase activity in antiphosphotyrosine immunoprecipitates in several cell lines, we did not detect EGF-stimulated PtdIns 3-kinase activity in anti-EGF receptor immunoprecipitates. This result is consistent with the lack of a phosphorylated Tyr-X-X-Met motif, the p85 Src homology 2 (SH2) domain recognition sequence, in this receptor sequence. The EGF receptor homolog, ErbB2 protein, also lacks this motif. However, the ErbB3 protein has seven repeats of the Tyr-X-X-Met motif in the carboxy-terminal unique domain. Here we show that in A431 cells, which express both the EGF receptor and ErbB3, PtdIns 3-kinase coprecipitates with the ErbB3 protein (p180erbB3) in response to EGF. p180erbB3 is also shown to be tyrosine phosphorylated in response to EGF. In contrast, a different mechanism for the activation of PtdIns 3-kinase in response to EGF occurs in certain cells (PC12 and A549 cells). Thus, we show for the first time that ErbB3 can mediate EGF responses in cells expressing both ErbB3 and the EGF receptor.},
author = {Soltoff, SP and Carraway, KL},
doi = {10.1128/MCB.14.6.3550.Updated},
isbn = {0270-7306 (Print)$\backslash$r0270-7306 (Linking)},
issn = {0270-7306},
journal = {{\ldots} and cellular biology},
pmid = {7515147},
title = {{ErbB3 is involved in activation of phosphatidylinositol 3-kinase by epidermal growth factor.}},
year = {1994}
}
@misc{Lee2009,
abstract = {Epidermal growth factor receptor (EGFR) is a representative model of receptor tyrosine kinases (RTKs), and offers a means of understanding their common principles and fundamental mechanisms. Furthermore, EGFR plays an essential role in cell proliferation and migration, and the disruption of EGFR signaling has been implicated in the development and growth of cancer. Phospholipase D (PLD) is a key mediator of EGFR function, and can be directly regulated by upstream binding partners in an EGF-dependent manner. PLD regulates downstream molecules by generating phosphatidic acid (PA), but it also dynamically interacts with a variety of intracellular molecules and these interactions spatiotemporally regulate EGFR function and serve as a hub that orchestrates signaling flow. This review summarizes the interrelationship between PLD and its binding molecules in the context of EGFR signaling, and addresses the roles of PLD in the mediation and coordination of this signaling. {\textcopyright} 2009 Elsevier B.V. All rights reserved.},
author = {Lee, Chang Sup and Kim, Kyung Lock and Jang, Jin Hyeok and Choi, Yoon Sup and Suh, Pann Ghill and Ryu, Sung Ho},
booktitle = {Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids},
doi = {10.1016/j.bbalip.2009.04.007},
isbn = {0006-3002 (Print)$\backslash$r0006-3002 (Linking)},
issn = {13881981},
keywords = {Coordination,Epidermal growth factor receptor (EGFR),Interaction,Phospholipase D (PLD),Phox homology (PX) domain},
pmid = {19410013},
title = {{The roles of phospholipase D in EGFR signaling}},
year = {2009}
}
@article{Chuang2010,
abstract = {Systems biology provides a framework for assembling models of biological systems from systematic measurements. Since the field was first introduced a decade ago, considerable progress has been made in technologies for global cell measurement and in computational analyses of these data to map and model cell function. It has also greatly expanded into the translational sciences, with approaches pioneered in yeast now being applied to elucidate human development and disease. Here, we review the state of the field with a focus on four emerging applications of systems biology that are likely to be of particular importance during the decade to follow: (a) pathway-based biomarkers, (b) global genetic interaction maps, (c) systems approaches to identify disease genes, and (d) stem cell systems biology. We also cover recent advances in software tools that allow biologists to explore system-wide models and to formulate new hypotheses. The applications and methods covered in this review provide a set of prime exemplars useful to cell and developmental biologists wishing to apply systems approaches to areas of interest.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Chuang, Han-Yu and Hofree, Matan and Ideker, Trey},
doi = {10.1146/annurev-cellbio-100109-104122},
eprint = {NIHMS150003},
isbn = {10.1146/annurev-cellbio-100109-104122},
issn = {1081-0706},
journal = {Annual Review of Cell and Developmental Biology},
pmid = {20604711},
title = {{A Decade of Systems Biology}},
year = {2010}
}
@article{Testa2007,
abstract = {This review continues a general presentation of the metabolism of drugs and other xenobiotics started in a recent issue of Chemistry {\&} Biodiversity. This Part 2 presents the numerous oxidoreductases involved, their nomenclature, relevant biochemical properties, catalytic mechanisms, and the very diverse reactions they catalyze. Many medicinally, environmentally, and toxicologically relevant examples are presented and discussed. Cytochromes P450 occupy a majority of the pages of Part 2, but a large number of relevant oxidoreductases are also considered, e.g., flavin-containing monooxygenases, amine oxidases, molybdenum hydroxylases, peroxidases, and the innumerable dehydrogenases/reductases.},
author = {Testa, B and Kramer, S D},
doi = {10.1002/cbdv.200790032},
isbn = {1612-1880 (Electronic)$\backslash$r1612-1872 (Linking)},
issn = {1612-1880},
journal = {Chem Biodivers},
keywords = {*Oxidation-Reduction,Animals,Cytochrome P-450 Enzyme System/*chemistry/*metabol,Humans,Oxidoreductases/*chemistry/metabolism,Xenobiotics/*chemistry/*metabolism},
number = {3},
pages = {257--405},
pmid = {17372942},
title = {{The biochemistry of drug metabolism--an introduction: Part 2. Redox reactions and their enzymes}},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve{\&}db=PubMed{\&}dopt=Citation{\&}list{\_}uids=17372942},
volume = {4},
year = {2007}
}
@book{Ilari2008,
abstract = {X-ray biocrystallography is the most powerful method to obtain a macromolecular structure. The improvement of computational technologies in recent years and the development of new and powerful computer programs together with the enormous increment in the number of protein structures deposited in the Protein Data Bank, render the resolution of new structures easier than in the past. The aim of this chapter is to provide practical procedures useful for solving a new structure. It is impossible to give more than a flavor of what the x-ray crystallographic technique entails in one brief chapter; therefore, this chapter focuses its attention on the Molecular Replacement method. Whenever applicable, this method allows the resolution of macromolecular structures starting from a single data set and a search model downloaded from the PDB, with the aid only of computer work.},
author = {Ilari, Andrea and Savino, Carmelinda},
booktitle = {Methods in molecular biology (Clifton, N.J.)},
doi = {10.1007/978-1-60327-159-2_3},
isbn = {9781461439561},
issn = {1064-3745},
keywords = {Crystallography, X-Ray,Crystallography, X-Ray: methods,Databases, Protein,Protein Conformation,Proteins,Proteins: chemistry},
pages = {63--87},
pmid = {18563369},
title = {{Protein structure determination by x-ray crystallography.}},
url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3625376{\&}tool=pmcentrez{\&}rendertype=abstract},
volume = {452},
year = {2008}
}
@misc{Silva2012,
abstract = {The incidence of infections caused by Candida species (candidosis) has increased considerably over the past three decades, mainly due to the rise of the AIDS epidemic, an increasingly aged population, higher numbers of immunocompromised patients and the more widespread use of indwelling medical devices. Candida albicans is the main cause of candidosis; however, non-C. albicans Candida (NCAC) species such as Candida glabrata, Candida tropicalis and Candida parapsilosis are now frequently identified as human pathogens. The apparent increased emergence of these species as human pathogens can be attributed to improved identification methods and also associated with the degree of diseases of the patients, the interventions that they were subjected and the drugs used. Candida pathogenicity is facilitated by a number of virulence factors, most importantly adherence to host surfaces including medical devices, biofilm formation and secretion of hydrolytic enzymes (e.g. proteases, phospholipases and haemolysins). Furthermore, despite extensive research to identify pathogenic factors in fungi, particularly in C. albicans, relatively little is known about NCAC species. This review provides information on the current state of knowledge on the biology, identification, epidemiology, pathogenicity and antifungal resistance of C. glabrata, C. parapsilosis and C. tropicalis.},
author = {Silva, S{\'{o}}nia and Negri, Melyssa and Henriques, Mariana and Oliveira, Ros{\'{a}}rio and Williams, David W. and Azeredo, Joana},
booktitle = {FEMS Microbiology Reviews},
doi = {10.1111/j.1574-6976.2011.00278.x},
isbn = {0168-6445},
issn = {01686445},
keywords = {Antifungal resistance,Candida species,Candidosis,Epidemiology,Virulence factors},
number = {2},
pages = {288--305},
pmid = {21569057},
title = {{Candida glabrata, Candida parapsilosis and Candida tropicalis: Biology, epidemiology, pathogenicity and antifungal resistance}},
volume = {36},
year = {2012}
}
@article{Mallah2017,
abstract = {The production of new types of genetically modified organisms (GMOs) and the use of products containing or derived from these materials are expanding globally. This poses a challenge in providing cost-effective comprehensive analyses. In this line, the state of art testing approaches rely on a matrix representing the GM events with their corresponding GM markers - DNA elements used in plants' transformation. Accordingly, this study aimed first at constructing an updated and comprehensive matrix of genetic characterization of GM events based on an extensive review of the relevant databases. Inclusive lists of 356 GM markers and 508 events in 29 plant species were compiled and organized into a matrix. The frequency of occurrence of these elements was then determined. Moreover, for the first time, a matrix representing the regulatory status of every compiled GM event was established. Remarkably, numerous inconsistencies were detected among the databases at the levels of nomenclature, events' registry, molecular characterization and regulatory approvals. Both matrices represent a useful tool for comprehensive and cost-effective analyses. The genetic matrix permits designing the most straightforward testing strategy that provides the maximum information about GMOs in a sample in the minimum number of experimental steps. Moreover, the novel regulatory matrix, allows further decreasing the number of required event-specific identification tests by giving higher probabilities to those authorized in the samples' country of origin. Finally, the genetics and regulatory matrices represent the building-block for establishing an inclusive automated database for GMOs which is instrumental for testing laboratories worldwide.},
author = {Mallah, Narmeen and Obeid, Marc and {Abou Sleymane}, Gretta},
doi = {10.1016/j.foodcont.2017.03.053},
issn = {09567135},
journal = {Food Control},
keywords = {DNA,Database,GMOs,Matrix,Regulations},
pages = {52--58},
title = {{Comprehensive matrices for regulatory approvals and genetic characterization of genetically modified organisms}},
volume = {80},
year = {2017}
}
@book{Kuzmin2014a,
abstract = {{\textcopyright} Springer Science+Business Media New York 2014. Genetic interactions occur when mutant alleles of two or more genes collaborate to generate an unusual composite phenotype, one that would not be predicted based on the expected combined effects of the individual mutant alleles. Synthetic Genetic Array (SGA) methodology was developed to automate yeast genetic analysis and enable systematic genetic interaction studies. In its simplest form, SGA consists of a series of replica pinning steps, which enable the construction of haploid double mutants through mating and meiotic recombination. For example, a strain carrying a query mutation, such as a deletion allele of a nonessential gene or a conditional temperature sensitive allele of an essential gene, could be crossed to an input array of yeast mutants, such as the complete set of ∼5,000 viable deletion mutants, to generate an output array of double mutants, that can be scored for genetic interactions based on estimates of cellular fitness derived from colony-size measurements. A simple quantitative measure of genetic interactions can be derived from colony size, which serves as a proxy for fitness. Furthermore, SGA can be applied in a variety of other contexts, such as Synthetic Dosage Lethality (SDL), in which a query mutation is crossed into an array of yeast strains, each of which overexpresses a different gene, thus making use of SGA to probe for gain-of-function phenotypes in specific genetic backgrounds. High-Content Screening (HCS) also integrates SGA to perform genome-wide screens for quantitative analysis of morphological phenotypes or pathway activity based upon fluorescent markers, extending genetic interaction analysis beyond fitness-based measurements. Genetic interaction studies offer insight into gene function, pathway structure, and buffering, and thus a complete genetic interaction network of yeast will generate a global functional wiring diagram for a eukaryotic cell.},
author = {Kuzmin, E. and Sharifpoor, S. and Baryshnikova, A. and Costanzo, M. and Myers, C.L. and Andrews, B.J. and Boone, C.},
booktitle = {Methods in Molecular Biology},
doi = {10.1007/978-1-4939-1363-3_10},
issn = {10643745},
keywords = {Genetic interactions,Genetics,High-content screening,Synthetic dosage lethality,Synthetic genetic array,Yeast},
pages = {143--168},
pmid = {25213244},
title = {{Synthetic genetic array analysis for global mapping of genetic networks in yeast}},
volume = {1205},
year = {2014}
}
@article{McCubrey2015,
abstract = {The EGFR/PI3K/PTEN/Akt/mTORC pathway plays prominent roles in malignant transformation, prevention of apoptosis, drug resistance, cancer initiating cells (CICs) and metastasis. The expression of this pathway is frequently altered in breast and other cancers due to mutations at or aberrant expression of: HER2, EGFR1, PIK3CA, and PTEN as well as other oncogenes and tumor suppressor genes. miRs and epigenetic mechanisms of gene regulation are also important events which regulate this pathway. In some breast cancer cases, mutations at certain components of this pathway (e.g., PIK3CA) are associated with a better prognosis than breast cancers lacking these mutations. The expression of this pathway has been associated with CICs and in some cases resistance to therapeutics. We will review the effects of activation of the EGFR/PI3K/PTEN/Akt/mTORC pathway primarily in breast cancer and development of drug resistance. The targeting of this pathway and other interacting pathways will be discussed as well as clinical trials with novel small molecule inhibitors as well as established drugs that are used to treat other diseases. In this manuscript, we will discuss an inducible EGFR model (v-ERB-B:ER) and its effects on cell growth, cell cycle progression, activation of signal transduction pathways, prevention of apoptosis in hematopoietic, breast and prostate cancer models.},
author = {McCubrey, James A. and Abrams, Stephen L. and Fitzgerald, Timothy L. and Cocco, Lucio and Martelli, Alberto M. and Montalto, Giuseppe and Cervello, Melchiorre and Scalisi, Aurora and Candido, Saverio and Libra, Massimo and Steelman, Linda S.},
doi = {10.1016/j.jbior.2014.09.016},
isbn = {2212-4934 (Electronic)$\backslash$r2212-4926 (Linking)},
issn = {22124926},
journal = {Advances in Biological Regulation},
keywords = {Breast cancer,Cancer stem cells,EGFR,ER,HER2,Hormonal therapy,Targeted therapy,Therapy resistance},
pmid = {25453219},
title = {{Roles of signaling pathways in drug resistance, cancer initiating cells and cancer progression and metastasis}},
year = {2015}
}
@article{Rubin2013,
annote = {doi: 10.1016/j.tibs.2012.10.007},
author = {Rubin, Seth M},
doi = {10.1016/j.tibs.2012.10.007},
issn = {0968-0004},
journal = {Trends in Biochemical Sciences},
month = {jan},
number = {1},
pages = {12--19},
publisher = {Elsevier},
title = {{Deciphering the retinoblastoma protein phosphorylation code}},
url = {https://doi.org/10.1016/j.tibs.2012.10.007},
volume = {38},
year = {2013}
}
@book{Klipp2009,
abstract = {Systems biology is a highly topical discipline at the intersection of biochemistry, cell biology, computer science, and systems engineering. This course book in systems biology is tailored to the needs of advanced students of biology, engineering, and computer science. It has a companion website with solutions to questions in the book, additional chapters, and computer implementations of systems biology models. The book is a follow-up of the very successful Systems Biology in Practice and incorporates the feedback and suggestions of many lecturers worldwide. The interdisciplinary team of acclaimed authors have worked closely together to ensure a comprehensive coverage of the topic in a fluent and compelling style. Further material is available on www.wiley-vch.de/home/systemsbiology Systems Biology in Practice - Praise from the reviews: "...this is one book that I bought for myself as soon as it was published." British Journal of Occupational Therapy "This resource does an admirable job of bringing the readers to a level where they can pursue more advanced study and research." IEEE Engineering in Medicine and Biology Magazine I am confident that biologists everywhere will benefit from having a copy to hand." Theoretical Biology and Medical Modelling},
archivePrefix = {arXiv},
arxivId = {arXiv:1011.1669v3},
author = {Klipp, Edda and Liebermeister, Wolfram and Wierling, Christoph and Kowald, Axel and Lehrach, Hans and Herwig, Ralf},
booktitle = {Time},
doi = {10.3797/scipharm},
eprint = {arXiv:1011.1669v3},
isbn = {3527318747},
issn = {1098-6596},
pmid = {25246403},
title = {{Systems Biology: A Textbook}},
year = {2009}
}
@article{Mazzei2007,
abstract = {A novel bioelectrochemical method for the direct determination of D(-) L(+) lactic acid and of L(-) malic acid in wines is presented. Multienzymatic biosensors were realized for the selective determination of the three analytes: D(-) and L(+) lactic acid were measured by a trienzymatic biosensor based on the catalytic activities of the enzymes L(+) lactate oxidase (LOD), D(-) lactate dehydrogenase (D-LDH) and horseradish peroxidase (HRP); L(-) malic acid was measured by a bienzymatic electrode, realized by coupling the enzymes L(-) malic dehydrogenase (L-MDH) and horseradish peroxidase (HRP). In both cases the enzymes were immobilized on an oxygen selective Clark electrode. The simultaneous determination of the two organic acids can be accomplished either in batch or in a flow injection analysis apparatus using the same biosensors as detectors. The analytical performance of the method, tested in standard aqueous solutions and on real samples of wines, showing high repeatability, short response times and reduced cost of analysis, suggest that the experimental approach here described could be followed to monitor the progress of malolactic fermentation. ?? 2007.},
author = {Mazzei, Franco and Botr{\`{e}}, Francesco and Favero, Gabriele},
doi = {10.1016/j.microc.2007.05.009},
isbn = {0026-265X},
issn = {0026265X},
journal = {Microchemical Journal},
keywords = {Biosensors,Lactic acid,Malic acid,Wine},
number = {1},
pages = {81--86},
title = {{Peroxidase based biosensors for the selective determination of D,L-lactic acid and L-malic acid in wines}},
volume = {87},
year = {2007}
}
@article{Zackrisson2016,
abstract = {The capacity to map traits over large cohorts of individuals – phenomics – lags far behind the explosive development in genomics. For microbes the estimation of growth is the key phenotype because of its link to fitness. We introduce an automated microbial phenomics framework that delivers accurate, precise and highly resolved growth phenotypes at an unprecedented scale. Advancements were achieved through introduction of transmissive scanning hardware and software technology, frequent acquisition of exact colony population size measurements, extraction of population growth rates from growth curves and removal of spatial bias by reference-surface normalization. Our prototype arrangement automatically records and analyzes close to 100,000 growth curves in parallel. We demonstrate the power of the approach by extending and nuancing the known salt-defense biology in baker's yeast. The introduced framework represents a major advance in microbial phenomics by providing high-quality data for extensive cohorts of individuals and generating well-populated and standardized phenomics databases. },
author = {Zackrisson, Martin and Hallin, Johan and Ottosson, Lars-G{\"{o}}ran and Dahl, Peter and Fernandez-Parada, Esteban and L{\"{a}}ndstr{\"{o}}m, Erik and Fernandez-Ricaud, Luciano and Kaferle, Petra and Skyman, Andreas and Stenberg, Simon and Omholt, Stig and Petrovi{\v{c}}, Uro{\v{s}} and Warringer, Jonas and Blomberg, Anders},
doi = {10.1534/g3.116.032342},
issn = {2160-1836},
journal = {G3{\&}{\#}58; Genes|Genomes|Genetics},
number = {9},
pages = {3003--3014},
pmid = {27371952},
title = {{Scan-o-matic: High-Resolution Microbial Phenomics at a Massive Scale}},
url = {http://g3journal.org/lookup/doi/10.1534/g3.116.032342},
volume = {6},
year = {2016}
}
@article{Vahedi2009,
abstract = {External control of a genetic regulatory network is used for the purpose of avoiding undesirable states, such as those associated with a disease. To date, intervention has mainly focused on the external control of probabilistic Boolean networks via the associated discrete-time discrete-space Markov processes. Implementation of an intervention policy derived for probabilistic Boolean networks requires nearly continuous observation of the underlying biological system since precise application requires the observation of all transitions. In medical applications, as in many engineering problems, the process is sampled at discrete time intervals and a decision to intervene or not must be made at each sample point. In this work, sampling-rate-dependent probabilistic Boolean network is proposed as an extension of probabilistic Boolean network. The proposed framework is capable of capturing the sampling rate of the underlying system. {\textcopyright} 2009 Elsevier Ltd. All rights reserved.},
author = {Vahedi, Golnaz and Faryabi, Babak and Chamberland, Jean Francois and Datta, Aniruddha and Dougherty, Edward R.},
doi = {10.1016/j.jtbi.2009.08.026},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Vahedi et al. - 2009 - Sampling-rate-dependent probabilistic Boolean networks.pdf:pdf},
isbn = {0022-5193},
issn = {00225193},
journal = {Journal of Theoretical Biology},
keywords = {Gene regulatory network,Intervention,Optimal control,Probabilistic Boolean network},
pmid = {19716832},
title = {{Sampling-rate-dependent probabilistic Boolean networks}},
year = {2009}
}
@article{Yin2014a,
abstract = {We demonstrate CRISPR-Cas9-mediated correction of a Fah mutation in hepatocytes in a mouse model of the human disease hereditary tyrosinemia. Delivery of components of the CRISPR-Cas9 system by hydrodynamic injection resulted in initial expression of the wild-type Fah protein in ∼1/250 liver cells. Expansion of Fah-positive hepatocytes rescued the body weight loss phenotype. Our study indicates that CRISPR-Cas9-mediated genome editing is possible in adult animals and has potential for correction of human genetic diseases.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Yin, Hao and Xue, Wen and Chen, Sidi and Bogorad, Roman L and Benedetti, Eric and Grompe, Markus and Koteliansky, Victor and Sharp, Phillip A and Jacks, Tyler and Anderson, Daniel G},
doi = {10.1038/nbt.2884},
eprint = {NIHMS150003},
isbn = {1546-1696 (Electronic)$\backslash$r1087-0156 (Linking)},
issn = {1087-0156},
journal = {Nature Biotechnology},
number = {6},
pages = {551--553},
pmid = {24681508},
title = {{Genome editing with Cas9 in adult mice corrects a disease mutation and phenotype}},
url = {http://www.nature.com/doifinder/10.1038/nbt.2884},
volume = {32},
year = {2014}
}
@article{Qin2008,
abstract = {Several immobilized enzyme-based electrochemical biosensors for glutamate$\backslash$ndetection have been developed over the last decade. In this review, we compare first and$\backslash$nsecond generation sensors. Structures, working mechanisms, interference prevention, in$\backslash$nvitro detection characteristics and in vivo performance are summarized here for those$\backslash$nsensors that have successfully detected brain glutamate in vivo. In brief, first generation$\backslash$nsensors have a simpler structure and are faster in glutamate detection. They also show a$\backslash$nbetter sensitivity to glutamate during calibration in vitro. For second generation sensors,$\backslash$nbesides their less precise detection, their fabrication is difficult to reproduce, even with a$\backslash$nsemi-automatic dip-coater. Both generations of sensors can detect glutamate levels in vivo,$\backslash$nbut the reported basal levels are different. In general, second generation sensors detect higher$\backslash$nbasal levels of glutamate compared with the results obtained from first generation sensors.$\backslash$nHowever, whether the detected glutamate is indeed from synaptic sources is an issue that$\backslash$nneeds further attention.},
author = {Qin, Si and {Van Der Zeyden}, Miranda and Oldenziel, Weite H. and Cremers, Thomas I F H and Westerink, Ben H C},
doi = {10.3390/s8116860},
isbn = {3150363837},
issn = {14248220},
journal = {Sensors},
keywords = {First generation biosensor,Glutamate,In vivo detection,Second generation biosensor},
number = {11},
pages = {6860--6884},
title = {{Microsensors for in vivo measurement of glutamate in brain tissue}},
volume = {8},
year = {2008}
}
@article{Li1993,
abstract = {Many of the actions of receptor tyrosine kinases are mediated by the protein Ras, including the activation of various downstream serine/threonine kinases and the stimulation of growth and differentiation. The human protein Grb2 binds to ligand-activated growth factor receptors and downstream effector proteins through its Src-homology (SH) domains SH2 and SH3, respectively, and like its homologue from Caenorhabditis elegans, Sem-5, apparently forms part of a highly conserved pathway by which these receptors can control Ras activity. Here we show that the SH3 domains of Grb2 bind to the carboxy-terminal part of hSos1, the human homologue of the Drosophila guanine-nucleotide-releasing factor for Ras, which is essential for control of Ras activity by epidermal growth factor receptor and sevenless. Moreover, a synthetic 10-amino-acid peptide containing the sequence PPVPPR specifically blocks the interaction. These results indicate that the Grb2/hSos1 complex couples activated EGF receptor to Ras signalling.},
author = {Li, N. and Batzer, A. and Daly, R. and Yajnik, V. and Skolnik, E. and Chardin, P. and Bar-Sagi, D. and Margolis, B. and Schlessinger, J.},
doi = {10.1038/363085a0},
isbn = {0028-0836 (Print)$\backslash$n0028-0836 (Linking)},
issn = {00280836},
journal = {Nature},
pmid = {8479541},
title = {{Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling}},
year = {1993}
}
@article{Chen2008,
abstract = {BACKGROUND: Inflammation is a hallmark of many human diseases. Elucidating the mechanisms underlying systemic inflammation has long been an important topic in basic and clinical research. When primary pathogenetic events remains unclear due to its immense complexity, construction and analysis of the gene regulatory network of inflammation at times becomes the best way to understand the detrimental effects of disease. However, it is difficult to recognize and evaluate relevant biological processes from the huge quantities of experimental data. It is hence appealing to find an algorithm which can generate a gene regulatory network of systemic inflammation from high-throughput genomic studies of human diseases. Such network will be essential for us to extract valuable information from the complex and chaotic network under diseased conditions.$\backslash$n$\backslash$nRESULTS: In this study, we construct a gene regulatory network of inflammation using data extracted from the Ensembl and JASPAR databases. We also integrate and apply a number of systematic algorithms like cross correlation threshold, maximum likelihood estimation method and Akaike Information Criterion (AIC) on time-lapsed microarray data to refine the genome-wide transcriptional regulatory network in response to bacterial endotoxins in the context of dynamic activated genes, which are regulated by transcription factors (TFs) such as NF-kappaB. This systematic approach is used to investigate the stochastic interaction represented by the dynamic leukocyte gene expression profiles of human subject exposed to an inflammatory stimulus (bacterial endotoxin). Based on the kinetic parameters of the dynamic gene regulatory network, we identify important properties (such as susceptibility to infection) of the immune system, which may be useful for translational research. Finally, robustness of the inflammatory gene network is also inferred by analyzing the hubs and "weak ties" structures of the gene network.$\backslash$n$\backslash$nCONCLUSION: In this study, Data mining and dynamic network analyses were integrated to examine the gene regulatory network in the inflammatory response system. Compared with previous methodologies reported in the literatures, the proposed gene network perturbation method has shown a great improvement in analyzing the systemic inflammation.},
author = {Chen, Bor-Sen and Yang, Shih-Kuang and Lan, Chung-Yu and Chuang, Yung-Jen},
doi = {10.1186/1755-8794-1-46},
isbn = {1755-8794 (Electronic)$\backslash$r1755-8794 (Linking)},
issn = {1755-8794},
journal = {BMC Medical Genomics},
pmid = {18823570},
title = {{A systems biology approach to construct the gene regulatory network of systemic inflammation via microarray and databases mining}},
year = {2008}
}
@article{Jinek2012,
abstract = {Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems provide bacteria and archaea with adaptive immunity against viruses and plasmids by using CRISPR RNAs (crRNAs) to guide the silencing of invading nucleic acids. We show here that in a subset of these systems, the mature crRNA that is base-paired to trans-activating crRNA (tracrRNA) forms a two-RNA structure that directs the CRISPR-associated protein Cas9 to introduce double-stranded (ds) breaks in target DNA. At sites complementary to the crRNA-guide sequence, the Cas9 HNH nuclease domain cleaves the complementary strand, whereas the Cas9 RuvC-like domain cleaves the noncomplementary strand. The dual-tracrRNA:crRNA, when engineered as a single RNA chimera, also directs sequence-specific Cas9 dsDNA cleavage. Our study reveals a family of endonucleases that use dual-RNAs for site-specific DNA cleavage and highlights the potential to exploit the system for RNA-programmable genome editing.},
archivePrefix = {arXiv},
arxivId = {38},
author = {Jinek, Martin and Chylinski, Krzysztof and Fonfara, Ines and Hauer, Michael and Doudna, Jennifer A and Charpentier, Emmanuelle},
doi = {10.1126/science.1225829},
eprint = {38},
isbn = {6212011575},
issn = {0036-8075},
journal = {Science (New York, N.Y.)},
keywords = {Bacteriophages,Bacteriophages: immunology,Base Sequence,DNA Breaks, Double-Stranded,DNA Cleavage,Deoxyribonucleases, Type II Site-Specific,Deoxyribonucleases, Type II Site-Specific: chemist,Deoxyribonucleases, Type II Site-Specific: genetic,Deoxyribonucleases, Type II Site-Specific: metabol,Inverted Repeat Sequences,Molecular Sequence Data,Nucleic Acid Conformation,Plasmids,Plasmids: metabolism,RNA,RNA: chemistry,RNA: metabolism,Streptococcus pyogenes,Streptococcus pyogenes: enzymology,Streptococcus pyogenes: physiology},
number = {August},
pages = {816--822},
pmid = {22745249},
title = {{A Programmable Dual-RNA – Guided DNA Endonuclease in Adaptice Bacterial Immunity}},
url = {http://science.sciencemag.org/content/337/6096/816.abstract},
volume = {337},
year = {2012}
}
@article{Kato2012,
abstract = {A method for a widely targeted analysis was developed for the metabolic profiling of yeast central metabolism. The widely targeted method consists of 2 analyses, namely, gas chromatography-quadrupole-mass spectrometry (GC-Q-MS) operated in selected ion monitoring mode with 25m/z channels, and liquid chromatography triple-stage quadrupole (LC-QqQ)-MS operated in multiple reaction monitoring mode. This platform was set up to identify and quantify preselected 99 compounds, including sugars, sugar phosphates, organic acids, amino acids, and cofactors. The method showed good sensitivity and a wide dynamic range. For example, limits of detection for lactate and l-phenylalanine were 1.4fmol and 2.0fmol, respectively. The dynamic ranges for GC-Q-MS analysis and LC-QqQ-MS analysis were approximately 102-105 and 103-104, respectively. The metabolite profiles of 2 yeast strains, YPH499 and BY4741, under glucose-fermenting conditions were compared using the developed method. Although YPH499 and BY4741 were derived from an identical experimental strain, the profiling analysis successfully revealed a variation in metabolic phenotypes among experimental yeast strains demonstrating that the widely targeted method could be a robust and useful method for the investigation of metabolic phenotypes of Saccharomyces cerevisiae. ?? 2012 The Society for Biotechnology, Japan.},
author = {Kato, Hiroko and Izumi, Yoshihiro and Hasunuma, Tomohisa and Matsuda, Fumio and Kondo, Akihiko},
doi = {10.1016/j.jbiosc.2011.12.013},
isbn = {1389-1723},
issn = {13891723},
journal = {Journal of Bioscience and Bioengineering},
keywords = {Central metabolism,Gas chromatography,Liquid chromatography,Quadrupole mass spectrometer,Saccharomyces cerevisiae,Widely targeted metabolic profiling analysis},
number = {5},
pages = {665--673},
pmid = {22280965},
title = {{Widely targeted metabolic profiling analysis of yeast central metabolites}},
volume = {113},
year = {2012}
}
@article{Swainston2009,
abstract = {SUMMARY: The Systems Biology Markup Language (SBML) is an established community XML format for the markup of biochemical models. With the introduction of SBML level 2 version 3, specific model entities, such as species or reactions, can now be annotated using ontological terms. These annotations, which are encoded using the resource description framework (RDF), provide the facility to specify definite terms to individual components, allowing software to unambiguously identify such components and thus link the models to existing data resources. libSBML is an application programming interface library for the manipulation of SBML files. While libSBML provides the facilities for reading and writing such annotations from and to models, it is beyond the scope of libSBML to provide interpretation of these terms. The libAnnotationSBML library introduced here acts as a layer on top of libSBML linking SBML annotations to the web services that describe these ontological terms. Two applications that use this library are described: SbmlSynonymExtractor finds name synonyms of SBML model entities and SbmlReactionBalancer checks SBML files to determine whether specifed reactions are elementally balanced.},
author = {Swainston, Neil and Mendes, Pedro},
doi = {10.1093/bioinformatics/btp392},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Swainston, Mendes - 2009 - libAnnotationSBML A library for exploiting SBML annotations.pdf:pdf},
isbn = {1367-4811 (Linking)},
issn = {13674803},
journal = {Bioinformatics},
number = {17},
pages = {2292--2293},
pmid = {19561017},
title = {{libAnnotationSBML: A library for exploiting SBML annotations}},
volume = {25},
year = {2009}
}
@article{Hucka2003,
abstract = {MOTIVATION: Molecular biotechnology now makes it possible to build elaborate systems models, but the systems biology community needs information standards if models are to be shared, evaluated and developed cooperatively. RESULTS: We summarize the Systems Biology Markup Language (SBML) Level 1, a free, open, XML-based format for representing biochemical reaction networks. SBML is a software-independent language for describing models common to research in many areas of computational biology, including cell signaling pathways, metabolic pathways, gene regulation, and others. AVAILABILITY: The specification of SBML Level 1 is freely available from http://www.sbml.org/},
author = {Hucka, M. and Finney, A. and Sauro, H. M. and Bolouri, H. and Doyle, J. C. and Kitano, H. and Arkin, A. P. and Bornstein, B. J. and Bray, D. and Cornish-Bowden, A. and Cuellar, A. A. and Dronov, S. and Gilles, E. D. and Ginkel, M. and Gor, V. and Goryanin, I. I. and Hedley, W. J. and Hodgman, T. C. and Hofmeyr, J. H. and Hunter, P. J. and Juty, N. S. and Kasberger, J. L. and Kremling, A. and Kummer, U. and {Le Nov{\`{e}}re}, N. and Loew, L. M. and Lucio, D. and Mendes, P. and Minch, E. and Mjolsness, E. D. and Nakayama, Y. and Nelson, M. R. and Nielsen, P. F. and Sakurada, T. and Schaff, J. C. and Shapiro, B. E. and Shimizu, T. S. and Spence, H. D. and Stelling, J. and Takahashi, K. and Tomita, M. and Wagner, J. and Wang, J.},
doi = {10.1093/bioinformatics/btg015},
isbn = {1367-4803 (Print)$\backslash$r1367-4803 (Linking)},
issn = {13674803},
journal = {Bioinformatics},
pmid = {12611808},
title = {{The systems biology markup language (SBML): A medium for representation and exchange of biochemical network models}},
year = {2003}
}
@article{DeSantis2017,
abstract = {Within the frame of the EU-funded MARLON project, background data were reviewed to explore the possibility of measuring health indicators during post-market monitoring for potential effects of feeds, particularly genetically modified (GM) feeds, on livestock animal health, if applicable. Four case studies (CSs) of potential health effects on livestock were framed and the current knowledge of a possible effect of GM feed was reviewed. Concerning allergenicity (CS-1), there are no case-reports of allergic reactions or immunotoxic effects resulting from GM feed consumption as compared with non-GM feed. The likelihood of horizontal gene transfer (HGT; CS-2) of GMO-related DNA to different species is not different from that for other DNA and is unlikely to raise health concerns. Concerning mycotoxins (CS-3), insect-resistant GM maize may reduce fumonisins contamination as a health benefit, yet other Fusarium toxins and aflatoxins show inconclusive results. For nutritionally altered crops (CS-4), the genetic modifications applied lead to compositional changes which require special considerations of their nutritional impacts. No health indicators were thus identified except for possible beneficial impacts of reduced mycotoxins and nutritional enhancement. More generally, veterinary health data should ideally be linked with animal exposure information so as to be able to establish cause-effect relationships.},
author = {{De Santis}, Barbara and Stockhofe, Norbert and Wal, Jean-Michel and Weesendorp, Eefke and Lall{\`{e}}s, Jean-Paul and van Dijk, Jeroen and Kok, Esther and {De Giacomo}, Marzia and Einspanier, Ralf and Onori, Roberta and Brera, Carlo and Bikker, Paul and van der Meulen, Jan and Gijs, Kleter},
doi = {10.1016/j.fct.2017.08.033},
issn = {02786915},
journal = {Food and Chemical Toxicology},
pmid = {28859885},
title = {{Case studies on genetically modified organisms (GMOs): Potential risk scenarios and associated health indicators}},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0278691517304842},
year = {2017}
}
@article{Shelly1998,
abstract = {The ErbB signaling network consists of four transmembrane receptor tyrosine kinases and more than a dozen ligands sharing an epidermal growth factor (EGF) motif. The multiplicity of ErbB-specific ligands is incompletely understood in terms of signal specificity because all ErbB molecules signal through partially overlapping pathways. Here we addressed the action of epiregulin, a recently isolated ligand of ErbB-1. By employing a set of factor-dependent cell lines engineered to express individual ErbBs or their combinations, we found that epiregulin is the broadest specificity EGF-like ligand so far characterized: not only does it stimulate homodimers of both ErbB-1 and ErbB-4, it also activates all possible heterodimeric ErbB complexes. Consistent with its relaxed selectivity, epiregulin binds the various receptor combinations with an affinity that is approximately 100-fold lower than the affinity of ligands with more stringent selectivity, including EGF. Nevertheless, epiregulin's action upon most receptor combinations transmits a more potent mitogenic signal than does EGF. This remarkable discrepancy between binding affinity and bioactivity is permitted by a mechanism that prevents receptor down-regulation, and results in a weak, but prolonged, state of receptor activation.},
author = {Shelly, Maya and Pinkas-Kramarski, Ronit and Guarino, Bradley C. and Waterman, Hadassa and Wang, Ling Mei and Lyass, Ljuba and Alimandi, Mauricio and Kuo, Angera and Bacus, Sarah S. and Pierce, Jacalyn H. and Andrews, Glenn C. and Yarden, Yosef},
doi = {10.1074/jbc.273.17.10496},
isbn = {0021-9258 (Print)$\backslash$r0021-9258 (Linking)},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {9553109},
title = {{Epiregulin is a potent Pan-ErbB ligand that preferentially activates heterodimeric receptor complexes}},
year = {1998}
}
@misc{Rollie2012a,
abstract = {Synthetic Biology offers qualitatively new perspectives on the benefits of industrially harnessed biological processes. The ability to modify and reprogramme natural biology increases the scope of tailored bioprocesses and yields attractive prospects beyond conventional Biotechnology. The present review summarises the major achievements and categorises them according to a hierarchy of system levels. Similar structures are known in the engineering sciences and might prove useful for the future development of Synthetic Biology. The hierarchy encompasses several levels of detail. Biological (macro-)molecules present the most detailed level (parts), followed by compartmentalised or non-compartmentalised modules (devices). In the next level, parts and devices are combined into functional cells and further into cellular communities. The manifold interactions between biological entities of the same hierarchical level or between different levels are accounted for by networks, primarily metabolic pathways and regulatory circuits. Networks of different types are represented as a superordinate hierarchical level that achieves full system integration. On all these levels, extensive and sound scientific foundations exist regarding experimental but also theoretical methods. These have led to diverse manifestations of Synthetic Biology on the parts and devices levels. Investigations involving synthetic components on the systems scale represent the most difficult and remain limited in number. A main challenge lies with the quantitative prediction of interactions between different entities across different scales. Systems-theoretical approaches provide important tools to analyse complex biological behaviour and can support the design of artificial biological systems. A promising strategy is seen in an efficient modularisation that reduces biological systems to a limited set of functional modules with well-characterised interfaces. For the design of synthetic biological systems the interactions across these interfaces should be standardised to reduce complexity. Yet, the identification of modules and standardised interaction routes remains a non-trivial problem. Furthermore, an appropriate platform that efficiently describes replication and evolutionary processes has to be developed in order to extend the achievements of Synthetic Biology into designed biological processes. {\textcopyright} 2011 Elsevier Ltd.},
author = {Rolli{\'{e}}, Sascha and Mangold, Michael and Sundmacher, Kai},
booktitle = {Chemical Engineering Science},
doi = {10.1016/j.ces.2011.10.068},
isbn = {0009-2509},
issn = {00092509},
keywords = {Biomolecular Engineering,Biosystems Engineering,Cell Biology,Process synthesis,Synthetic Biology,Systems Biology},
pmid = {20233039},
title = {{Designing biological systems: Systems Engineering meets Synthetic Biology}},
year = {2012}
}
@misc{Arkin2014,
abstract = {The past 20 years have seen many advances in our understanding of protein-protein interactions (PPIs) and how to target them with small-molecule therapeutics. In 2004, we reviewed some early successes; since then, potent inhibitors have been developed for diverse protein complexes, and compounds are now in clinical trials for six targets. Surprisingly, many of these PPI clinical candidates have efficiency metrics typical of "lead-like" or "drug-like" molecules and are orally available. Successful discovery efforts have integrated multiple disciplines and make use of all the modern tools of target-based discovery - structure, computation, screening, and biomarkers. PPIs become progressively more challenging as the interfaces become more complex, i.e., as binding epitopes are displayed on primary, secondary, or tertiary structures. Here, we review the last 10 years of progress, focusing on the properties of PPI inhibitors that have advanced to clinical trials and prospects for the future of PPI drug discovery.},
archivePrefix = {arXiv},
arxivId = {arXiv:1011.1669v3},
author = {Arkin, Michelle R. and Tang, Yinyan and Wells, James A.},
booktitle = {Chemistry and Biology},
doi = {10.1016/j.chembiol.2014.09.001},
eprint = {arXiv:1011.1669v3},
isbn = {1074-5521},
issn = {10745521},
number = {9},
pages = {1102--1114},
pmid = {25237857},
title = {{Small-molecule inhibitors of protein-protein interactions: Progressing toward the reality}},
volume = {21},
year = {2014}
}
@article{FuhsMonika;HamielDaniel;MossDon;PeperE.&Sella2005,
author = {{Fuhs, Monika; Hamiel, Daniel; Moss, Don; Peper, E. {\&} Sella}, G.},
doi = {10.1525/jer.2011.6.1.toc},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Fuhs, Monika Hamiel, Daniel Moss, Don Peper, E. {\&} Sella - 2005 - Table of contents.pdf:pdf},
issn = {1556-2646},
journal = {Psychophysiology Today},
number = {1},
pages = {1--36},
pmid = {21460580},
title = {{Table of contents.}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/21460580},
volume = {6},
year = {2005}
}
@article{Sanchez2001,
abstract = {This manuscript focuses on the formal analysis of the gap-gene network involved in Drosophila segmentation. The gap genes are expressed in defined domains along the anterior-posterior axis of the embryo, as a response to asymmetric maternal information in the oocyte. Though many of the individual interactions among maternal and gap genes are reasonably well understood, we still lack a thorough understanding of the dynamic behavior of the system as a whole. Based on a generalized logical formalization, the present analysis leads to the delineation of: (1) the minimal number of distinct, qualitative, functional levels associated with each of the key regulatory factors (the three maternal Bcd, Hb and Cad products, and the four gap Gt, Hb, Kr and Kni products); (2) the most crucial interactions and regulatory circuits of the earliest stages of the segmentation process; (3) the ordering of different regulatory interactions governed by each of these products according to corresponding concentration scales; and (4) the role of gap-gene cross-interactions in the transformation of graded maternal information into discrete gap-gene expression domains. The proposed model allows not only the qualitative reproduction of the patterns of gene expression characterized experimentally, but also the simulation and prediction of single and multiple mutant phenotypes.},
author = {Sanchez, L and Thieffry, D},
doi = {10.1006/jtbi.2001.2335},
isbn = {0022-5193 (Print)$\backslash$r0022-5193 (Linking)},
journal = {J Theor Biol},
keywords = {*Computer Simulation,*Genes, Insect,*Genes, Regulator,*Models, Genetic,Animals,Body Patterning/genetics,Drosophila melanogaster/embryology/*genetics,Egg Proteins/metabolism,Female,Gene Expression,Mutation,Oocytes/metabolism,Organizers, Embryonic,Phenotype},
pmid = {11419955},
title = {{A logical analysis of the Drosophila gap-gene system}},
year = {2001}
}
@article{Hoehndorf2011,
abstract = {Phenotypes are investigated in model organisms to understand and reveal the molecular mechanisms underlying disease. Phenotype ontologies were developed to capture and compare phenotypes within the context of a single species. Recently, these ontologies were augmented with formal class definitions that may be utilized to integrate phenotypic data and enable the direct comparison of phenotypes between different species. We have developed a method to transform phenotype ontologies into a formal representation, combine phenotype ontologies with anatomy ontologies, and apply a measure of semantic similarity to construct the PhenomeNET cross-species phenotype network. We demonstrate that PhenomeNET can identify orthologous genes, genes involved in the same pathway and gene-disease associations through the comparison of mutant phenotypes. We provide evidence that the Adam19 and Fgf15 genes in mice are involved in the tetralogy of Fallot, and, using zebrafish phenotypes, propose the hypothesis that the mammalian homologs of Cx36.7 and Nkx2.5 lie in a pathway controlling cardiac morphogenesis and electrical conductivity which, when defective, cause the tetralogy of Fallot phenotype. Our method implements a whole-phenome approach toward disease gene discovery and can be applied to prioritize genes for rare and orphan diseases for which the molecular basis is unknown.},
author = {Hoehndorf, Robert and Schofield, Paul N. and Gkoutos, Georgios V.},
doi = {10.1093/nar/gkr538},
file = {:Users/ozlem/Documents/text mining papers to read/gkr538.pdf:pdf},
isbn = {1362-4962 (Electronic)$\backslash$n0305-1048 (Linking)},
issn = {03051048},
journal = {Nucleic Acids Research},
number = {18},
pmid = {21737429},
title = {{PhenomeNET: A whole-phenome approach to disease gene discovery}},
volume = {39},
year = {2011}
}
@article{Ekins2007,
abstract = {Pharmacology over the past 100 years has had a rich tradition of scientists with the ability to form qualitative or semi-quantitative relations between molecular structure and activity in cerebro. To test these hypotheses they have consistently used traditional pharmacology tools such as in vivo and in vitro models. Increasingly over the last decade however we have seen that computational (in silico) methods have been developed and applied to pharmacology hypothesis development and testing. These in silico methods include databases, quantitative structure-activity relationships, pharmacophores, homology models and other molecular modeling approaches, machine learning, data mining, network analysis tools and data analysis tools that use a computer. In silico methods are primarily used alongside the generation of in vitro data both to create the model and to test it. Such models have seen frequent use in the discovery and optimization of novel molecules with affinity to a target, the clarification of absorption, distribution, metabolism, excretion and toxicity properties as well as physicochemical characterization. The aim of this review is to illustrate some of the in silico methods for pharmacology that are used in drug discovery. Further applications of these methods to specific targets and their limitations will be discussed in the second accompanying part of this review.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Ekins, S and Mestres, J and Testa, B},
doi = {10.1038/sj.bjp.0707305},
eprint = {NIHMS150003},
isbn = {0007-1188 (Print)},
issn = {00071188},
journal = {British Journal of Pharmacology},
number = {1},
pages = {9--20},
pmid = {17549047},
title = {{{\textless}i{\textgreater}In silico{\textless}/i{\textgreater} pharmacology for drug discovery: methods for virtual ligand screening and profiling}},
url = {http://doi.wiley.com/10.1038/sj.bjp.0707305},
volume = {152},
year = {2007}
}
@article{Yu1995,
abstract = {Cytokines and growth factors induce tyrosine phosphorylation of signal transducers and activators of transcription (STATs) that directly activate gene expression. Cells stably transformed by the Src oncogene tyrosine kinase were examined for STAT protein activation. Assays of electrophoretic mobility, DNA-binding specificity, and antigenicity indicated that Stat3 or a closely related STAT family member was constitutively activated by the Src oncoprotein. Induction of this DNA-binding activity was accompanied by tyrosine phosphorylation of Stat3 and correlated with Src transformation. These findings demonstrate that Src can activate STAT signaling pathways and raise the possibility that Stat3 contributes to oncogenesis by Src.},
author = {Yu, Chao Lan and Meyer, Debra J. and Campbell, George S. and Larner, Andrew C. and Carter-Su, Christin and Schwartz, Jessica and Jove, Richard},
doi = {10.1126/science.7541555},
isbn = {0036-8075 (Print)$\backslash$r0036-8075 (Linking)},
issn = {00368075},
journal = {Science},
pmid = {7541555},
title = {{Enhanced DNA-binding activity of a stat3-related protein in cells transformed by the Src oncoprotein}},
year = {1995}
}
@article{Kanehisa2008a,
abstract = {KEGG (http://www.genome.jp/kegg/) is a database of biological systems that integrates genomic, chemical and systemic functional information. KEGG provides a reference knowledge base for linking genomes to life through the process of PATHWAY mapping, which is to map, for example, a genomic or transcriptomic content of genes to KEGG reference pathways to infer systemic behaviors of the cell or the organism. In addition, KEGG provides a reference knowledge base for linking genomes to the environment, such as for the analysis of drug-target relationships, through the process of BRITE mapping. KEGG BRITE is an ontology database representing functional hierarchies of various biological objects, including molecules, cells, organisms, diseases and drugs, as well as relationships among them. KEGG PATHWAY is now supplemented with a new global map of metabolic pathways, which is essentially a combined map of about 120 existing pathway maps. In addition, smaller pathway modules are defined and stored in KEGG MODULE that also contains other functional units and complexes. The KEGG resource is being expanded to suit the needs for practical applications. KEGG DRUG contains all approved drugs in the US and Japan, and KEGG DISEASE is a new database linking disease genes, pathways, drugs and diagnostic markers.},
author = {Kanehisa, Minoru and Araki, Michihiro and Goto, Susumu and Hattori, Masahiro and Hirakawa, Mika and Itoh, Masumi and Katayama, Toshiaki and Kawashima, Shuichi and Okuda, Shujiro and Tokimatsu, Toshiaki and Yamanishi, Yoshihiro},
doi = {10.1093/nar/gkm882},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Kanehisa et al. - 2008 - KEGG for linking genomes to life and the environment(2).pdf:pdf},
isbn = {1362-4962 (Electronic)$\backslash$r0305-1048 (Linking)},
issn = {03051048},
journal = {Nucleic Acids Research},
number = {SUPPL. 1},
pages = {480--484},
pmid = {18077471},
title = {{KEGG for linking genomes to life and the environment}},
volume = {36},
year = {2008}
}
@article{Santi2010,
abstract = {Akt is involved in the regulation of diverse cellular functions such as cell proliferation, energy metabolism, and apoptosis. Although three Akt isoforms are known, the function of each isoform is poorly understood. To gain a better understanding of each Akt isoform, we examined the subcellular localization and expression of each isoform in transformed and nontransformed cells. Akt1 was localized in the cytoplasm, which is in agreement with the currently accepted model that cytoplasmic Akt is translocated and activated at the inner leaflet of the plasma membrane. Interestingly, HEK-293 and HEK-293T cells contained Akt1 in the nucleus and cytoplasm, respectively, suggesting that SV40 T-antigen plays a crucial role in the cytoplasmic localization and activation of Akt1 in HEK-293T. Akt2 was colocalized with the mitochondria, while Akt3 was localized in both the nucleus and nuclear membrane. The subcellular localization of the Akt isoforms was not substantially altered in response to ionizing radiation or EGF. Furthermore, the ablation of one Akt isoform by small interfering RNA (siRNA) did not alter the subcellular location of the remaining isoforms, suggesting that the major function of one isoform is not compensated for by other isoforms. Together, our data support the notion that Akt2 and Akt3 are regulated at the mitochondrial and nuclear membranes, respectively. The mitochondrial localization of Akt2 raises the possibility that this isoform may be involved in both glucose-based energy metabolism and suppression of apoptosis, two Akt functions previously identified with anti-pan-Akt antibodies.},
author = {Santi, S. A. and Lee, H.},
doi = {10.1152/ajpcell.00375.2009},
isbn = {1522-1563 (Electronic)$\backslash$r0363-6143 (Linking)},
issn = {0363-6143},
journal = {AJP: Cell Physiology},
pmid = {20018949},
title = {{The Akt isoforms are present at distinct subcellular locations}},
year = {2010}
}
@article{Andl2004,
abstract = {The epidermal growth factor receptor (EGFR) activates several signaling cascades in response to epidermal growth factor stimulation. One of these signaling events involves tyrosine phosphorylation of signal transducer and activator of transcription (STAT), whereas another involves activation of the phosphatidylinositol 3-OH kinase pathway. Two possibilities for STAT activation exist: a janus kinase (JAK)-dependent and a JAK-independent mechanism. Herein, we demonstrate that EGFR overexpression in primary esophageal keratinocytes activates STAT in a JAK-dependent fashion with the functional consequence of enhanced cell migration, which can be abolished by use of a JAK-specific inhibitor, AG-490. We determined the mechanisms underlying the signal transduction pathway responsible for increased cell migration. Stimulation of EGFR induces Tyr701 phosphorylation of STAT1 and initiates complex formation of STAT1 and STAT3 with JAK1 and JAK2. Thereafter, the STATs translocate to the nucleus within 15 min. In addition, we found that activation of this signaling pathway results in matrix metalloproteinase-1 (MMP-1) activity. By contrast, Akt activation does not impact the EGFR-STATs-JAKs complex formation and nuclear translocation of the STATs with subsequent MMP-1 activity, although Akt activation may contribute to cell migration through an independent mechanism. Taken together, we find that the recruitment of the STAT-JAK complex by EGFR is responsible for keratinocyte migration that, in turn, might be mediated by MMP-1 activation.},
annote = {doi: 10.1152/ajpgi.00253.2004},
author = {Andl, Claudia D and Mizushima, Takaaki and Oyama, Kenji and Bowser, Mark and Nakagawa, Hiroshi and Rustgi, Anil K},
doi = {10.1152/ajpgi.00253.2004},
issn = {0193-1857},
journal = {American Journal of Physiology-Gastrointestinal and Liver Physiology},
month = {dec},
number = {6},
pages = {G1227--G1237},
publisher = {American Physiological Society},
title = {{EGFR-induced cell migration is mediated predominantly by the JAK-STAT pathway in primary esophageal keratinocytes}},
url = {https://doi.org/10.1152/ajpgi.00253.2004},
volume = {287},
year = {2004}
}
@article{Morris1998,
abstract = {A novel and robust automated docking method that predicts the bound conformations of flexible ligands to macromolecular targets has been developed and tested, in combination with a new scoring function that estimates the free energy change upon binding. Interestingly, this method applies a Lamarckian model of genetics, in which environmental adaptations of an individual's phenotype are reverse transcribed into its genotype and become {\v{Z}} . heritable traits sic . We consider three search methods, Monte Carlo simulated annealing, a traditional genetic algorithm, and the Lamarckian genetic algorithm, and compare their performance in dockings of seven protein᎐ligand test systems having known three-dimensional structure. We show that both the traditional and Lamarckian genetic algorithms can handle ligands with more degrees of freedom than the simulated annealing method used in earlier versions of AUTODOCK, and that the Lamarckian genetic algorithm is the most efficient, reliable, and successful of the three. The empirical free energy function was calibrated using a set of 30 structurally known protein᎐ligand complexes with experimentally determined binding constants. Linear regression analysis of the observed binding constants in terms of a wide variety of structure-derived molecular properties was performed. The final model had a residual standard y1 {\v{Z}} y1 . error of 9.11 kJ mol 2.177 kcal mol and was chosen as the new energy},
author = {Morris, Garrett M. and Goodsell, David S. and Halliday, Robert S. and Huey, Ruth and Hart, William E. and Belew, Richard K. and Olson, Arthur J.},
doi = {10.1002/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B},
isbn = {0192-8651},
issn = {0192-8651},
journal = {Journal of Computational Chemistry},
number = {14},
pages = {1639--1662},
pmid = {2626},
title = {{Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function}},
url = {http://doi.wiley.com/10.1002/{\%}28SICI{\%}291096-987X{\%}2819981115{\%}2919{\%}3A14{\%}3C1639{\%}3A{\%}3AAID-JCC10{\%}3E3.0.CO{\%}3B2-B},
volume = {19},
year = {1998}
}
@article{Langmead2009,
abstract = {Bowtie is an ultrafast, memory-efficient alignment program for aligning short DNA sequence reads to large genomes. For the human genome, Burrows-Wheeler indexing allows Bowtie to align more than 25 million reads per CPU hour with a memory footprint of approximately 1.3 gigabytes. Bowtie extends previous Burrows-Wheeler techniques with a novel quality-aware backtracking algorithm that permits mismatches. Multiple processor cores can be used simultaneously to achieve even greater alignment speeds. Bowtie is open source http://bowtie.cbcb.umd.edu.},
author = {Langmead, Ben and Trapnell, Cole and Pop, Mihai and Salzberg, Steven L},
doi = {10.1186/gb-2009-10-3-r25},
journal = {Genome biology},
number = {10},
pages = {R25},
title = {{Bowtie: An ultrafast memory-efficient short read aligner. [http://bowtie.cbcb.umd.edu/]}},
url = {https://genomebiology.biomedcentral.com/articles/10.1186/gb-2009-10-3-r25},
year = {2009}
}
@article{Mussel2010d,
author = {M{\"{u}}ssel, Christoph and Hopfensitz, Martin and Kestler, Hans},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/M{\"{u}}ssel, Hopfensitz, Kestler - 2010 - BoolNet package vignette.pdf:pdf},
journal = {Tutorial},
pages = {1--34},
title = {{BoolNet package vignette}},
year = {2010}
}
@article{Ostaszewski2018,
author = {Ostaszewski, Marek and Gebel, Stephan and Kuperstein, Inna and Mazein, Alexander and Zinovyev, Andrei and Dogrusoz, Ugur and Hasenauer, Jan and Fleming, Ronan M T and Gawron, Piotr and Ligon, Thomas and Niarakis, Anna and Nickerson, David and Weindl, Daniel and Balling, Rudi and Barillot, Emmanuel and Auffray, Charles and Schneider, Reinhard},
doi = {10.1093/bib/bby024},
file = {:Users/ozlem/Desktop/papers/bby024.pdf:pdf},
issn = {1467-5463},
journal = {Briefings In Bioinformatics},
number = {June},
pages = {1--12},
title = {{OUP accepted manuscript}},
url = {http://fdslive.oup.com/www.oup.com/pdf/production{\_}in{\_}progress.pdf},
year = {2018}
}
@article{Hin2004,
abstract = {A genetic interaction network containing?1000 genes and?4000 interactions was mapped by crossing mutations in 132 different query genes into a set of ?4700 viable gene yeast deletion mutants and scoring the double mutant progeny for fitness defects.Network connectivity was predictive of function because interactions often occurred among functionally related genes, and similar patterns of interactions tended to identify components of the same pathway.The genetic network exhibited dense local neighborhoods; therefore, the position of a gene on a partially mapped network is predictive of other genetic interactions.Because digenic interactions are common in yeast, similar networks may underlie the complex genetics associated with inherited phe- notypes in other organisms.},
author = {Hin, Amy and Tong, Yan and Lesage, Guillaume and Bader, Gary D and Ding, Huiming and Xu, Hong and Xin, Xiaofeng and Young, James and Berriz, Gabriel F and Brost, Renee L and Chang, Michael and Chen, Yiqun and Cheng, Xin and Chua, Gordon and Friesen, Helena and Goldberg, Debra S and Haynes, Jennifer and Humphries, Christine and He, Grace and Hussein, Shamiza and Ke, Lizhu and Krogan, Nevan and Li, Zhijian and Levinson, Joshua N and Lu, Hong and Me, Patrice and Munyana, Christella and Parsons, Ainslie B and Ryan, Owen and Tonikian, Raffi and Roberts, Tania and Sdicu, Anne-marie and Shapiro, Jesse and Sheikh, Bilal and Suter, Bernhard and Wong, Sharyl L and Zhang, Lan V and Zhu, Hongwei and Burd, Christopher G and Munro, Sean and Sander, Chris and Rine, Jasper and Greenblatt, Jack and Peter, Matthias and Bretscher, Anthony and Bell, Graham and Roth, Frederick P and Brown, Grant W and Andrews, Brenda and Bussey, Howard and Boone, Charles},
doi = {10.1126/science.1091317},
journal = {Science},
number = {5659},
pages = {808--814},
title = {{Global mapping of the yeast genetic interaction network}},
volume = {303},
year = {2004}
}
@article{Simon2009,
abstract = {The technological advances in DNA sequencing over the past five years have changed our approaches to gene expression analysis, fundamentally altering the basic methods used and in most cases driving a shift from hybridization-based approaches to sequencing-based approaches. Quantitative, tag-based studies of gene expression were one of the earliest applications of these next-generation technologies, but the tremendous depth of sequencing facilitates de novo transcript discovery, which replaces traditional expressed sequence tag (EST) sequencing. In addition, these technologies have created new opportunities for understanding the generation, stability, and decay of RNA and the impacts of chromatin differences on gene expression. As we review the impact of these methods on plant biology, we also mention published studies from animal systems when the methods are broadly applicable. We can anticipate that the published work over the past few years is a harbinger of much broader studies that are yet to be published and are sure to further advance our understanding of plant genomes in a field changing at a dizzying pace.},
author = {Simon, Stacey A. and Zhai, Jixian and Nandety, Raja Sekhar and McCormick, Kevin P. and Zeng, Jia and Mejia, Diego and Meyers, Blake C.},
doi = {10.1146/annurev.arplant.043008.092032},
isbn = {1545-2123 (Electronic)},
issn = {1543-5008},
journal = {Annual Review of Plant Biology},
number = {1},
pages = {305--333},
pmid = {19575585},
title = {{Short-Read Sequencing Technologies for Transcriptional Analyses}},
url = {http://www.annualreviews.org/doi/10.1146/annurev.arplant.043008.092032},
volume = {60},
year = {2009}
}
@article{Soltoff1996,
abstract = {Although epidermal growth factor (EGF) activates phosphoinositide (PI) 3-kinase activity in a number of types of cells or cell lines, in most cases that we have investigated the p85 regulatory subunit of PI 3-kinase does not appear to bind directly to the EGF receptor. Previously we demonstrated that EGF-dependent activation of PI 3-kinase activity in A431 cells is accompanied by the binding of p85 to ErbB3, an EGF receptor homologue. However, this mechanism did not explain the large activation of PI 3-kinase activity that was found in PC12 and A549 cells, which possess little or no ErbB3. Here we provide evidence that the p120cbl proto-oncoprotein is an intracellular adapter protein that associates with PI 3-kinase and thus is involved in the EGF-dependent activation of this enzyme in these two cell lines. Using an anti-p120cbl antibody, we immunoprecipitated the EGF receptor from PC12 cells and PI 3-kinase activity from PC12 and A549 cells in an EGF-dependent fashion. Treatment of PC12 cells with nerve growth factor or insulin stimulated large increases in PI 3-kinase activity that was immunoprecipitated using anti-Tyr(P) antibody but not using anti-p120cbl antibody. In EGF-treated PC12 cells, the tyrosine phosphorylation of p120cbl displayed similar kinetics to the activation of PI 3-kinase as measured by both in vivo lipid production and lipid kinase assays conducted using anti-p120cbl and anti-Tyr(P) immunoprecipitates. The use of glutathione S-transferase fusion proteins of various domains of p85 demonstrated that p120cbl associated with both the SH2 and SH3 domains of p85. p120cbl was also present in A431 cells and offers an additional pathway by which EGF can activate PI 3-kinase in these cells.},
author = {Soltoff, Stephen P. and Cantley, Lewis C.},
doi = {10.1074/jbc.271.1.563},
isbn = {0021-9258 (Print)},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {8550620},
title = {{p120cblis a cytosolic adapter protein that associates with phosphoinositide 3-kinase in response to epidermal growth factor in PC 12 and other cells}},
year = {1996}
}
@misc{Ashyraliyev2009,
abstract = {Mathematical models of biological processes have various applications: to assist in understanding the functioning of a system, to simulate experiments before actually performing them, to study situations that cannot be dealt with experimentally, etc. Some parameters in the model can be directly obtained from experiments or from the literature. Others have to be inferred by comparing model results to experiments. In this minireview, we discuss the identifiability of models, both intrinsic to the model and taking into account the available data. Furthermore, we give an overview of the most frequently used approaches to search the parameter space.},
author = {Ashyraliyev, Maksat and Fomekong-Nanfack, Yves and Kaandorp, Jaap A. and Blom, Joke G.},
booktitle = {FEBS Journal},
doi = {10.1111/j.1742-4658.2008.06844.x},
isbn = {1742-464X},
issn = {1742464X},
keywords = {A prioiri and a posteriori identifiability,Local and global optimization,Parameter estimation},
pmid = {19215296},
title = {{Systems biology: Parameter estimation for biochemical models}},
year = {2009}
}
@article{Kanshin2015,
abstract = {If specific and functional kinase- or phosphatase-substrate interactions are optimized for binding compared to promiscuous interactions, then changes in phosphorylation should occur faster on functional versus promiscuous substrates. To test this hypothesis, we designed a high temporal resolution global phosphoproteomics protocol to study the high-osmolarity glycerol (HOG) response in the budding yeast Saccharomyces cerevisiae. The method provides accurate, stimulus-specific measurement of phosphoproteome changes, quantitative analysis of phosphodynamics at sub-minute temporal resolution, and detection of more phosphosites. Rates of evolution of dynamic phosphosites were comparable to those of known functional phosphosites and significantly lower than static or longer-time-frame dynamic phosphosites. Kinetic profile analyses indicated that putatively functional kinase- or phosphatase-substrate interactions occur more rapidly, within 60 s, than promiscuous interactions. Finally, we report many changes in phosphorylation of proteins implicated in cytoskeletal and mitotic spindle dynamics that may underlie regulation of cell cycle and morphogenesis.},
author = {Kanshin, Evgeny and Bergeron-Sandoval, Louis Philippe and Isik, S. Sinan and Thibault, Pierre and Michnick, Stephen W.},
doi = {10.1016/j.celrep.2015.01.052},
isbn = {2211-1247 (Electronic)},
issn = {22111247},
journal = {Cell Reports},
number = {7},
pages = {1202--1214},
pmid = {25704821},
title = {{A Cell-Signaling Network Temporally Resolves Specific versus Promiscuous Phosphorylation}},
volume = {10},
year = {2015}
}
@article{Cyranoski2015,
abstract = {In wake of paper describing genetic modification of human embryos, scientists disagree about ethics.},
author = {Cyranoski, David and Reardon, Sara},
doi = {10.1038/520593a},
isbn = {1476-4687 (Electronic)$\backslash$r0028-0836 (Linking)},
issn = {0028-0836},
journal = {Nature},
number = {7549},
pages = {593--595},
pmid = {25925450},
title = {{Embryo editing sparks epic debate}},
url = {http://www.nature.com/doifinder/10.1038/520593a},
volume = {520},
year = {2015}
}
@article{Mojica2005,
abstract = {Prokaryotes contain short DN repeats known as CRISPR, recognizable by the regular spacing existing between the recurring units. They represent the most widely distributed family of repeats among prokaryotic genomes suggesting a biological function. The origin of the intervening sequences, at present unknown, could provide clues about their biological activities. Here we show that CRISPR spacers derive from preexisting sequences, either chromosomal or within transmissible genetic elements such as bacteriophages and conjugative plasmids. Remarkably, these extrachromosomal elements fail to infect the specific spacer-carrier strain, implying a relationship between CRISPR and immunity against targeted DNA. Bacteriophages and conjugative plasmids are involved in prokaryotic population control, evolution, and pathogenicity. All these biological traits could be influenced by the presence of specific spacers. CRISPR loci can be visualized as mosaics of a repeated unit, separated by sequences at some time present elsewhere in the cell.},
author = {Mojica, F. J M and D{\'{i}}ez-Villase{\~{n}}or, C{\'{e}}sar and Garc{\'{i}}a-Mart{\'{i}}nez, Jes{\'{u}}s and Soria, Elena},
doi = {10.1007/s00239-004-0046-3},
isbn = {0022-2844 (Print)$\backslash$r0022-2844 (Linking)},
issn = {00222844},
journal = {Journal of Molecular Evolution},
keywords = {Bacteriophages,CRISPR,Conjugative plasmids,DNA repeats,Lateral gene transfer,Pathogenicity,Prokaryotic evolution},
number = {2},
pages = {174--182},
pmid = {15791728},
title = {{Intervening sequences of regularly spaced prokaryotic repeats derive from foreign genetic elements}},
volume = {60},
year = {2005}
}
@article{Morishima2010,
abstract = {GABA plays an important role in inhibitory neurotransmission. In the developing brain, GABA also acts as a paracrine chemical mediator. To evaluate the ambient GABA gradients in the brain, an enzyme-linked imaging system that consisted of GABase and NADP+ was developed. In rat cerebellar slices, GABA release was observed in the layers containing GABAergic neurons. In telencephalic slices from embryonic GAD67-GFP knock-in mice, ambient GABA levels were high in the ganglionic eminence, where GABA cells are generated, but missing in homozygotes. This study indicates that this method will be useful to study the topography and dynamics of ambient GABA concentrations. ?? 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society.},
author = {Morishima, Toshitaka and Uematsu, Masakazu and Furukawa, Tomonori and Yanagawa, Yuchio and Fukuda, Atsuo and Yoshida, Sachiko},
doi = {10.1016/j.neures.2010.04.005},
issn = {01680102},
journal = {Neuroscience Research},
keywords = {Ambient GABA,Cerebellum,GABA,GAD,GAD67-GFP knock-in,Ganglionic eminence},
number = {4},
pages = {347--353},
pmid = {20399238},
title = {{GABA imaging in brain slices using immobilized enzyme-linked photoanalysis}},
volume = {67},
year = {2010}
}
@article{Shay2006,
abstract = {It has been approximately a decade since telomerase was described as an almost universal marker for human cancer. Most human tumours not only express telomerase but also have very short telomeres, whereas telomerase activity is either reduced or absent in normal tissues, making the inhibition of telomerase an attractive target for cancer therapeutics. Here we review the current status of telomerase therapeutics and discuss future opportunities and challenges for telomerase research, including a possible relationship with cancer stem cells that could be a source of chemo-/radioresistance development in many advanced cancers.s},
author = {Shay, Jerry W. and Wright, Woodring E.},
doi = {10.1038/nrd2081},
isbn = {1474-1776 (Print)},
issn = {1474-1776},
journal = {Nature Reviews Drug Discovery},
number = {7},
pages = {577--584},
pmid = {16773071},
title = {{Telomerase therapeutics for cancer: challenges and new directions}},
url = {http://www.nature.com/doifinder/10.1038/nrd2081},
volume = {5},
year = {2006}
}
@article{Cao1996,
abstract = {STAT proteins are a group of latent cytoplasmic transcription factors which function as signal transducers and activators of transcription. Stat1 and -2 were originally identified to function in interferon signaling, and Stat1 was also found to be activated by epidermal growth factor (EGF) and other cytokines. New members of the STAT gene family are identified. Among them, Stat3 has 52.5{\%} amino acid sequence homology with Stat1 and is activated by platelet-derived growth factor (PDGF), colony-stimulating factor 1 (CSF-1), EGF, interleukin-6, and other cytokines. Treatment of cells with EGF activates Stat1 and Stat3, which become phosphorylated on tyrosine residues to form homo - or heterodimers and translocate into the nucleus, binding to the sis-inducible element (SIE) in the c-fos promoter. Somatic cell genetic analyses demonstrated that Jaks, a family of nontransmembrane protein tyrosine kinases, are required for the activation of Stat1 and Stat2 in interferon-treated cells. However, little is known about the activation of Stat3 by growth factors. Here we report that in all v-Src-transformed cell lines examined, Stat3 is constitutively activated to bind to DNA and the phosphorylation of tyrosine on Stat3 is enhanced by the induction of v-Src expression. We also report that Src is shown to be associated with Stat3 in vivo, as well as in vitro, and phosphorylates Stat3 in vitro. Stat3 is also activated by CSF-1, possibly through CSF-1 receptor-c Src association in NIH 3T3 cells overexpressing CSF-1 receptors. Together, the data suggest that Src is involved in activation of Stat3 in growth factor signal transduction.},
author = {Cao, X and Tay, A and Guy, G R and Tan, Y H},
issn = {0270-7306},
journal = {Molecular and cellular biology},
month = {apr},
number = {4},
pages = {1595--1603},
title = {{Activation and association of Stat3 with Src in v-Src-transformed cell lines}},
url = {https://www.ncbi.nlm.nih.gov/pubmed/8657134 https://www.ncbi.nlm.nih.gov/pmc/PMC231145/},
volume = {16},
year = {1996}
}
@article{Kim2017,
abstract = {A detailed approach to the complex hopping transport in organic semiconductors is presented and used to describe experimental data from Maennig et al. [Phys. Rev. B 64, 195208 (2001)] on the effect of doping on conductivity, mobility and thermopower. In this approach, the energetic distribution of the charge carriers in a Gaussian shaped density of states (DOS) is calculated under thermal equilibrium conditions and compared to the energetic distribution of the current. The description is based on the Miller–Abraham model for hopping in a disordered material and utilizes the so-called transport energy concept. To include also the case of higher electron concentrations in the tail states of the DOS the Fermi distribution was taken into account. Furthermore, additional trap states in the gap are considered to describe the experimental data at low doping concentration more correctly. In the framework of the model there is no indication of a thermally activated ionization of the dopants. In contrast to other descriptions, the position of the Fermi energy and transport energy are calculated from the model. It is demonstrated that the principal behavior of the transport parameter can be well explained in terms of classical semiconductor physics.},
author = {Kim, In Su and Koppula, Sushruta and Park, Shin Young and Choi, Dong Kug},
doi = {10.3390/ijms18020430},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/ijms-18-00430.pdf:pdf},
isbn = {0021-8979},
issn = {14220067},
journal = {International Journal of Molecular Sciences},
keywords = {1-methyl-4-phenylpyridinium,EGFR,Microarray analysis,Parkinson's disease,SH-SY5Y cells},
number = {2},
pages = {1--15},
title = {{Analysis of epidermal growth factor receptor related gene expression changes in a cellular and animal model of Parkinson's disease}},
volume = {18},
year = {2017}
}
@article{Tanabe2012,
abstract = {KEGG (Kyoto Encyclopedia of Genes and Genomes) is a bioinformatics resource for understanding the functions and utilities of cells and organisms from both high-level and genomic perspectives. It is a self-sufficient, integrated resource consisting of genomic, chemical, and network information, with cross-references to numerous outside databases, containing a complete set of building blocks (genes and molecules) and wiring diagrams (interaction networks) to represent cellular functions. This unit describes protocols for using KEGG, KEGG PATHWAY, KEGG GENES, KEGG SSDB, KEGG EXPRESSION, and KEGG LIGAND. Protocols are also described for how to color maps, compare chemical compounds and glycan chains, analyze Ortholog Clusters, and visualize and analyze microarray data, among other procedures. All of these many protocols enable the user to take advantage of the full breadth of the functionality provided by KEGG.},
author = {Tanabe, Mao and Kanehisa, Minoru},
doi = {10.1002/0471250953.bi0112s38},
isbn = {0471250953},
issn = {19343396},
journal = {Current Protocols in Bioinformatics},
keywords = {BRITE functional hierarchy,Chemical information analysis,Genome annotation,KEGG pathway map,Molecular network},
pmid = {18428742},
title = {{Using the KEGG database resource}},
year = {2012}
}
@article{Saez-Rodriguez2008a,
abstract = {MOTIVATION Linking experimental data to mathematical models in biology is impeded by the lack of suitable software to manage and transform data. Model calibration would be facilitated and models would increase in value were it possible to preserve links to training data along with a record of all normalization, scaling, and fusion routines used to assemble the training data from primary results. RESULTS We describe the implementation of DataRail, an open source MATLAB-based toolbox that stores experimental data in flexible multi-dimensional arrays, transforms arrays so as to maximize information content, and then constructs models using internal or external tools. Data integrity is maintained via a containment hierarchy for arrays, imposition of a metadata standard based on a newly proposed MIDAS format, assignment of semantically typed universal identifiers, and implementation of a procedure for storing the history of all transformations with the array. We illustrate the utility of DataRail by processing a newly collected set of approximately 22 000 measurements of protein activities obtained from cytokine-stimulated primary and transformed human liver cells. AVAILABILITY DataRail is distributed under the GNU General Public License and available at http://code.google.com/p/sbpipeline/},
author = {Saez-Rodriguez, Julio and Goldsipe, Arthur and Muhlich, Jeremy and Alexopoulos, Leonidas G. and Millard, Bjorn and Lauffenburger, Douglas A. and Sorger, Peter K.},
doi = {10.1093/bioinformatics/btn018},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Saez-Rodriguez et al. - 2008 - Flexible informatics for linking experimental data to mathematical models via DataRail.pdf:pdf},
isbn = {1460-2059 (Electronic)},
issn = {13674803},
journal = {Bioinformatics},
pmid = {18218655},
title = {{Flexible informatics for linking experimental data to mathematical models via DataRail}},
year = {2008}
}
@article{Dunkel2006,
abstract = {Although tremendous effort has been put into synthetic libraries, most drugs on the market are still natural compounds or derivatives thereof. There are encyclopaedias of natural compounds, but the availability of these compounds is often unclear and catalogues from numerous suppliers have to be checked. To overcome these problems we have compiled a database of approximately 50,000 natural compounds from different suppliers. To enable efficient identification of the desired compounds, we have implemented substructure searches with typical templates. Starting points for in silico screenings are about 2500 well-known and classified natural compounds from a compendium that we have added. Possible medical applications can be ascertained via automatic searches for similar drugs in a free conformational drug database containing WHO indications. Furthermore, we have computed about three million conformers, which are deployed to account for the flexibilities of the compounds when the 3D superposition algorithm that we have developed is used. The SuperNatural Database is publicly available at http://bioinformatics.charite.de/supernatural. Viewing requires the free Chime-plugin from MDL (Chime) or Java2 Runtime Environment (MView), which is also necessary for using Marvin application for chemical drawing.},
author = {Dunkel, M.},
doi = {10.1093/nar/gkj132},
isbn = {1362-4962 (Electronic)$\backslash$r0305-1048 (Linking)},
issn = {0305-1048},
journal = {Nucleic Acids Research},
number = {90001},
pages = {D678--D683},
pmid = {16381957},
title = {{SuperNatural: a searchable database of available natural compounds}},
url = {https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkj132},
volume = {34},
year = {2006}
}
@article{Whitman1988,
abstract = {The generation of second messengers from the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdInsP2) by phosphoinositidase C has been implicated in the mediation of cellular responses to a variety of growth factors and oncogene products. The first step in the production of PtdInsP2 from phosphatidylinositol (PtdIns) is catalysed by PtdIns kinase. A PtdIns kinase activity has been found to associate specifically with several oncogene products, as well as with the platelet-derived growth factor (PDGF) receptor. We have previously identified two biochemically distinct PtdIns kinases in fibroblasts, and have found that only one of these, designated type I, specifically associates with activated tyrosine kinases. We have now characterized the site on the inositol ring phosphorylated by type I PtdIns kinase, and find that this kinase specifically phosphorylates the D-3 ring position to generate a novel phospholipid, phosphatidylinositol-3-phosphate (PtdIns(3)P). In contrast, the main PtdIns kinase in fibroblasts, designated type II, specifically phosphorylates the D-4 position to produce phosphatidylinositol-4-phosphate (PtdIns(4)P), previously considered to be the only form of PtdInsP. We have also tentatively identified PtdIns(3)P as a minor component of total PtdInsP in intact fibroblasts. We propose that type I PtdIns kinase is responsible for the generation of PtdIns(3)P in intact cells, and that this novel phosphoinositide could be important in the transduction of mitogenic and oncogenic signals.},
author = {Whitman, Malcolm and Downes, C. Peter and Keeler, Marilyn and Keller, Tracy and Cantley, Lewis},
doi = {10.1038/332644a0},
isbn = {0028-0836 (Print)$\backslash$n0028-0836 (Linking)},
issn = {00280836},
journal = {Nature},
pmid = {2833705},
title = {{Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate}},
year = {1988}
}
@article{Bewley1998,
abstract = {The solution structure of cyanovirin-N, a potent 11,000 Mr HIV-inactivating protein that binds with high affinity and specificity to the HIV surface envelope protein gp120, has been solved by nuclear magnetic resonance spectroscopy, including extensive use of dipolar couplings which provide a priori long range structural information. Cyanovirin-N is an elongated, largely beta-sheet protein that displays internal two-fold pseudosymmetry. The two sequence repeats (residues 1-50 and 51-101) share 32{\%} sequence identity and superimpose with a backbone atomic root-mean-square difference of 1.3 A. The two repeats, however, do not form separate domains since the overall fold is dependent on numerous contacts between them. Rather, two symmetrically related domains are formed by strand exchange between the two repeats. Analysis of surface hydrophobic clusters suggests the location of potential binding sites for protein-protein interactions.},
author = {Bewley, C a and Gustafson, K R and Boyd, M R and Covell, D G and Bax, a and Clore, G M and Gronenborn, a M},
doi = {10.1038/828},
isbn = {1072-8368 (Print)},
issn = {1072-8368},
journal = {Nature structural biology},
keywords = {Amino Acid Sequence,Anti-HIV Agents,Anti-HIV Agents: chemistry,Bacterial Proteins,Binding Sites,Carrier Proteins,Carrier Proteins: chemistry,Crystallography, X-Ray,Models, Molecular,Molecular Sequence Data,Nuclear Magnetic Resonance, Biomolecular,Protein Structure, Secondary,Protein Structure, Tertiary,Sequence Alignment},
number = {7},
pages = {571--8},
pmid = {9665171},
title = {{Solution structure of cyanovirin-N, a potent HIV-inactivating protein.}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/12473463},
volume = {5},
year = {1998}
}
@misc{Klebe2006,
abstract = {In contrast to high-throughput screening, in virtual ligand screening (VS), compounds are selected using computer programs to predict their binding to a target receptor. A key prerequisite is knowledge about the spatial and energetic criteria responsible for protein-ligand binding. The concepts and prerequisites to perform VS are summarized here, and explanations are sought for the enduring limitations of the technology. Target selection, analysis and preparation are discussed, as well as considerations about the compilation of candidate ligand libraries. The tools and strategies of a VS campaign, and the accuracy of scoring and ranking of the results, are also considered. ?? 2006 Elsevier Ltd. All rights reserved.},
author = {Klebe, Gerhard},
booktitle = {Drug Discovery Today},
doi = {10.1016/j.drudis.2006.05.012},
isbn = {1359-6446},
issn = {13596446},
number = {13-14},
pages = {580--594},
pmid = {16793526},
title = {{Virtual ligand screening: strategies, perspectives and limitations}},
volume = {11},
year = {2006}
}
@inproceedings{Macdonald1996,
abstract = {Huntington's disease (HD) is a dominant neurodegenerative disorder caused by expansion of a CAG repeat in the gene encoding huntingtin, a protein of unknown function. To distinguish between "loss of function" and "gain of function" models of HD, the murine HD homolog Hdh was inactivated by gene targeting. Mice heterozygous for Hdh inactivation were phenotypically normal, whereas homozygosity resulted in embryonic death. Homozygotes displayed abnormal gastrulation at embryonic day 7.5 and were resorbing by day 8.5. Thus, huntingtin is critical early in embryonic development, before the emergence of the nervous system. That Hdh inactivation does not mimic adult HD neuropathology suggests that the human disease involves a gain of function.},
author = {Macdonald, M. E. and Duyao, M. and Calzonetti, T. and Auerbach, A. and Ryan, A. and Barnes, G. and White, J. K. and Auerbach, W. and Vonsattel, J. P. and Gusella, J. F. and Joyner, A. L.},
booktitle = {Cold Spring Harbor Symposia on Quantitative Biology},
doi = {10.1126/science.7618107},
isbn = {0036-8075},
issn = {00917451},
pages = {627--638},
pmid = {7618107},
title = {{Targeted inactivation of the mouse Huntington's disease gene homolog Hdh}},
volume = {61},
year = {1996}
}
@article{Saez-Rodriguez2009,
abstract = {Large-scale protein signalling networks are useful for exploring complex biochemical pathways but do not reveal how pathways respond to specific stimuli. Such specificity is critical for understanding disease and designing drugs. Here we describe a computational approach--implemented in the free CNO software--for turning signalling networks into logical models and calibrating the models against experimental data. When a literature-derived network of 82 proteins covering the immediate-early responses of human cells to seven cytokines was modelled, we found that training against experimental data dramatically increased predictive power, despite the crudeness of Boolean approximations, while significantly reducing the number of interactions. Thus, many interactions in literature-derived networks do not appear to be functional in the liver cells from which we collected our data. At the same time, CNO identified several new interactions that improved the match of model to data. Although missing from the starting network, these interactions have literature support. Our approach, therefore, represents a means to generate predictive, cell-type-specific models of mammalian signalling from generic protein signalling networks.},
author = {Saez-Rodriguez, Julio and Alexopoulos, Leonidas G. and Epperlein, Jonathan and Samaga, Regina and Lauffenburger, Douglas A. and Klamt, Steffen and Sorger, Peter K.},
doi = {10.1038/msb.2009.87},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Saez-Rodriguez et al. - 2009 - Discrete logic modelling as a means to link protein signalling networks with functional analysis of mamma.pdf:pdf},
isbn = {1744-4292},
issn = {17444292},
journal = {Molecular Systems Biology},
keywords = {Logical modelling,Protein networks,Signal transduction},
number = {331},
pages = {1--19},
pmid = {19953085},
publisher = {Nature Publishing Group},
title = {{Discrete logic modelling as a means to link protein signalling networks with functional analysis of mammalian signal transduction}},
url = {http://dx.doi.org/10.1038/msb.2009.87},
volume = {5},
year = {2009}
}
@article{Feng2004,
abstract = {The tumor suppressor p53 is commonly inhibited under conditions in which the phosphatidylinositide 3'-OH kinase/protein kinase B (PKB)Akt pathway is activated. Intracellular levels of p53 are controlled by the E3 ubiquitin ligase Mdm2. Here we show that PKB inhibits Mdm2 self-ubiquitination via phosphorylation of Mdm2 on Ser(166) and Ser(188). Stimulation of human embryonic kidney 293 cells with insulin-like growth factor-1 increased Mdm2 phosphorylation on Ser(166) and Ser(188) in a phosphatidylinositide 3'-OH kinase-dependent manner, and the treatment of both human embryonic kidney 293 and COS-1 cells with phosphatidylinositide 3'-OH kinase inhibitor LY-294002 led to proteasome-mediated Mdm2 degradation. Introduction of a constitutively active form of PKB together with Mdm2 into cells induced phosphorylation of Mdm2 at Ser(166) and Ser(188) and stabilized Mdm2 protein. Moreover, mouse embryonic fibroblasts lacking PKBalpha displayed reduced Mdm2 protein levels with a concomitant increase of p53 and p21(Cip1), resulting in strongly elevated apoptosis after UV irradiation. In addition, activation of PKB correlated with Mdm2 phosphorylation and stability in a variety of human tumor cells. These findings suggest that PKB plays a critical role in controlling of the Mdm2.p53 signaling pathway by regulating Mdm2 stability.},
author = {Feng, J and Tamaskovic, R and Yang, Z and Brazil, D P and Merlo, A and Hess, D and Hemmings, B A},
doi = {10.1074/jbc.M404936200},
isbn = {0021-9258 (Print)$\backslash$n0021-9258 (Linking)},
issn = {0021-9258},
journal = {J Biol Chem},
keywords = {Animals,Cell Line,Enzyme Stability,Humans,Mice,Mice, Knockout,Nuclear Proteins/chemistry/*metabolism,Phosphatidylinositol 3-Kinases/metabolism,Phosphorylation,Proteasome Endopeptidase Complex/metabolism,Protein-Serine-Threonine Kinases/*metabolism,Proto-Oncogene Proteins c-akt,Proto-Oncogene Proteins c-mdm2,Proto-Oncogene Proteins/chemistry/*metabolism,Signal Transduction,Tumor Suppressor Protein p53/metabolism,Ubiquitins},
pmid = {15169778},
title = {{Stabilization of Mdm2 via decreased ubiquitination is mediated by protein kinase B/Akt-dependent phosphorylation}},
year = {2004}
}
@article{Didychuk2016,
abstract = {Base-pairing of U4 and U6 snRNAs during di-snRNP assembly requires large-scale remodeling of RNA structure that is chaperoned by the U6 snRNP protein Prp24. We investigated the mechanism of U4/U6 annealing in vitro using an assay that enables visualization of ribonucleoprotein complexes and faithfully recapitulates known in vivo determinants for the process. We find that annealing, but not U6 RNA binding, is highly dependent on the electropositive character of a 20 A-wide groove on the surface of Prp24. During annealing, we observe the formation of a stable ternary complex between U4 and U6 RNAs and Prp24, indicating that displacement of Prp24 in vivo requires additional factors. Mutations that stabilize the U6 'telestem' helix increase annealing rates by up to 15-fold, suggesting that telestem formation is rate-limiting for U4/U6 pairing. The Lsm2-8 complex, which binds adjacent to the telestem at the 3' end of U6, provides a comparable rate enhancement. Collectively, these data identify domains of the U6 snRNP that are critical for one of the first steps in assembly of the megaDalton U4/U6.U5 tri-snRNP complex, and lead to a dynamic model for U4/U6 pairing that involves a striking degree of evolved cooperativity between protein and RNA.},
author = {Didychuk, Allison L. and Montemayor, Eric J. and Brow, David A. and Butcher, Samuel E.},
doi = {10.1093/nar/gkv1374},
issn = {13624962},
journal = {Nucleic Acids Research},
number = {3},
pages = {1398--1410},
pmid = {26673715},
title = {{Structural requirements for protein-catalyzed annealing of U4 and U6 RNAs during di-snRNP assembly}},
volume = {44},
year = {2016}
}
@article{Siegle2018,
abstract = {Aging is a complex biological process, which determines the life span of an organism. Insulin-like growth factor (IGF) and Wnt signaling pathways govern the process of aging. Both pathways share common downstream targets that allow competitive crosstalk between these branches. Of note, a shift from IGF to Wnt signaling has been observed during aging of satellite cells. Biological regulatory networks necessary to recreate aging have not yet been discovered. Here, we established a mathematical in silico model that robustly recapitulates the crosstalk between IGF and Wnt signaling. Strikingly, it predicts critical nodes following a shift from IGF to Wnt signaling. These findings indicate that this shift might cause age-related diseases.},
author = {Siegle, Lea and Schwab, Julian D. and K{\"{u}}hlwein, Silke D. and Lausser, Ludwig and T{\"{u}}mpel, Stefan and Pfister, Astrid S. and K{\"{u}}hl, Michael and Kestler, Hans A.},
doi = {10.1371/journal.pone.0195126},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Siegle et al. - 2018 - A Boolean network of the crosstalk between IGF and Wnt signaling in aging satellite cells.pdf:pdf},
isbn = {1111111111},
issn = {19326203},
journal = {PLoS ONE},
number = {3},
pages = {1--24},
pmid = {29596489},
title = {{A Boolean network of the crosstalk between IGF and Wnt signaling in aging satellite cells}},
volume = {13},
year = {2018}
}
@article{Lepingle2000,
abstract = {By analyzing 2830 random sequence tags (RSTs), totalling 2.7 Mb, we explored the genome of the marine, osmo- and halotolerant yeast, Debaryomyces hansenii. A contig 29 kb in length harbors the entire mitochondrial genome. The genes encoding Cox1, Cox2, Cox3, Cob, Atp6, Atp8, Atp9, several subunits of the NADH dehydrogenase complex 1 and 11 tRNAs were unambiguously identified. An equivalent number of putative transposable elements compared to Saccharomyces cerevisiae were detected, the majority of which are more related to higher eukaryote copia elements. BLASTX comparisons of RSTs with databases revealed at least 1119 putative open reading frames with homology to S. cerevisiae and 49 to other genomes. Specific functions, including transport of metabolites, are clearly over-represented in D. hansenii compared to S. cerevisiae, consistent with the observed difference in physiology of the two species. The sequences have been deposited with EMBL under the accession numbers AL436045-AL438874. ?? 2000 Federation of European Biochemical Societies.},
author = {L{\'{e}}pingle, Andr{\'{e}}e and Casaregola, Serge and Neuv{\'{e}}glise, C{\'{e}}cile and Bon, Elisabeth and Nguyen, Huu Vang and Artiguenave, Fran{\c{c}}ois and Wincker, Patrick and Gaillardin, Claude},
doi = {10.1016/S0014-5793(00)02285-7},
isbn = {0014-5793},
issn = {00145793},
journal = {FEBS Letters},
keywords = {Mitochondrial DNA,Non-conventional yeast,Retrotransposon,Ribosomal DNA},
number = {1},
pages = {82--86},
pmid = {11152889},
title = {{Genomic exploration of the hemiascomycetous yeasts: 14. Debaryomyces hansenii var. hansenii}},
volume = {487},
year = {2000}
}
@article{Didier2011,
abstract = {This paper deals with the generalized logical framework defined by Ren{\'{e}} Thomas in the 70's to qualitatively represent the dynamics of regulatory networks. In this formalism, a regulatory network is represented as a graph, where nodes denote regulatory components (basically genes) and edges denote regulations between these components. Discrete variables are associated to regulatory components accounting for their levels of expression. In most cases, Boolean variables are enough, but some situations may require further values. Despite this fact, the majority of tools dedicated to the analysis of logical models are restricted to the Boolean case. A formal Boolean mapping of multivalued logical models is a natural way of extending the applicability of these tools.Three decades ago, a multivalued to Boolean variable mapping was proposed by P. Van Ham. Since then, all works related to multivalued logical models and using a Boolean representation rely on this particular mapping. We formally show in this paper that this mapping is actually the sole, up to cosmetic changes, that could preserve the regulatory structures of the underlying graphs as well as their dynamical behaviours. {\textcopyright} 2010 Elsevier Ltd.},
author = {Didier, Gilles and Remy, Elisabeth and Chaouiya, Claudine},
doi = {10.1016/j.jtbi.2010.09.017},
isbn = {0022-5193},
issn = {00225193},
journal = {Journal of Theoretical Biology},
keywords = {Boolean modelling,Cell dynamics,Gene Regulatory Networks,Multivalued modelling},
pmid = {20868697},
title = {{Mapping multivalued onto Boolean dynamics}},
year = {2011}
}
@article{Smith2011,
abstract = {What gives an organism the ability to regrow tissues and to recover function where another organism fails is the central problem of regenerative biology. The challenge is to describe the mechanisms of regeneration at the molecular level, delivering detailed insights into the many components that are cross-regulated. In other words, a broad, yet deep dissection of the system-wide network of molecular interactions is needed. Functional genomics has been used to elucidate gene regulatory networks (GRNs) in developing tissues, which, like regeneration, are complex systems. Therefore, we reason that the GRN approach, aided by next generation technologies, can also be applied to study the molecular mechanisms underlying the complex functions of regeneration. We ask what characteristics a model system must have to support a GRN analysis. Our discussion focuses on regeneration in the central nervous system, where loss of function has particularly devastating consequences for an organism. We examine a cohort of cells conserved across all vertebrates, the reticulospinal (RS) neurons, which lend themselves well to experimental manipulations. In the lamprey, a jawless vertebrate, there are giant RS neurons whose large size and ability to regenerate make them particularly suited for a GRN analysis. Adding to their value, a distinct subset of lamprey RS neurons reproducibly fail to regenerate, presenting an opportunity for side-by-side comparison of gene networks that promote or inhibit regeneration. Thus, determining the GRN for regeneration in RS neurons will provide a mechanistic understanding of the fundamental cues that lead to success or failure to regenerate.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Smith, Joel and Morgan, Jennifer R. and Zottoli, Steven J. and Smith, Peter J. and Buxbaum, Joseph D. and Bloom, Ona E.},
doi = {10.1086/BBLv221n1p18},
eprint = {NIHMS150003},
file = {:Users/ozlem/Dropbox/papers/Biological Networks/BBLv221n1p18.pdf:pdf},
isbn = {0006-3185},
issn = {00063185},
journal = {Biological Bulletin},
pmid = {21876108},
title = {{Regeneration in the era of functional genomics and gene network analysis}},
year = {2011}
}
@article{Sander2014,
abstract = {Targeted genome editing using engineered nucleases has rapidly gone from being a niche technology to a mainstream method used by many biological researchers. This widespread adoption has been largely fueled by the emergence of the clustered, regularly interspaced, short palindromic repeat (CRISPR) technology, an important new approach for generating RNA-guided nucleases, such as Cas9, with customizable specificities. Genome editing mediated by these nucleases has been used to rapidly, easily and efficiently modify endogenous genes in a wide variety of biomedically important cell types and in organisms that have traditionally been challenging to manipulate genetically. Furthermore, a modified version of the CRISPR-Cas9 system has been developed to recruit heterologous domains that can regulate endogenous gene expression or label specific genomic loci in living cells. Although the genome-wide specificities of CRISPR-Cas9 systems remain to be fully defined, the power of these systems to perform targeted, highly efficient alterations of genome sequence and gene expression will undoubtedly transform biological research and spur the development of novel molecular therapeutics for human disease.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Sander, Jeffry D and Joung, J Keith},
doi = {10.1038/nbt.2842},
eprint = {NIHMS150003},
isbn = {1546-1696 (Electronic)$\backslash$n1087-0156 (Linking)},
issn = {1087-0156},
journal = {Nature Biotechnology},
number = {4},
pages = {347--355},
pmid = {24584096},
title = {{CRISPR-Cas systems for editing, regulating and targeting genomes}},
url = {http://www.nature.com/doifinder/10.1038/nbt.2842},
volume = {32},
year = {2014}
}
@article{Wang2015,
abstract = {The clustered regularly interspaced short palindromic repeat (CRISPR) gene editing technique, based on the non-homologous end-joining (NHEJ) repair pathway, has been used to generate gene knock-outs with variable sizes of small insertion/deletions with high efficiency. More precise genome editing, either the insertion or deletion of a desired fragment, can be done by combining the homology-directed-repair (HDR) pathway with CRISPR cleavage. However, HDR-mediated gene knock-in experiments are typically inefficient, and there have been no reports of successful gene knock-in with DNA fragments larger than 4 kb. Here, we describe the targeted insertion of large DNA fragments (7.4 and 5.8 kb) into the genomes of mouse embryonic stem (ES) cells and zygotes, respectively, using the CRISPR/HDR technique without NHEJ inhibitors. Our data show that CRISPR/HDR without NHEJ inhibitors can result in highly efficient gene knock-in, equivalent to CRISPR/HDR with NHEJ inhibitors. Although NHEJ is the dominant repair pathway associated with CRISPR-mediated double-strand breaks (DSBs), and biallelic gene knock-ins are common, NHEJ and biallelic gene knock-ins were not detected. Our results demonstrate that efficient targeted insertion of large DNA fragments without NHEJ inhibitors is possible, a result that should stimulate interest in understanding the mechanisms of high efficiency CRISPR targeting in general.},
archivePrefix = {arXiv},
arxivId = {arXiv:1011.1669v3},
author = {Wang, Bangmei and Li, Kunyu and Wang, Amy and Reiser, Michelle and Saunders, Thom and Lockey, Richard F. and Wang, Jia Wang},
doi = {10.2144/000114339},
eprint = {arXiv:1011.1669v3},
isbn = {0736-6205},
issn = {19409818},
journal = {BioTechniques},
keywords = {CRISPR cleavage,Double-strand break (DSB),Embryonic stem (ES) cells,Homology-directed-repair (HDR),Zygote},
number = {4},
pages = {201--208},
pmid = {26458548},
title = {{Highly efficient CRISPR/HDR-mediated knock-in for mouse embryonic stem cells and zygotes}},
volume = {59},
year = {2015}
}
@article{Hochachka2002,
abstract = {The study of biochemical adaption provides fascinating insights into how organisms "work" and how they evolve to sustain physiological function under a vast array of environmental conditions. This book describes how the abilities of organisms to thrive in widely different environments derive from two fundamental classes of biochemical adaptions: modifications of core biochemical processes that allow a common set of physiological functions to be conserved, and "inventions" of new biochemical traits that allow entry into novel habitats. Biochemical Adaptation: Mechanisms and Process in Physiological Evolution asks two primary questions. First, how have the core biochemical systems found in all species been adaptively modified to allow the same fundamental types of physiological processes to be sustained throughout the wide range of habitat conditions found in the biosphere? Second, through what types of genetic and biochemical processes have new physiological functions been fabricated? The primary audience for this book is faculty, senior undergraduates, and graduate students in environmental biology, comparative physiology, and marine biology. Other likely readers include workers in governmental laboratories concerned with environmental issues, medical students interested in some elements of the book, and medical researchers.},
author = {Hochachka, Pw Peter W and Somero, George N and Vi{\~{n}}a, Jos{\'{e}}},
doi = {10.1002/bmb.2002.494030030071},
isbn = {9780195117035},
issn = {00368075},
journal = {Biochemistry and Molecular Biology Education},
number = {3},
pages = {215--216},
pmid = {12383070},
title = {{Biochemical adaptation: Mechanism and process in physiological evolution}},
url = {http://doi.wiley.com/10.1002/bmb.2002.494030030071{\%}5Cnhttp://books.google.fr/books?id=gNkL{\_}un9644C{\&}printsec=frontcover{\&}dq=isbn:9780195117035{\&}hl={\&}cd=1{\&}source=gbs{\_}api{\%}5Cnpapers2://publication/uuid/4ABFBD43-1D4D-48C3-BF0B-35F9205557D3{\%}5Cnhttp://www.lavoisier},
volume = {30},
year = {2002}
}
@article{Caldu-Primo2017,
abstract = {Network biology aims to understand cell behavior through the analysis of underlying complex biomolecular networks. Inference of condition-specific interaction networks from epigenomic data enables the characterization of the structural plasticity that regulatory networks can acquire in different tissues of the same organism. From this perspective, uncovering specific patterns of variation by comparing network structure among tissues could provide insights into systems-level mechanisms underlying cell behavior. Following this idea, here we propose an empirical framework to analyze mammalian tissue-specific networks, focusing on characterizing and contrasting their structure and behavior in response to perturbations. We structurally represent the state of the cell/tissue by condition specific transcription factor networks generated using chromatin accessibility data, and we profile their systems behavior in terms of the structural robustness against random and directed perturbations. Using this framework, we unveil the structural heterogeneity existing among tissues at different levels of differentiation. We uncover a novel and conserved systems property of regulatory networks underlying embryonic stem cells (ESCs): in contrast to terminally differentiated tissues, the promiscuous regulatory connectivity of ESCs produces a globally homogeneous network resulting in increased structural robustness. Possible biological consequences of this property are discussed.},
author = {Caldu-Primo, Jose Luis and Alvarez-Buylla, Elena and Davila-Velderrain, Jose},
doi = {10.1101/209528},
file = {:Users/ozlem/Dropbox/papers/Biological Networks/s41598-018-32020-1.pdf:pdf},
issn = {2045-2322},
journal = {bioRxiv},
number = {November 2017},
pages = {209528},
title = {{Structural robustness of mammalian transcription factor networks reveals plasticity across development}},
url = {https://www.biorxiv.org/content/early/2017/10/27/209528},
year = {2017}
}
@article{D.2011,
abstract = {Systems Biology has taken advantage of computational tools and high-throughput experimental data to model several biological processes. These include signaling, gene regulatory, and metabolic networks. However, most of these models are specific to each kind of network. Their interconnection demands a whole-cell modeling framework for a complete understanding of cellular systems. We describe the features required by an integrated framework for modeling, analyzing and simulating biological processes, and review several modeling formalisms that have been used in Systems Biology including Boolean networks, Bayesian networks, Petri nets, process algebras, constraint-based models, differential equations, rule-based models, interacting state machines, cellular automata, and agent-based models. We compare the features provided by different formalisms, and discuss recent approaches in the integration of these formalisms, as well as possible directions for the future. {\textcopyright} 2011 Machado et al; licensee Springer.},
author = {D., Machado and R.S., Costa and M., Rocha and E.C., Ferreira and B., Tidor and I., Rocha},
doi = {10.1186/2191-0855-1-45},
isbn = {978-1-4614-4008-6},
issn = {2191-0855},
journal = {AMB Express},
keywords = {Biological networks,Modeling formalisms,Systems biology},
pmid = {22141422},
title = {{Modeling formalisms in systems biology}},
year = {2011}
}
@article{N.2009,
abstract = {The pathophysiology of depression has been assigned to the noradrenalin and serotonin system. Results of different studies also support a role of the dopaminergic system in depression: In particular, psychomotor retarded depressive patients exhibited lower levels of homovanillic acid (metabolite of dopamine). While the moodimproving effect of methylphenidat, D-amphetamin and cocaine is also supportive for an involvement of the dopaminergic system, reserpine leads to diminished dopamine levels and may induce a depressive syndrome as well as dopamine receptor-blockers. Dopamine-mediated motor disturbances and accompanying changes in mood in Parkinson's disease likewise support pathophysiological similarities pathophysiological similarities of depression and Parkinson's disease. Psychomotor inhibition, reduced facial expression and decreased speech production in depression are in line with a hypodopaminergic state of the respective motor areas. There is evidence from open studies for the ergotalkaloids bromocriptine and pergolide to have anti-depressive effects. Controlled studies for the selective dopamine D2/D3-agonists pramipexole and ropinirole are existing. Bupropion, a selective dopamine and noradrenaline reuptake inhibitor (DNRI), has proven antidepressant efficacy in controlled studies and has been licensed for the treatment of depression. {\textcopyright} 2009 Dustri-Verlag Dr. Karl Feistle.},
author = {N., Clausius and C., Born and H., Grunze},
issn = {0948-6259},
journal = {Neuropsychiatrie},
keywords = {Parkinson disease,amfebutamone,anorexia,bromocriptine,cabergoline,citalopram,clinical trial,cocaine,constipation,depression,dexamphetamine,diarrhea,dihydroergocryptine,dopamine receptor stimulating agent,dopaminergic system,drug efficacy,escitalopram,facial expression,fluoxetine,homovanillic acid,human,levodopa,lisuride,methylphenidate,motor dysfunction,nigroneostriatal system,noradrenalin uptake inhibitor,paroxetine,pathophysiology,pergolide,placebo,pramipexole,psychomotor performance,reserpine,review,ropinirole,serotoninergic system,sertraline,somnolence,speech,venlafaxine,wellbutrin,zyban},
number = {1},
pages = {15--25},
title = {{The relevance of dopamine agonists in the treatment of depression}},
url = {http://www.embase.com/search/results?subaction=viewrecord{\&}from=export{\&}id=L354699230{\%}5Cnhttp://www.dustri.com/nc/de/deutschsprachige-zeitschriften/mag/neuropsychiatrie.html{\%}5Cnhttp://sfx.library.uu.nl/utrecht?sid=EMBASE{\&}issn=09486259{\&}id=doi:{\&}atitle=The+rel},
volume = {23},
year = {2009}
}
@article{Wiedenheft2012,
abstract = {Clustered regularly interspaced short palindromic repeat (CRISPR) are essential components of nucleic-acid-based adaptive immune systems that are widespread in bacteria and archaea. Similar to RNA interference (RNAi) pathways in eukaryotes, CRISPR-mediated immune systems rely on small RNAs for sequence-specific detection and silencing of foreign nucleic acids, including viruses and plasmids. However, the mechanism of RNA-based bacterial immunity is distinct from RNAi. Understanding how small RNAs are used to find and destroy foreign nucleic acids will provide new insights into the diverse mechanisms of RNA-controlled genetic silencing systems.},
archivePrefix = {arXiv},
arxivId = {37},
author = {Wiedenheft, Blake and Sternberg, Samuel H. and Doudna, Jennifer A.},
doi = {10.1038/nature10886},
eprint = {37},
isbn = {1476-4687 (Electronic)$\backslash$n0028-0836 (Linking)},
issn = {0028-0836},
journal = {Nature},
number = {7385},
pages = {331--338},
pmid = {22337052},
title = {{RNA-guided genetic silencing systems in bacteria and archaea}},
url = {http://www.nature.com/doifinder/10.1038/nature10886},
volume = {482},
year = {2012}
}
@article{Carriere2011,
abstract = {The Ras/mitogen-activated protein kinase (MAPK) pathway regulates a variety of cellular processes by activating specific transcriptional and translational programs. Ras/MAPK signaling promotes mRNA translation and protein synthesis, but the exact molecular mechanisms underlying this regulation remain poorly understood. Increasing evidence suggests that the mammalian target of rapamycin (mTOR) plays an essential role in this process. Here, we show that Raptor, an essential scaffolding protein of the mTOR complex 1 (mTORC1), becomes phosphorylated on proline-directed sites following activation of the Ras/MAPK pathway. We found that ERK1 and ERK2 interact with Raptor in cells and mediate its phosphorylation in vivo and in vitro. Using mass spectrometry and phosphospecific antibodies, we found three proline-directed residues within Raptor, Ser8, Ser696, and Ser863, which are directly phosphorylated by ERK1/2. Expression of phosphorylation-deficient alleles of Raptor revealed that phosphorylation of these sites by ERK1/2 normally promotes mTORC1 activity and signaling to downstream substrates, such as 4E-BP1. Our data provide a novel regulatory mechanism by which mitogenic and oncogenic activation of the Ras/MAPK pathway promotes mTOR signaling.},
author = {Carriere, Audrey and Romeo, Yves and Acosta-Jaquez, Hugo A. and Moreau, Julie and Bonneil, Eric and Thibault, Pierre and Fingar, Diane C. and Roux, Philippe P.},
doi = {10.1074/jbc.M110.159046},
isbn = {1083-351X (Electronic)$\backslash$r0021-9258 (Linking)},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {21071439},
title = {{ERK1/2 phosphorylate raptor to promote ras-dependent activation of mTOR complex 1 (mTORC1)}},
year = {2011}
}
@misc{Bruggeman2007b,
abstract = {The advent of functional genomics has enabled the molecular biosciences to come a long way towards characterizing the molecular constituents of life. Yet, the challenge for biology overall is to understand how organisms function. By discovering how function arises in dynamic interactions, systems biology addresses the missing links between molecules and physiology. Top-down systems biology identifies molecular interaction networks on the basis of correlated molecular behavior observed in genome-wide 'omics' studies. Bottom-up systems biology examines the mechanisms through which functional properties arise in the interactions of known components. Here, we outline the challenges faced by systems biology and discuss limitations of the top-down and bottom-up approaches, which, despite these limitations, have already led to the discovery of mechanisms and principles that underlie cell function. {\textcopyright} 2006 Elsevier Ltd. All rights reserved.},
author = {Bruggeman, Frank J. and Westerhoff, Hans V.},
booktitle = {Trends in Microbiology},
doi = {10.1016/j.tim.2006.11.003},
isbn = {0966-842X},
issn = {0966842X},
pmid = {17113776},
title = {{The nature of systems biology}},
year = {2007}
}
@article{Kanehisa2008b,
abstract = {KEGG (http://www.genome.jp/kegg/) is a database of biological systems that integrates genomic, chemical and systemic functional information. KEGG provides a reference knowledge base for linking genomes to life through the process of PATHWAY mapping, which is to map, for example, a genomic or transcriptomic content of genes to KEGG reference pathways to infer systemic behaviors of the cell or the organism. In addition, KEGG provides a reference knowledge base for linking genomes to the environment, such as for the analysis of drug-target relationships, through the process of BRITE mapping. KEGG BRITE is an ontology database representing functional hierarchies of various biological objects, including molecules, cells, organisms, diseases and drugs, as well as relationships among them. KEGG PATHWAY is now supplemented with a new global map of metabolic pathways, which is essentially a combined map of about 120 existing pathway maps. In addition, smaller pathway modules are defined and stored in KEGG MODULE that also contains other functional units and complexes. The KEGG resource is being expanded to suit the needs for practical applications. KEGG DRUG contains all approved drugs in the US and Japan, and KEGG DISEASE is a new database linking disease genes, pathways, drugs and diagnostic markers.},
author = {Kanehisa, Minoru and Araki, Michihiro and Goto, Susumu and Hattori, Masahiro and Hirakawa, Mika and Itoh, Masumi and Katayama, Toshiaki and Kawashima, Shuichi and Okuda, Shujiro and Tokimatsu, Toshiaki and Yamanishi, Yoshihiro},
doi = {10.1093/nar/gkm882},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Kanehisa et al. - 2008 - KEGG for linking genomes to life and the environment(2).pdf:pdf},
isbn = {1362-4962 (Electronic)$\backslash$r0305-1048 (Linking)},
issn = {03051048},
journal = {Nucleic Acids Research},
pmid = {18077471},
title = {{KEGG for linking genomes to life and the environment}},
year = {2008}
}
@article{Miele1996a,
abstract = {A quantitative method consisting of the modification of the zero net flux technique was used to determine the extracellular concentration of ascorbate. A carbon paste electrode (CPE) held at constant potential was combined with a microdialysis probe through which various concentrations of ascorbate were locally infused. In experiments with bilateral CPEs, one of which was combined with a dialysis probe, no difference was observed in either basal or stimulated ascorbate currents. Addition of different concentrations of ascorbate to the perfusion fluid produced rapid changes in the voltammetric current due to ascorbate oxidation. Irrespective of the concentration of ascorbate infused, the current returned to basal level when the perfusion was stopped. The return was found to be more rapid after infusion of concentrations of ascorbate higher than the extracellular concentration than after perfusion with ascorbate-free solutions. This demonstrates that homeostasis of ascorbate occurs in vivo. The calculated point of zero net flux was 416 ?? 66 ??M (n = 6). This represents the extracellular concentration of ascorbate.},
author = {Miele, M. and Fillenz, M.},
doi = {10.1016/S0165-0270(96)00094-5},
isbn = {0165-0270 (Print)},
issn = {01650270},
journal = {Journal of Neuroscience Methods},
keywords = {ascorbate,extracellular concentration, in vivo,homeostasis,rat striatum,unanaesthetised rat,voltammetry},
number = {1},
pages = {15--19},
pmid = {8982976},
title = {{In vivo determination of extracellular brain ascorbate}},
volume = {70},
year = {1996}
}
@article{Wang1998a,
abstract = {Initiation factor eIF4E binds to the 5'-cap of eukaryotic mRNAs and plays a key role in the mechanism and regulation of translation. It may be regulated through its own phosphorylation and through inhibitory binding proteins (4E-BPs), which modulate its availability for initiation complex assembly. eIF4E phosphorylation is enhanced by phorbol esters. We show, using specific inhibitors, that this involves both the p38 mitogen-activated protein (MAP) kinase and Erk signaling pathways. Cell stresses such as arsenite and anisomycin and the cytokines tumor necrosis factor-[alpha] and interleukin-1[beta] also cause increased phosphorylation of eIF4E, which is abolished by the specific p38 MAP kinase inhibitor, SB203580. These changes in eIF4E phosphorylation parallel the activity of the eIF4E kinase, Mnk1. However other stresses such as heat shock, sorbitol, and H2O2, which also stimulate p38 MAP kinase and increase Mnk1 activity, do not increase phosphorylation of eIF4E. The latter stresses increase the binding of eIF4E to 4E-BP1, and we show that this blocks the phosphorylation of eIF4E by Mnk1 in vitro, which may explain the absence of an increase in eIF4E phosphorylation under these conditions.},
author = {Wang, Xuemin and Flynn, Andrea and Waskiewicz, Andrew J. and Webb, Benjamin L.J. and Vries, Robert G. and Baines, Ian A. and Cooper, Jonathan A. and Proud, Christopher G.},
doi = {10.1074/jbc.273.16.9373},
isbn = {0021-9258 (Print)},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {9545260},
title = {{The phosphorylation of eukaryotic initiation factor eIF4E in response to phorbol esters, cell stresses, and cytokines is mediated by distinct MAP kinase pathways}},
year = {1998}
}
@article{Sompairac2018,
abstract = {Background: The interplay between metabolic processes and signalling pathways remains poorly understood. Global, detailed and comprehensive reconstructions of human metabolism and signalling pathways exist in the form of molecular maps, but they have never been integrated together. We aim at filling in this gap by creating an integrated resource of both signalling and metabolic pathways allowing a visual exploration of multi-level omics data and study of cross-regulatory circuits between these processes in health and in disease. Results: We combined two comprehensive manually curated network maps. Atlas of Cancer Signalling Network (ACSN), containing mechanisms frequently implicated in cancer; and ReconMap 2.0, a comprehensive reconstruction of human metabolic network. We linked ACSN and ReconMap 2.0 maps via common players and represented the two maps as interconnected layers using the NaviCell platform for maps exploration. In addition, proteins catalysing metabolic reactions in ReconMap 2.0 were not previously visually represented on the map canvas. This precluded visualisation of omics data in the context of ReconMap 2.0. We suggested a solution for displaying protein nodes on the ReconMap 2.0 map in the vicinity of the corresponding reaction or process nodes. This permits multi-omics data visualisation in the context of both map layers. Exploration and shuttling between the two map layers is possible using Google Maps-like features of NaviCell. The integrated ACSN-ReconMap 2.0 resource is accessible online and allows data visualisation through various modes such as markers, heat maps, bar-plots, glyphs and map staining. The integrated resource was applied for comparison of immunoreactive and proliferative ovarian cancer subtypes using transcriptomic, copy number and mutation multi-omics data. A certain number of metabolic and signalling processes specifically deregulated in each of the ovarian cancer sub-types were identified. Conclusions: As knowledge evolves and new omics data becomes more heterogeneous, gathering together existing domains of biology under common platforms is essential. We believe that an integrated ACSN-ReconMap 2.0 resource will help in understanding various disease mechanisms and discovery of new interactions at the intersection of cell signalling and metabolism. In addition, the successful integration of metabolic and signalling networks allows broader systems biology approach application for data interpretation and retrieval of intervention points to tackle simultaneously the key players coordinating signalling and metabolism in human diseases.},
author = {Sompairac, Nicolas and Modamio, Jennifer and Barillot, Emmanuel and Fleming, Ronan M T and Zinovyev, Andrei and Kuperstein, Inna},
file = {:Users/ozlem/Desktop/metabolic and signalling pathway merging.pdf:pdf},
journal = {bioRxiv},
pages = {1--29},
title = {{Metabolic and signalling network map integration: application to cross-talk studies and omics data analysis in cancer}},
url = {http://biorxiv.org/content/early/2018/03/03/274902.abstract},
year = {2018}
}
@article{Soulard2007,
abstract = {mTOR (mammalian Target of Rapamycin) integrates three major inputs—nutrients (amino acids), growth factors (insulin), and cellular energy status—to control several catabolic and anabolic processes that collectively determine cell growth and metabolism. mTOR forms two structurally and functionally distinct multiprotein complex-es, mTORC1 and mTORC2, which correspond to two major branches within the overall signaling network. Both mTORC1 and mTORC2 are atypical serine/threonine kinases. The main components of the network other than the mTORCs are depicted in bright yellow. In response to growth factors, AKT phosphorylates and inactivates TSC1-TSC2 (a heterodimeric GTPase-activating protein), allowing GTP-bound Rheb (a Ras-like GTPase) to activate mTORC1 and possibly mTORC2. Low energy (cel-lular energy status) inhibits mTORC by activating AMPK, which phosphorylates and activates TSC1-TSC2. The pathway by which amino acids, leucine in particular, activate mTORC1 is poorly understood. mTORC1 controls protein synthesis by phosphorylating and inactivating the translational inhibitor 4E-BP and by phosphorylat-ing and activating S6 kinase (S6K). S6K, in addition to phosphorylating various translational targets, also phosphorylates and inhibits insulin receptor substrate 1 (IRS-1) as part of a negative feedback loop that attenuates insulin signaling. mTORC2 promotes cell survival through direct phosphorylation of serine 473 in the hydrophobic motif of AKT. The immunosuppressant rapamycin in complex with FKBP binds and inhibits mTORC1 but not mTORC2. mTOR signaling is deregulated in many diseases including cancer and metabolic disorders. mTOR also mediates nutrient-related processes such as appetite control and aging. RefeRences Avruch, J., Hara, K., Lin, Y., Liu, M., Long, X., Ortiz-Vega, S., and Yonezawa, K. (2006). Insulin and amino-acid regulation of mTOR signaling and kinase activity through the Rheb GTPase. Oncogene 25, 6361–6372. Corradetti, M.N., and Guan, K.L. (2006). Upstream of the mammalian target of rapamycin: do all roads pass through mTOR? Oncogene 25, 6347–6360.},
author = {Soulard, Alexandre and Hall, Michael N.},
doi = {10.1016/j.cell.2007.04.010},
isbn = {0092-8674 (Print)$\backslash$n0092-8674 (Linking)},
issn = {00928674},
journal = {Cell},
pmid = {17449000},
title = {{SnapShot: mTOR Signaling}},
year = {2007}
}
@article{Hynes2003,
abstract = {The filamentous fungus Neurospora crassa, which has played an important role in the development of modern genetics, has several unique genome-defense mechanisms, including a process called repeat-induced point mutation. The draft genome sequence has revealed several unusual features, which suggest that the evolution of N. crassa has been greatly influenced by these defense mechanisms.},
author = {Hynes, Michael J},
doi = {10.1186/gb-2003-4-6-217},
isbn = {1465-6914 (Electronic)$\backslash$n1465-6906 (Linking)},
issn = {1474-760X},
journal = {Genome biology},
keywords = {Animals,Evolution, Molecular,Fungi,Fungi: genetics,Fungi: physiology,Genes, Fungal,Genes, Fungal: genetics,Genes, Fungal: physiology,Genetic Variation,Genetic Variation: genetics,Genetic Variation: physiology,Genome, Fungal,Humans,Neurospora crassa,Neurospora crassa: genetics,Neurospora crassa: physiology},
number = {6},
pages = {217},
pmid = {12801405},
title = {{The Neurospora crassa genome opens up the world of filamentous fungi.}},
url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=193610{\&}tool=pmcentrez{\&}rendertype=abstract},
volume = {4},
year = {2003}
}
@article{Terfve2012b,
author = {Terfve, Camille and Saez-rodriguez, Julio},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Terfve, Saez-rodriguez - 2012 - Training of boolean logic models of signalling networks using prior knowledge networks and perturbation.pdf:pdf},
pages = {1--19},
title = {{Training of boolean logic models of signalling networks using prior knowledge networks and perturbation data with CellNOptR}},
year = {2012}
}
@article{Kleinstiver2016,
abstract = {CRISPR–Cas9 nucleases are widely used for genome editing but can induce unwanted off-target mutations. Existing strategies for reducing genome-wide off-target effects of the widely used Streptococcus pyogenes Cas9 (SpCas9) are imperfect, possessing only partial or unproven efficacies and other limitations that constrain their use. Here we describe SpCas9-HF1, a high-fidelity variant harbouring alterations designed to reduce non-specific DNA contacts. SpCas9-HF1 retains on-target activities comparable to wild-type SpCas9 with {\textgreater}85{\%} of single-guide RNAs (sgRNAs) tested in human cells. Notably, with sgRNAs targeted to standard non-repetitive sequences, SpCas9-HF1 rendered all or nearly all off- target events undetectable by genome-wide break capture and targeted sequencing methods. Even for atypical, repetitive target sites, the vast majority of off-target mutations induced by wild-type SpCas9 were not detected with SpCas9-HF1. With its exceptional precision, SpCas9-HF1 provides an alternative to wild-type SpCas9 for research and therapeutic applications. More broadly, our results suggest a general strategy for optimizing genome-wide specificities of other CRISPR-RNA-guided nucleases.},
archivePrefix = {arXiv},
arxivId = {cs/9605103},
author = {Kleinstiver, Benjamin P. and Pattanayak, Vikram and Prew, Michelle S. and Tsai, Shengdar Q. and Nguyen, Nhu T. and Zheng, Zongli and Joung, J. Keith},
doi = {10.1038/nature16526},
eprint = {9605103},
isbn = {1476-4687 (Electronic)$\backslash$r0028-0836 (Linking)},
issn = {0028-0836},
journal = {Nature},
number = {7587},
pages = {490--495},
pmid = {26735016},
primaryClass = {cs},
title = {{High-fidelity CRISPR–Cas9 nucleases with no detectable genome-wide off-target effects}},
url = {http://www.nature.com/doifinder/10.1038/nature16526},
volume = {529},
year = {2016}
}
@article{Zhou2001,
abstract = {HER-2/neu amplification or overexpression can make cancer cells resistant to apoptosis and promotes their growth. p53 is crucial in regulating cell growth and apoptosis, and is often mutated or deleted in many types of tumour. Moreover, many tumours with a wild-type gene for p53 do not have normal p53 function, suggesting that some oncogenic signals suppress the function of p53. In this study, we show that HER-2/neu-mediated resistance to DNA-damaging agents requires the activation of Akt, which enhances MDM2-mediated ubiquitination and degradation of p53. Akt physically associates with MDM2 and phosphorylates it at Ser166 and Ser186. Phosphorylation of MDM2 enhances its nuclear localization and its interaction with p300, and inhibits its interaction with p19ARF, thus increasing p53 degradation. Our study indicates that blocking the Akt pathway mediated by HER-2/neu would increase the cytotoxic effect of DNA-damaging drugs in tumour cells with wild-type p53.},
author = {Zhou, Binhua P. and Liao, Yong and Xia, Weiya and Zou, Yiyu and Spohn, Bill and Hung, Mien Chie},
doi = {10.1038/ncb1101-973},
isbn = {1465-7392 (Print)$\backslash$r1465-7392 (Linking)},
issn = {14657392},
journal = {Nature Cell Biology},
pmid = {11715018},
title = {{HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation}},
year = {2001}
}
@article{Liu2014,
abstract = {Mammalian target of rapamycin (mTOR) plays essential roles in cell proliferation, survival and metabolism by forming at least two functional distinct multi-protein complexes, mTORC1 and mTORC2. External growth signals can be received and interpreted by mTORC2 and further transduced to mTORC1. On the other hand, mTORC1 can sense inner-cellular physiological cues such as amino acids and energy states and can indirectly suppress mTORC2 activity in part through phosphorylation of its upstream adaptors, IRS-1 or Grb10, under insulin or IGF-1 stimulation conditions. To date, upstream signaling pathways governing mTORC1 activation have been studied extensively, while the mechanisms modulating mTORC2 activity remain largely elusive. We recently reported that Sin1, an essential mTORC2 subunit, was phosphorylated by either Akt or S6K in a cellular context-dependent manner. More importantly, phosphorylation of Sin1 at T86 and T398 led to a dissociation of Sin1 from the functional mTORC2 holo-enzyme, resulting in reduced Akt activity and sensitizing cells to various apoptotic challenges. Notably, an ovarian cancer patient-derived Sin1-R81T mutation abolished Sin1-T86 phosphorylation by disrupting the canonical S6K-phoshorylation motif, thereby bypassing Sin1-phosphorylation-mediated suppression of mTORC2 and leading to sustained Akt signaling to promote tumorigenesis. Our work therefore provided physiological and pathological evidence to reveal the biological significance of Sin1 phosphorylation-mediated suppression of the mTOR/Akt oncogenic signaling, and further suggested that misregulation of this process might contribute to Akt hyper-activation that is frequently observed in human cancers.},
author = {Liu, Pengda and Guo, Jianping and Gan, Wenjian and Wei, Wenyi},
doi = {10.1007/s13238-014-0021-8},
isbn = {1674-800X},
issn = {16748018},
journal = {Protein and Cell},
pmid = {24481632},
title = {{Dual phosphorylation of Sin1 at T86 and T398 negatively regulates mTORC2 complex integrity and activity}},
year = {2014}
}
@article{Hollick2003,
abstract = {6-Aryl-2-morpholin-4-yl-4H-pyran-4-ones and 6-aryl-2-morpholin-4-yl-4H-thiopyran-4-ones were synthesised and evaluated as potential inhibitors of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK). Several compounds in each series exhibited superior activity to the chromenone LY294002, and were of comparable potency to the benzochromenone NU7026 (IC50=0.23 ??M). Importantly, members of both structural classes were found to be selective inhibitors of DNA-PK over related phosphatidylinositol 3-kinase-related kinase (PIKK) family members. A multiple-parallel synthesis approach, employing Suzuki cross-coupling methodology, was utilised to prepare libraries of thiopyran-4-ones with a range of aromatic groups at the 3???- and 4???-positions on the thiopyran-4-one 6-aryl ring. Screening of the libraries resulted in the identification of 6-aryl-2-morpholin-4-yl-4H-thiopyran-4-ones bearing naphthyl or benzo[b]thienyl substituents at the 4???-position, as potent DNA-PK inhibitors with IC50 values in the 0.2-0.4 ??M range. ?? 2003 Elsevier Ltd. All rights reserved.},
author = {Hollick, Jonathan J. and Golding, Bernard T. and Hardcastle, Ian R. and Martin, Niall and Richardson, Caroline and Rigoreau, Laurent J M and Smith, Graeme C M and Griffin, Roger J.},
doi = {10.1016/S0960-894X(03)00652-8},
isbn = {0960-894X (Print)$\backslash$r0960-894X (Linking)},
issn = {0960894X},
journal = {Bioorganic and Medicinal Chemistry Letters},
number = {18},
pages = {3083--3086},
pmid = {12941339},
title = {{2,6-Disubstituted pyran-4-one and thiopyran-4-one inhibitors of DNA-dependent protein kinase (DNA-PK)}},
volume = {13},
year = {2003}
}
@article{Baker2012,
abstract = {As more genomes are assembled from scratch, scientists are struggling to assess and improve their quality.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Baker, Monya},
doi = {10.1038/nmeth.1935},
eprint = {NIHMS150003},
isbn = {1548-7091},
issn = {15487091},
journal = {Nature Methods},
number = {4},
pages = {333--337},
pmid = {22453908},
title = {{De novo genome assembly: What every biologist should know}},
volume = {9},
year = {2012}
}
@misc{Singh2017a,
abstract = {CRISPR-Cas9 is an RNA-mediated adaptive immune system that protects bacteria and archaea from viruses or plasmids. Herein we discuss the recent development of CRISPR-Cas9 into a key technology for genome editing, targeting, and regulation in a wide range of organisms and cell types. It requires a custom designed single guide-RNA (sgRNA), a Cas9 endonuclease, and PAM sequences in the target region. The sgRNA-Cas9 complex binds to its target and creates a double-strand break (DSB) that can be repaired by non-homologous end joining (NHEJ) or by the homology-directed repair (HDR) pathway, modifying or permanently replacing the genomic target sequence. Additionally, we highlight recent advances in the repurposing of CRISPR-Cas9 for repression, activation, and loci imaging. In this review, we underline the current progress and the future potential of the CRISPR-Cas9 system towards biomedical, therapeutic, industrial, and biotechnological applications.},
author = {Singh, Vijai and Braddick, Darren and Dhar, Pawan Kumar},
booktitle = {Gene},
doi = {10.1016/j.gene.2016.11.008},
isbn = {1879-0038 (Electronic)
0378-1119 (Linking)},
issn = {18790038},
keywords = {Activation,CRISPR-Cas9,CRISPRi,Gene therapy,Genome editing,Indel,Repression,sgRNA},
pages = {1--18},
pmid = {27836667},
title = {{Exploring the potential of genome editing CRISPR-Cas9 technology}},
volume = {599},
year = {2017}
}
@article{Binaschi1995,
abstract = {DNA topoisomerases are enzymes that regulate DNA topology and are essential for the integrity of the genetic material during transcription, replication and recombination processes. Inhibitors of the mammalian enzymes are widely used antitumor drugs. They stabilize topoisomerase-DNA cleavable complexes by hindering the DNA relegating step of the catalytic reaction, thus resulting in DNA cleavage stimulation. Investigations on the sequence selectivity of DNA cleavage stimulated by chemically unrelated compounds established that specific nucleotides flanking strand cuts are required for drug action. Moreover, structure-activity relationship studies have identified structural determinants of drug sequence specificities, thus eventually allowing the design of new agents targeted at selected genomic regions. The initial cellular lesion, i.e., the drug-stabilized cleavable complex, is a reversible molecular event; however, how it may lead to cell death remains to be fully clarified. Several laboratories focused in past years on molecular and genetic aspects of drug-activated apoptosis. Irreversible double-stranded DNA breaks, generated from collisions between cleavable complexes and advancing replication forks, were suggested to increase p53 protein levels, thus triggering the cell death program. Other genes were also shown to cooperate in modulating the cell response to drug treatments. Recently, several groups have evaluated the possible prognostic value of topoisomerase II levels in solid tumors and hematopoietic neoplasms. Topoisomerase II inhibitors may also have genotoxic effects. Secondary leukemias, characterized by a translocation between chromosomes 11 and 9, have been reported in disease-free patients after treatments with drug regimens that included anti-topoisomerase II agents. It has been proposed that an impairment of topoisomerase activity may be involved in the molecular pathogenesis of secondary leukemias.},
author = {Binaschi, M and Zunino, F and Capranico, G},
doi = {10.1002/stem.5530130408},
isbn = {1066-5099 (Print)$\backslash$r1066-5099 (Linking)},
issn = {10665099},
journal = {Stem cells},
keywords = {abstract,ar e essential for,dna breakage pharmacophore drug,dna topoisomerases antitumor agents,dna topoisomerases are enzymes,regulate dna topology and,sensitivity tumor,suppressors leukemiaoymphoma,that,the},
number = {4},
pages = {369--379},
pmid = {7549896},
title = {{Mechanism of action of DNA topoisomerase inhibitors.}},
volume = {13},
year = {1995}
}
@article{Umr2018,
author = {Umr, Cnrs and Sup, Ecole Normale},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Umr, Sup - 2018 - bioLQM a java library for the manipulation and conversion of Logical Qualitative Models of biological networks.pdf:pdf},
keywords = {biological networks,computational systems biology,qualitative modeling},
pages = {1--15},
title = {{bioLQM : a java library for the manipulation and conversion of Logical Qualitative Models of biological networks}},
year = {2018}
}
@article{Steffen2007,
abstract = {Herein we introduce CellNetAnalyzer, a toolbox for MATLAB facilitating, in an interactive and visual manner, a comprehensive structural analysis of metabolic, signalling and regulatory networks. The particular strengths of CellNetAnalyzer are methods for functional network analysis, i.e. for characterising functional states, for detecting functional dependencies, for identifying intervention strategies, or for giving qualitative predictions on the effects of perturbations. CellNetAnalyzer extends its predecessor FluxAnalyzer (originally developed for metabolic network and pathway analysis) by a new modelling framework for examining signal-flow networks. Two of the novel methods implemented in CellNetAnalyzer are discussed in more detail regarding algorithmic issues and applications: the computation and analysis (i) of shortest positive and shortest negative paths and circuits in interaction graphs and (ii) of minimal intervention sets in logical networks.},
author = {Steffen, Klamt and J., Saez-Rodriguez and {Ernst D.}, Gilles},
doi = {10.1016/j.jbiotec.2007.02.009},
isbn = {1296312968},
journal = {Journal of Biotechnology},
title = {{BMC Systems biology}},
year = {2007}
}
@article{Lachmann2016a,
abstract = {UNLABELLED The accurate reconstruction of gene regulatory networks from large scale molecular profile datasets represents one of the grand challenges of Systems Biology. The Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) represents one of the most effective tools to accomplish this goal. However, the initial Fixed Bandwidth (FB) implementation is both inefficient and unable to deal with sample sets providing largely uneven coverage of the probability density space. Here, we present a completely new implementation of the algorithm, based on an Adaptive Partitioning strategy (AP) for estimating the Mutual Information. The new AP implementation (ARACNe-AP) achieves a dramatic improvement in computational performance (200× on average) over the previous methodology, while preserving the Mutual Information estimator and the Network inference accuracy of the original algorithm. Given that the previous version of ARACNe is extremely demanding, the new version of the algorithm will allow even researchers with modest computational resources to build complex regulatory networks from hundreds of gene expression profiles. AVAILABILITY AND IMPLEMENTATION A JAVA cross-platform command line executable of ARACNe, together with all source code and a detailed usage guide are freely available on Sourceforge (http://sourceforge.net/projects/aracne-ap). JAVA version 8 or higher is required. CONTACT califano@c2b2.columbia.edu SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.},
author = {Lachmann, Alexander and Giorgi, Federico M. and Lopez, Gonzalo and Califano, Andrea},
doi = {10.1093/bioinformatics/btw216},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Lachmann et al. - 2016 - ARACNe-AP Gene network reverse engineering through adaptive partitioning inference of mutual information(2).pdf:pdf},
isbn = {13674811 (Electronic)},
issn = {14602059},
journal = {Bioinformatics},
number = {14},
pages = {2233--2235},
pmid = {27153652},
title = {{ARACNe-AP: Gene network reverse engineering through adaptive partitioning inference of mutual information}},
volume = {32},
year = {2016}
}
@article{Jensen1999,
abstract = {90-kDa ribosomal S6 kinase-2 (RSK2) belongs to a family of growth factor-activated serine/threonine kinases composed of two kinase domains connected by a regulatory linker region. The N-terminal kinase of RSK2 is involved in substrate phosphorylation. Its activation requires phosphorylation of the linker region at Ser369, catalyzed by extracellular signal-regulated kinase (ERK), and at Ser386, catalyzed by the C-terminal kinase, after its activation by ERK. In addition, the N-terminal kinase must be phosphorylated at Ser227 in the activation loop by an as yet unidentified kinase. Here, we show that the isolated N-terminal kinase of RSK2 (amino acids 1-360) is phosphorylated at Ser227 by PDK1, a constitutively active kinase, leading to 100-fold stimulation of kinase activity. In COS7 cells, ectopic PDK1 induced the phosphorylation of full-length RSK2 at Ser227and Ser386, without involvement of ERK, leading to partial activation of RSK2. Similarly, two other members of the RSK family, RSK1 and RSK3, were partially activated by PDK1 in COS7 cells. Finally, our data indicate that full activation of RSK2 by growth factor requires the cooperation of ERK and PDK1 through phosphorylation of Ser227, Ser369, and Ser386. Our study extend recent findings which implicate PDK1 in the activation of protein kinases B and C and p70S6K, suggesting that PDK1 controls several major growth factor-activated signal transduction pathways.},
author = {Jensen, Claus J. and Buch, Maj Britt and Krag, Thomas O. and Hemmings, Brian A. and Gammeltoft, Steen and Fr{\"{o}}din, Morten},
doi = {10.1074/jbc.274.38.27168},
isbn = {2716827176},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {10480933},
title = {{90-kDa ribosomal S6 kinase is phosphorylated and activated by 3- phosphoinositide-dependent protein kinase-1}},
year = {1999}
}
@article{GuijinZhang1997,
abstract = {A rapid procedure for the extraction and assay of $\gamma$-aminobutyric acid (GABA) is described. The extraction procedure prevents rapid GABA accumulation during the sampling of tissue for analysis. It also removes over 95{\%} of pigments absorbing at 340 nm which otherwise reduce the sensitivity of the spectrophotometric coupled enzyme assay. The absorbance increase at 340 nm was linear for GABA levels ranging from 10 to 100 nmol per cuvette.},
author = {{Guijin Zhang} and Bown, Alan W.},
doi = {10.1016/S0031-9422(96)00626-7},
issn = {00319422},
journal = {Phytochemistry},
keywords = {7-aminobutyric acid,deter-,gaba,index--glycine max,leguminosae,soybean},
number = {6},
pages = {1007--1009},
title = {{The rapid determination of $\gamma$-aminobutyric acid}},
volume = {44},
year = {1997}
}
@article{Guertin2006,
abstract = {The mTOR kinase controls cell growth, proliferation, and survival through two distinct multiprotein complexes, mTORC1 and mTORC2. mTOR and mLST8 are in both complexes, while raptor and rictor are part of only mTORC1 and mTORC2, respectively. To investigate mTORC1 and mTORC2 function in vivo, we generated mice deficient for raptor, rictor, or mLST8. Like mice null for mTOR, those lacking raptor die early in development. However, mLST8 null embryos survive until e10.5 and resemble embryos missing rictor. mLST8 is necessary to maintain the rictor-mTOR, but not the raptor-mTOR, interaction, and both mLST8 and rictor are required for the hydrophobic motif phosphorylation of Akt/PKB and PKC alpha, but not S6K1. Furthermore, insulin signaling to FOXO3, but not to TSC2 or GSK3 beta, requires mLST8 and rictor. Thus, mTORC1 function is essential in early development, mLST8 is required only for mTORC2 signaling, and mTORC2 is a necessary component of the Akt-FOXO and PKC alpha pathways.},
author = {Guertin, David A. and Stevens, Deanna M. and Thoreen, Carson C. and Burds, Aurora A. and Kalaany, Nada Y. and Moffat, Jason and Brown, Michael and Fitzgerald, Kevin J. and Sabatini, David M.},
doi = {10.1016/j.devcel.2006.10.007},
isbn = {1534-5807},
issn = {15345807},
journal = {Developmental Cell},
keywords = {DEVBIO,SIGNALING},
pmid = {17141160},
title = {{Ablation in Mice of the mTORC Components raptor, rictor, or mLST8 Reveals??that mTORC2 Is Required for Signaling to Akt-FOXO and PKCa, but Not S6K1}},
year = {2006}
}
@techreport{Siebert,
abstract = {Starting from the logical description of gene regulatory networks developed by R. Thomas, we introduce an enhanced modelling approach based on timed au-tomata. We obtain a refined qualitative description of the dynamical behaviour by exploiting not only information on ratios of kinetic parameters related to synthesis and decay, but also constraints on the time delays associated with the operations of the system. We develop a formal framework for handling such temporal constraints using timed automata, discuss the relationship with the original Thomas formalism , and demonstrate the potential of our approach by analysing an illustrative gene regulatory network of bacteriophage $\lambda$.},
author = {Siebert, Heike and Bockmayr, Alexander},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Siebert, Bockmayr - Unknown - Temporal Constraints in the Logical Analysis of Regulatory Networks.pdf:pdf},
title = {{Temporal Constraints in the Logical Analysis of Regulatory Networks}}
}
@article{Smolinska2012,
abstract = {Metabolomics is the discipline where endogenous and exogenous metabolites are assessed, identified and quantified in different biological samples. Metabolites are crucial components of biological system and highly informative about its functional state, due to their closeness to functional endpoints and to the organism's phenotypes. Nuclear Magnetic Resonance (NMR) spectroscopy, next to Mass Spectrometry (MS), is one of the main metabolomics analytical platforms. The technological developments in the field of NMR spectroscopy have enabled the identification and quantitative measurement of the many metabolites in a single sample of biofluids in a non-targeted and non-destructive manner. Combination of NMR spectra of biofluids and pattern recognition methods has driven forward the application of metabolomics in the field of biomarker discovery. The importance of metabolomics in diagnostics, e.g. in identifying biomarkers or defining pathological status, has been growing exponentially as evidenced by the number of published papers. In this review, we describe the developments in data acquisition and multivariate analysis of NMR-based metabolomics data, with particular emphasis on the metabolomics of Cerebrospinal Fluid (CSF) and biomarker discovery in Multiple Sclerosis (MScl). {\textcopyright} 2012 Elsevier B.V.},
author = {Smolinska, Agnieszka and Blanchet, Lionel and Buydens, Lutgarde M C and Wijmenga, Sybren S.},
doi = {10.1016/j.aca.2012.05.049},
isbn = {0003-2670},
issn = {00032670},
journal = {Analytica Chimica Acta},
keywords = {Biomarker discovery,Metabolomics,Multiple Sclerosis,NMR,Pattern recognition,Preprocessing},
pages = {82--97},
pmid = {23062430},
title = {{NMR and pattern recognition methods in metabolomics: From data acquisition to biomarker discovery: A review}},
url = {http://dx.doi.org/10.1016/j.aca.2012.05.049},
volume = {750},
year = {2012}
}
@article{Nersisyan2014,
abstract = {The KEGG pathway database is a widely accepted source for biomolecular pathway maps. In this paper we present the CyKEGGParser app ( http://apps.cytoscape.org/apps/cykeggparser) for Cytoscape 3 that allows manipulation with KEGG pathway maps. Along with basic functionalities for pathway retrieval, visualization and export in KGML and BioPAX formats, the app provides unique features for computer-assisted adjustment of inconsistencies in KEGG pathway KGML files and generation of tissue- and protein-protein interaction specific pathways. We demonstrate that using biological context-specific KEGG pathways created with CyKEGGParser makes systems biology analysis more sensitive and appropriate compared to original pathways.},
author = {Nersisyan, Lilit and Samsonyan, Ruben and Arakelyan, Arsen},
doi = {10.12688/f1000research.4410.2},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Nersisyan, Samsonyan, Arakelyan - 2014 - CyKEGGParser tailoring KEGG pathways to fit into systems biology analysis workflows.pdf:pdf},
isbn = {2046-1402 (Electronic)$\backslash$r2046-1402 (Linking)},
issn = {2046-1402},
journal = {F1000Research},
number = {0},
pages = {1--12},
pmid = {25383185},
title = {{CyKEGGParser: tailoring KEGG pathways to fit into systems biology analysis workflows}},
url = {http://f1000research.com/articles/3-145/v2},
year = {2014}
}
@article{Durai2016,
abstract = {Motivation: De novo transcriptome assembly is an integral part for many RNA-seq workflows. Common applications include sequencing of non-model organisms, cancer or meta transcriptomes. Most de novo transcriptome assemblers use the de Bruijn graph (DBG) as the underlying data structure. The quality of the assemblies produced by such assemblers is highly influenced by the exact word length k. As such no single kmer value leads to optimal results. Instead, DBGs over different kmer values are built and the assemblies are merged to improve sensitivity. However, no studies have investigated thoroughly the problem of automatically learning at which kmer value to stop the assembly. Instead a suboptimal selection of kmer values is often used in practice. Results: Here we investigate the contribution of a single kmer value in a multi-kmer based assembly approach. We find that a comparative clustering of related assemblies can be used to estimate the importance of an additional kmer assembly. Using a model fit based algorithm we predict the kmer value at which no further assemblies are necessary. Our approach is tested with different de novo assemblers for datasets with different coverage values and read lengths. Further, we suggest a simple post processing step that significantly improves the quality of multi-kmer assemblies. Conclusion: We provide an automatic method for limiting the number of kmer values without a significant loss in assembly quality but with savings in assembly time. This is a step forward to making multi-kmer methods more reliable and easier to use.},
author = {Durai, Dilip A. and Schulz, Marcel H.},
doi = {10.1093/bioinformatics/btw217},
isbn = {1367-4803},
issn = {14602059},
journal = {Bioinformatics},
number = {11},
pages = {1670--1677},
pmid = {27153653},
title = {{Informed kmer selection for de novo transcriptome assembly}},
volume = {32},
year = {2016}
}
@article{Silva2004,
abstract = {The signal transducers and activators of transcription (STATs) were originally identified in the signaling pathway activated by the nontyrosine kinase containing cytokine receptors. The role of these STATs in hematopoietic cell signaling has been well described. In the case of cytokine receptors, activation of STAT tyrosine phosphorylation occurs through ligand-induced recruitment, and activation of the intracellular JAK kinases. However, STATs can also be activated by growth factor receptors, particularly the EGFR; as well as by members of the Src Family of Kinases (SFKs), particularly c-Src. In many cases, there is a differential activation of the STATs by these tyrosine kinases as compared to activation by the cytokine receptors. This difference provides for the potential of unique actions of STATs in response to growth factor receptor and SFK activation. Since there are many cancers in which SFKs and c-Src in particular, are co-overexpressed with growth factor receptors, it is not surprising that STATs play an important role in the tumorigenesis process induced by c-Src. The activation paradigm and role of STATs in these cancers, with particular emphasis on breast cancer models, is discussed.},
author = {Silva, Corinne M.},
doi = {10.1038/sj.onc.1208159},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/1208159.pdf:pdf},
isbn = {0950-9232 (Print)$\backslash$r0950-9232 (Linking)},
issn = {09509232},
journal = {Oncogene},
keywords = {Breast cancer,STAT3,STAT5,Tumorigenesis,c-Src},
number = {48 REV. ISS. 7},
pages = {8017--8023},
pmid = {15489919},
title = {{Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis}},
volume = {23},
year = {2004}
}
@article{Steinway2015,
author = {Steinway, Steven Nathaniel and Gomez, Jorge and Za{\~{n}}udo, Tejeda and Michel, Paul J and Feith, David J and Loughran, Thomas P and Albert, Reka},
doi = {10.1038/npjsba.2015.14},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/Steinway2015.pdf:pdf},
journal = {Nature Publishing Group},
number = {June},
pages = {1--12},
publisher = {Nature Publishing Group},
title = {{Combinatorial interventions inhibit TGF $\beta$ -driven epithelial-to-mesenchymal transition and support hybrid cellular phenotypes}},
url = {http://dx.doi.org/10.1038/npjsba.2015.14},
year = {2015}
}
@article{Iniguez2017,
abstract = {The protein diversity that exists today has resulted from various evolutionary processes. It is well known that gene duplication (GD) along with the accumulation of mutations are responsible, among other factors, for an increase in the number of different proteins. The gene structure in eukaryotes requires the removal of non-coding sequences, introns, to produce mature mRNAs. This process, known as cis-splicing, referred to here as splicing, is regulated by several factors which can lead to numerous splicing arrangements, commonly designated as alternative splicing (AS). AS, producing several transcripts isoforms form a single gene, also increases the protein diversity. However, the evolution and manner for increasing protein variation differs between AS and GD. An important question is how are patterns of AS affected after a GD event. Here, we review the current knowledge of AS and GD, focusing on their evolutionary relationship. These two processes are now considered the main contributors to the increasing protein diversity and therefore their relationship is a relevant, yet understudied, area of evolutionary study.},
author = {I{\~{n}}iguez, Luis P. and Hern{\'{a}}ndez, Georgina},
doi = {10.3389/fgene.2017.00014},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/I{\~{n}}iguez, Hern{\'{a}}ndez - 2017 - The evolutionary relationship between alternative splicing and gene duplication.pdf:pdf},
isbn = {1664-8021},
issn = {16648021},
journal = {Frontiers in Genetics},
keywords = {Alternative splicing,Evolution,Gene duplication,MRNA isoforms,Polyploidy},
number = {FEB},
pages = {1--7},
pmid = {28261262},
title = {{The evolutionary relationship between alternative splicing and gene duplication}},
volume = {8},
year = {2017}
}
@article{Gresset2010,
abstract = {The lipase activity of most phospholipases C (PLCs) is basally repressed by a highly degenerate and mostly disordered X/Y linker inserted within the catalytic domain. Release of this auto-inhibition is driven by electrostatic repulsion between the plasma membrane and the electronegative X/Y linker. In contrast, PLC-$\gamma$ isozymes (PLC-$\gamma$1 and -$\gamma$2) are structurally distinct from other PLCs because multiple domains are present in their X/Y linker. Moreover, although many tyrosine kinases directly phosphorylate PLC-$\gamma$ isozymes to enhance their lipase activity, the underlying molecular mechanism of this activation remains unclear. Here we define the mechanism for the unique regulation of PLC-$\gamma$ isozymes by their X/Y linker. Specifically, we identify the C-terminal SH2 domain within the X/Y linker as the critical determinant for auto-inhibition. Tyrosine phosphorylation of the X/Y linker mediates high affinity intramolecular interaction with the C-terminal SH2 domain that is coupled to a large conformational rearrangement and release of auto-inhibition. Consequently, PLC-$\gamma$ isozymes link phosphorylation to phospholipase activation by elaborating upon primordial regulatory mechanisms found in other PLCs.},
author = {Gresset, Aurelie and Hicks, Stephanie N. and Harden, T. Kendall and Sondek, John},
doi = {10.1074/jbc.M110.166512},
isbn = {1083-351X (Electronic)$\backslash$r0021-9258 (Linking)},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {20807769},
title = {{Mechanism of phosphorylation-induced activation of phospholipase C-$\gamma$ isozymes}},
year = {2010}
}
@misc{Ma2009,
abstract = {Translational control is widely used to regulate gene expression. This mode of regulation is especially relevant in situations where transcription is silent or when local control over protein accumulation is required. Although many examples of translational regulation have been described, only a few are beginning to be mechanistically understood. Instead of providing a comprehensive account of the examples that are known at present, we discuss instructive cases that serve as paradigms for different modes of translational control.},
author = {Ma, Xiaoju Max and Blenis, John},
booktitle = {Nature Reviews Molecular Cell Biology},
doi = {10.1038/nrm2672},
isbn = {1471-0072 (Print)$\backslash$r1471-0072 (Linking)},
issn = {14710072},
pmid = {15459663},
title = {{Molecular mechanisms of mTOR-mediated translational control}},
year = {2009}
}
@article{Koziol2005,
abstract = {Yeast (Saccharomyces cerevisiae) mutants lacking CuZnSOD have been reported to be hypersensitive to hypertonic media and to show increased oxidative damage. This study demonstrates that hypertonic medium (containing 0.8 M NaCI) increases the generation of superoxide and other reactive species in yeast cells. Other sequelae of exposure to hypertonic medium include oxidation of cellular low-molecular weight thiols and decrease in total antioxidant capacity of cellular extracts. {\&}UDelta; sod1 mutant is more sensitive than a wild-type strain to colony growth inhibition on a hypertonic medium. Anaerobic conditions, ascorbate, glutathione, cysteine and dithiothreitol are able to ameliorate this growth inhibition but a range of other antioxidants does not protect. The protective ability of the antioxidants does not correlate with the rate of their reactions with superoxide but seems to be conditioned by low redox potential for one-electron oxidation of free radicals of the antioxidants. It suggests that repair of low-redox potential targets rather than prevention of their damage by superoxide is important in the antioxidant protection against oxidative stress induced by hypertonic conditions},
author = {Koziol, Sabina and Zagulski, Marek and Bilinski, Tomasz and Bartosz, Grzegorz},
doi = {10.1080/10715760500045855},
isbn = {1071-5762},
issn = {10715762},
journal = {Free Radical Research},
keywords = {Osmotic stress,Oxidative stress,Saccharomyces cerevisiae,Superoxide,Superoxide dismutase,Yeast},
number = {4},
pages = {365--371},
pmid = {12583},
title = {{Antioxidants protect the yeast Saccharomyces cerevisiae against hypertonic stress}},
volume = {39},
year = {2005}
}
@misc{Perry2009,
abstract = {Methods and advances for monitoring neurotransmitters in vivo or for tissue analysis of neurotransmitters over the last five years are reviewed. The review is organized primarily by neurotransmitter type. Transmitter and related compounds may be monitored by either in vivo sampling coupled to analytical methods or implanted sensors. Sampling is primarily performed using microdialysis, but low-flow push-pull perfusion may offer advantages of spatial resolution while minimizing the tissue disruption associated with higher flow rates. Analytical techniques coupled to these sampling methods include liquid chromatography, capillary electrophoresis, enzyme assays, sensors, and mass spectrometry. Methods for the detection of amino acid, monoamine, neuropeptide, acetylcholine, nucleoside, and soluble gas neurotransmitters have been developed and improved upon. Advances in the speed and sensitivity of these methods have enabled improvements in temporal resolution and increased the number of compounds detectable. Similar advances have enabled improved detection at tissue samples, with a substantial emphasis on single cell and other small samples. Sensors provide excellent temporal and spatial resolution for in vivo monitoring. Advances in application to catecholamines, indoleamines, and amino acids have been prominent. Improvements in stability, sensitivity, and selectivity of the sensors have been of paramount interest. ?? 2009 Elsevier B.V. All rights reserved.},
author = {Perry, Maura and Li, Qiang and Kennedy, Robert T.},
booktitle = {Analytica Chimica Acta},
doi = {10.1016/j.aca.2009.08.038},
isbn = {0003-2670},
issn = {00032670},
keywords = {Biosensor,Microdialysis,Neurotransmitter},
number = {1},
pages = {1--22},
pmid = {19800472},
title = {{Review of recent advances in analytical techniques for the determination of neurotransmitters}},
volume = {653},
year = {2009}
}
@article{Aguilera2010,
abstract = {We used adaptive evolution to improve freeze tolerance of industrial baker's yeast. Our hypothesis was that adaptation to low temperature is accompanied by enhanced resistance of yeast to freezing. Based on this hypothesis, yeast was propagated in a flour-free liquid dough model system, which contained sorbitol and NaCl, by successive batch refreshments maintained constantly at 12°C over at least 200 generations. Relative to the parental population, the maximal growth rate (µ(max)) under the restrictive conditions, increased gradually over the time course of the experiment. This increase was accompanied by enhanced freeze tolerance. However, these changes were not the consequence of genetic adaptation to low temperature, a fact that was confirmed by prolonged selection of yeast cells in YPD at 12°C. Instead, the experimental populations showed a progressive increase in NaCl tolerance. This phenotype was likely achieved at the expense of others traits, since evolved cells showed a ploidy reduction, a defect in the glucose derepression mechanism and a loss in their ability to utilize gluconeogenic carbon sources. We discuss the genetic flexibility of S. cerevisiae in terms of adaptation to the multiple constraints of the experimental design applied to drive adaptive evolution and the technologically advantageous phenotype of the evolved population.},
author = {Aguilera, Jaime and Andreu, Pasqual and Randez-Gil, Francisca and Prieto, Jose Antonio},
doi = {10.1111/j.1751-7915.2009.00136.x},
isbn = {1751-7915 (Electronic)$\backslash$r1751-7915 (Linking)},
issn = {17517907},
journal = {Microbial Biotechnology},
number = {2},
pages = {210--221},
pmid = {21255321},
title = {{Adaptive evolution of baker's yeast in a dough-like environment enhances freeze and salinity tolerance}},
volume = {3},
year = {2010}
}
@article{Lipfert2007,
abstract = {Small-angle X-ray scattering (SAXS) is increasingly used to characterize the structure and interactions of biological macromolecules and their complexes in solution. Although still a low-resolution technique, the advent of high-flux synchrotron sources and the development of algorithms for the reconstruction of 3-D electron density maps from 1-D scattering profiles have made possible the generation of useful low-resolution molecular models from SAXS data. Furthermore, SAXS is well suited for the study of unfolded or partially folded conformational ensembles as a function of time or solution conditions. Here, we review recently developed algorithms for 3-D structure modeling and applications to protein complexes. Furthermore, we discuss the emerging use of SAXS as a tool to study membrane protein-detergent complexes. SAXS is proving useful to study the folding of functional RNA molecules, and finally we discuss uses of SAXS to study ensembles of denatured proteins.},
author = {Lipfert, Jan and Doniach, Sebastian},
doi = {10.1146/annurev.biophys.36.040306.132655},
isbn = {1056-8700 (Print)$\backslash$n1056-8700 (Linking)},
issn = {1056-8700},
journal = {Annual Review of Biophysics and Biomolecular Structure},
number = {1},
pages = {307--327},
pmid = {17284163},
title = {{Small-Angle X-Ray Scattering from RNA, Proteins, and Protein Complexes}},
url = {http://www.annualreviews.org/doi/10.1146/annurev.biophys.36.040306.132655},
volume = {36},
year = {2007}
}
@article{LeNovere2015a,
abstract = {Behaviours of complex biomolecular systems are often irreducible to the elementary properties of their individual components. Explanatory and predictive mathematical models are therefore useful for fully understanding and precisely engineering cellular functions. The development and analyses of these models require their adaptation to the problems that need to be solved and the type and amount of available genetic or molecular data. Quantitative and logic modelling are among the main methods currently used to model molecular and gene networks. Each approach comes with inherent advantages and weaknesses. Recent developments show that hybrid approaches will become essential for further progress in synthetic biology and in the development of virtual organisms.},
author = {{Le Novere}, Nicolas},
doi = {10.1038/nrg3885},
file = {:Users/ozlem/Desktop/papers/Nov{\`{e}}re2015.pdf:pdf},
isbn = {1471-0056$\backslash$r1471-0064},
issn = {14710064},
journal = {Nature Reviews Genetics},
number = {3},
pages = {146--158},
pmid = {25645874},
title = {{Quantitative and logic modelling of molecular and gene networks}},
volume = {16},
year = {2015}
}
@article{Richards2001,
abstract = {RSK is a serine/threonine kinase containing two distinct catalytic domains. Found at the terminus of the Ras/extracellular signal-regulated kinase (ERK)–mitogen-activated protein kinase (MAPK) kinase cascade, mitogen-stimulated ribosomal S6 kinase (RSK) activity requires multiple inputs. These inputs include phosphorylation of the C-terminal kinase domain activation loop by ERK1/2 and phosphorylation of the N-terminal kinase domain activation loop by phosphoinositide-dependent protein kinase-1 (PDK1). Previous work has shown that upon mitogen stimulation, RSK accumulates in the nucleus. Here we show that prior to nuclear translocation, epidermal growth factor-stimulated RSK1 transiently associates with the plasma membrane. Myristylation of wild-type RSK1 results in an activated enzyme in the absence of added growth factors. When RSK is truncated at the C terminus, the characterized ERK docking is removed and RSK phosphotransferase activity is completely abolished. When myristylated, however, this myristylated C-terminal truncated form (myrCTT) is activated at a level equivalent to myristylated wild-type (myrWT) RSK. Both myrWT RSK and myrCTT RSK can signal to the RSK substrate c-Fos in the absence of mitogen activation. Unlike myrWT RSK, myrCTT RSK is not further activated by serum. Only the myristylated RSK proteins are basally phosphorylated on avian RSK1 serine 381, a site critical for RSK activity. The myristylated and unmyristylated RSK constructs interact with PDK1 upon mitogen stimulation, and this interaction is insensitive to the MEK inhibitor UO126. Because a kinase-inactive CTT RSK can be constitutively activated by targeting to the membrane, we propose that ERK may have a dual role in early RSK activation events: preliminary phosphorylation of RSK and escorting RSK to a membrane-associated complex, where additional MEK/ERK-independent activating inputs are encountered.},
author = {Richards, Stephanie A and Dreisbach, Valley C and Murphy, Leon O and Blenis, John},
doi = {10.1128/MCB.21.21.7470-7480.2001},
journal = {Molecular and Cellular Biology},
month = {nov},
number = {21},
pages = {7470 LP  -- 7480},
title = {{Characterization of Regulatory Events Associated with Membrane Targeting of p90 Ribosomal S6 Kinase 1}},
url = {http://mcb.asm.org/content/21/21/7470.abstract},
volume = {21},
year = {2001}
}
@article{Kim2003,
abstract = {mTOR and raptor are components of a signaling pathway that regulates mammalian cell growth in response to nutrients and growth factors. Here, we identify a member of this pathway, a protein named G$\beta$L that binds to the kinase domain of mTOR and stabilizes the interaction of raptor with mTOR. Like mTOR and raptor, G$\beta$L participates in nutrient- and growth factor-mediated signaling to S6K1, a downstream effector of mTOR, and in the control of cell size. The binding of G$\beta$L to mTOR strongly stimulates the kinase activity of mTOR toward S6K1 and 4E-BP1, an effect reversed by the stable interaction of raptor with mTOR. Interestingly, nutrients and rapamycin regulate the association between mTOR and raptor only in complexes that also contain G$\beta$L. Thus, we propose that the opposing effects on mTOR activity of the G$\beta$L- and raptor-mediated interactions regulate the mTOR pathway.},
author = {Kim, Do Hyung and Sarbassov, Dos D. and Ali, Siraj M. and Latek, Robert R. and Guntur, Kalyani V.P. and Erdjument-Bromage, Hediye and Tempst, Paul and Sabatini, David M.},
doi = {10.1016/S1097-2765(03)00114-X},
isbn = {1097-2765 (Print)$\backslash$n1097-2765 (Linking)},
issn = {10972765},
journal = {Molecular Cell},
pmid = {12718876},
title = {{G$\beta$L, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR}},
year = {2003}
}
@article{Crotti2001,
abstract = {Yeast cells were permeabilized by incubation in 0.8 M sorbitol followed by suspension in dilute buffer. A preincubation with 2-mercaptoethanol was also included for optimal permeabilization. More than 90{\%} of the treated cells were stainable with methylene blue. Determinations of cell wall-synthesizing enzymes (beta(1 --{\textgreater} 3)glucan and chitin synthases) and cytosolic enzymes in permeabilized cells yielded similar or higher activities than those in cell extracts. With chitin synthase III, the activity obtained with cells was 4- to 6-fold higher than in membrane preparations. Little protein leaks from the cells during permeabilization; yet the cells appear to be readily permeable to substrates and even proteins. Thus, these preparations may be of wide use for the study of enzymes and of biological processes in situ.},
author = {Crotti, Luciana B. and Drgon, Tom{\'{a}}s and Cabib, Enrico},
doi = {10.1006/abio.2001.5051},
isbn = {0003-2697 (Print) 0003-2697 (Linking)},
issn = {00032697},
journal = {Analytical Biochemistry},
number = {1},
pages = {8--16},
pmid = {11319811},
title = {{Yeast Cell Permeabilization by Osmotic Shock Allows Determination of Enzymatic Activities in Situ}},
url = {http://linkinghub.elsevier.com/retrieve/pii/S0003269701950511},
volume = {292},
year = {2001}
}
@misc{Kitano2005a,
abstract = {With the increased interest in understanding biological networks, such as protein-protein interaction networks and gene regulatory networks, methods for representing and communicating such networks in both human- and machine-readable form have become increasingly important. Although there has been significant progress in machine-readable representation of networks, as exemplified by the Systems Biology Mark-up Language (SBML) (http://www.sbml.org) issues in human-readable representation have been largely ignored. This article discusses human-readable diagrammatic representations and proposes a set of notations that enhances the formality and richness of the information represented. The process diagram is a fully state transition-based diagram that can be translated into machine-readable forms such as SBML in a straightforward way. It is supported by CellDesigner, a diagrammatic network editing software (http://www.celldesigner.org/), and has been used to represent a variety of networks of various sizes (from only a few components to several hundred components).},
author = {Kitano, Hiroaki and Funahashi, Akira and Matsuoka, Yukiko and Oda, Kanae},
booktitle = {Nature Biotechnology},
doi = {10.1038/nbt1111},
file = {:Users/ozlem/Dropbox/papers/Biological Networks/nbt1111.pdf:pdf},
isbn = {1087-0156 (Print)$\backslash$r1087-0156 (Linking)},
issn = {10870156},
pmid = {16082367},
title = {{Using process diagrams for the graphical representation of biological networks}},
year = {2005}
}
@article{Morton2003,
abstract = {We have used phospho‐specific antibodies to re‐examine the multisite phosphorylation of c‐Jun in murine RAW macrophages and embryonic fibroblasts. Our results indicate that JNK isoforms are required and sufficient for the phosphorylation of Thr91 and Thr93, as well as the phosphorylation of Ser63 and Ser73, in response to LPS or anisomycin in macrophages and TNF$\alpha$ or anisomycin in fibroblasts. However, the phorbol ester (TPA) and EGF‐induced phosphorylation of Ser63 and Ser73 is mediated by ERK1/ERK2, as well as JNK1/JNK2, in fibroblasts from wild‐type mice and by ERK1/ERK2 alone in fibroblasts from JNK‐deficient mice. The phosphorylation of Thr239 is catalysed by GSK3 and the phosphorylation of Ser243 by an as yet unidentified protein kinase. The inhibition of GSK3 is not required for the dephosphorylation of Thr239 in response to LPS, and nor is the phosphorylation of Thr91 and Thr93 required for the TPA‐ or EGF‐induced dephosphorylation of Thr239 in fibroblasts. The agonist‐induced dephosphorylation of Thr239 may involve a conformational change that exposes Thr239 to dephosphorylation and/or the activation of a Thr239 phosphatase.},
author = {Morton, Simon and Davis, Roger J and McLaren, Ann and Cohen, Philip},
doi = {10.1093/emboj/cdg388},
journal = {The EMBO Journal},
month = {aug},
number = {15},
pages = {3876 LP  -- 3886},
title = {{A reinvestigation of the multisite phosphorylation of the transcription factor c‐Jun}},
url = {http://emboj.embopress.org/content/22/15/3876.abstract},
volume = {22},
year = {2003}
}
@article{Molinelli2013,
abstract = {We present a powerful experimental-computational technology for inferring network models that predict the response of cells to perturbations, and that may be useful in the design of combinatorial therapy against cancer. The experiments are systematic series of perturbations of cancer cell lines by targeted drugs, singly or in combination. The response to perturbation is quantified in terms of relative changes in the measured levels of proteins, phospho-proteins and cellular phenotypes such as viability. Computational network models are derived de novo, i.e., without prior knowledge of signaling pathways, and are based on simple non-linear differential equations. The prohibitively large solution space of all possible network models is explored efficiently using a probabilistic algorithm, Belief Propagation (BP), which is three orders of magnitude faster than standard Monte Carlo methods. Explicit executable models are derived for a set of perturbation experiments in SKMEL-133 melanoma cell lines, which are resistant to the therapeutically important inhibitor of RAF kinase. The resulting network models reproduce and extend known pathway biology. They empower potential discoveries of new molecular interactions and predict efficacious novel drug perturbations, such as the inhibition of PLK1, which is verified experimentally. This technology is suitable for application to larger systems in diverse areas of molecular biology.},
archivePrefix = {arXiv},
arxivId = {1308.5193},
author = {Molinelli, Evan J. and Korkut, Anil and Wang, Weiqing and Miller, Martin L. and Gauthier, Nicholas P. and Jing, Xiaohong and Kaushik, Poorvi and He, Qin and Mills, Gordon and Solit, David B. and Pratilas, Christine A. and Weigt, Martin and Braunstein, Alfredo and Pagnani, Andrea and Zecchina, Riccardo and Sander, Chris},
doi = {10.1371/journal.pcbi.1003290},
eprint = {1308.5193},
isbn = {10.1371/journal.pcbi.1003290},
issn = {1553734X},
journal = {PLoS Computational Biology},
pmid = {24367245},
title = {{Perturbation Biology: Inferring Signaling Networks in Cellular Systems}},
year = {2013}
}
@article{Kuperstein2015a,
abstract = {Cancerogenesis is driven by mutations leading to aberrant functioning of a complex network of molecular interactions and simultaneously affecting multiple cellular functions. Therefore, the successful application of bioinformatics and systems biology methods for analysis of high-throughput data in cancer research heavily depends on availability of global and detailed reconstructions of signalling networks amenable for computational analysis. We present here the Atlas of Cancer Signalling Network (ACSN), an interactive and comprehensive map of molecular mechanisms implicated in cancer. The resource includes tools for map navigation, visualization and analysis of molecular data in the context of signalling network maps. Constructing and updating ACSN involves careful manual curation of molecular biology literature and participation of experts in the corresponding fields. The cancer-oriented content of ACSN is completely original and covers major mechanisms involved in cancer progression, including DNA repair, cell survival, apoptosis, cell cycle, EMT and cell motility. Cell signalling mechanisms are depicted in detail, together creating a seamless 'geographic-like' map of molecular interactions frequently deregulated in cancer. The map is browsable using NaviCell web interface using the Google Maps engine and semantic zooming principle. The associated web-blog provides a forum for commenting and curating the ACSN content. ACSN allows uploading heterogeneous omics data from users on top of the maps for visualization and performing functional analyses. We suggest several scenarios for ACSN application in cancer research, particularly for visualizing high-throughput data, starting from small interfering RNA-based screening results or mutation frequencies to innovative ways of exploring transcriptomes and phosphoproteomes. Integration and analysis of these data in the context of ACSN may help interpret their biological significance and formulate mechanistic hypotheses. ACSN may also support patient stratification, prediction of treatment response and resistance to cancer drugs, as well as design of novel treatment strategies.},
author = {Kuperstein, I. and Bonnet, E. and Nguyen, H. A. and Cohen, D. and Viara, E. and Grieco, L. and Fourquet, S. and Calzone, L. and Russo, C. and Kondratova, M. and Dutreix, M. and Barillot, E. and Zinovyev, A.},
doi = {10.1038/oncsis.2015.19},
file = {:Users/ozlem/Desktop/papers/Disease Map Papers/ACSN.pdf:pdf},
isbn = {21579024 (Electronic)},
issn = {21579024},
journal = {Oncogenesis},
number = {7},
pages = {e160--14},
pmid = {26192618},
publisher = {Nature Publishing Group},
title = {{Atlas of Cancer Signalling Network: A systems biology resource for integrative analysis of cancer data with Google Maps}},
volume = {4},
year = {2015}
}
@article{Carriere2008,
abstract = {Background: The mammalian target of rapamycin (mTOR) is a Ser/Thr kinase that controls cell growth in response to mitogens, as well as amino acid and energy sufficiency. The scaffolding protein Raptor binds to mTOR and recruits substrates to the rapamycin-sensitive mTOR complex 1 (mTORC1). Although Raptor has been shown to be essential for mTORC1 activity, the mechanisms regulating Raptor function remain unknown. Results: Here, we demonstrate that Raptor becomes highly phosphorylated on RXRXXpS/T consensus motifs after activation of the Ras/mitogen-activated protein kinase (MAPK) pathway. Using pharmacological inhibitors and RNA interference, we show that the p90 ribosomal S6 kinases (RSKs) 1 and 2 are required for Raptor phosphorylation in vivo and directly phosphorylate Raptor in vitro. Quantitative mass spectrometry and site-directed mutagenesis revealed that RSK specifically phosphorylates Raptor within an evolutionarily conserved region with no previously known function. Interestingly, expression of oncogenic forms of Ras and MEK that elevate mTORC1 activity induced strong and constitutive phosphorylation of Raptor on these residues. Importantly, we demonstrate that expression of Raptor mutants lacking RSK-dependent phosphorylation sites markedly reduced mTOR phosphotransferase activity, indicating that RSK-mediated phosphorylation of Raptor is important for mTORC1 activation by the Ras/MAPK pathway. Conclusions: We propose a unique mode of mTOR regulation in which RSK-mediated phosphorylation of Raptor regulates mTORC1 activity and thus suggest a means by which the Ras/MAPK pathway might promote rapamycin-sensitive signaling independently of the PI3K/Akt pathway. {\textcopyright} 2008 Elsevier Ltd. All rights reserved.},
author = {Carri{\`{e}}re, Audrey and Cargnello, Marie and Julien, Louis Andr{\'{e}} and Gao, Huanhuan and Bonneil, {\'{E}}ric and Thibault, Pierre and Roux, Philippe P.},
doi = {10.1016/j.cub.2008.07.078},
isbn = {0960-9822 (Print)$\backslash$r0960-9822 (Linking)},
issn = {09609822},
journal = {Current Biology},
keywords = {CELLCYCLE,SIGNALING},
pmid = {18722121},
title = {{Oncogenic MAPK Signaling Stimulates mTORC1 Activity by Promoting RSK-Mediated Raptor Phosphorylation}},
year = {2008}
}
@article{Chardin1993,
abstract = {Nitrification under changing salinities (0-9{\%}), temperatures (6-50??C), ammonia (0-5gNL$\backslash$n                        -1) and nitrite concentrations (0-0.4gNL$\backslash$n                        -1) was investigated in fixed-bed reactors. For all conditions ammonia oxidation rates (AOR) were lower than nitrite oxidation rates (NOR). AORs and NORs increased from 12.5 to 40??C and were very low at 6??C and almost zero at 50??C. No recovery of nitrification was obtained after incubation at 50??C, whereas nitrification was restorable after incubation at 6??C. Ammonia concentrations of 5gNL$\backslash$n                        -1 or nitrite concentrations up to 0.125gNL$\backslash$n                        -1 decreased AOR to almost zero. AORs and NORs recovered if ammonia or nitrite was removed. At concentrations of 1 and 5gNL$\backslash$n                        -1 ammonia AOR and NOR were inhibited by 50{\%}, whereas 27mgN/L nitrite inhibited AOR by 50{\%}. ?? 2011 Elsevier Ltd.},
author = {Chardin, Pierre and Camonis, Jacques H. and Gale, Nicholas W. and {Van Aelst}, Linda and Schlessinger, Joseph and Wigler, Michael H. and Bar-Sagi, Dafna},
doi = {10.1126/science.8493579},
isbn = {09608524 (ISSN)},
issn = {00368075},
journal = {Science},
pmid = {21414774},
title = {{Human Sos1: A guanine nucleotide exchange factor for Ras that binds to GRB2}},
year = {1993}
}
@misc{Kolseth2015,
abstract = {Biotechnology offers extensive possibilities to incorporate new traits into organisms. Genetically modified (GM) traits relevant for agro-ecosystems include traits such as pest resistance and herbicide tolerance in crop plants, increased growth rate in fish and livestock, and enhanced nitrogen-fixation capabilities of soil microbes. In this review, we evaluated the direct and indirect trait-specific effects of GM plants, microbes, and animals on ecosystem processes and found that most of the effects of genetically modified organisms (GMOs) on ecosystem processes are indirect and are the result of associated changes in management strategy rather than a direct effect of the GMOs. Conflicting results on the performance and effects of GMOs are frequently reported, especially regarding crop yield and impacts on soil organisms. This is partly because methods with different levels of resolution have been used in different ecological contexts. Overall, there is little evidence that the effects of GM traits on ecosystem processes act with different mechanisms from those of traits modified using conventional methods. However, little is known about trait-specific effects of GMOs on ecosystem processes even though GMOs have been used for more than three decades. In particular, studies linking genetically modified traits to ecosystem processes at longer time scales are rare, but needed for evaluating trait effects, especially in an evolutionary context. In addition, biotechnology may provide a unique tool for gaining insights into the links between traits and ecosystem processes when integrated into basic ecological research.},
author = {Kolseth, Anna Karin and D'Hertefeldt, Tina and Emmerich, Maren and Forabosco, Flavio and Marklund, Stefan and Cheeke, Tanya E. and Hallin, Sara and Weih, Martin},
booktitle = {Agriculture, Ecosystems and Environment},
doi = {10.1016/j.agee.2015.08.021},
isbn = {0167-8809},
issn = {01678809},
keywords = {Agriculture,Bacillus thuringiensis (Bt),Biotechnology,Ecosystem processes,Ecosystem services,Herbicide-tolerant (HT)},
pages = {96--106},
title = {{Influence of genetically modified organisms on agro-ecosystem processes}},
volume = {214},
year = {2015}
}
@article{Kanehisa2009a,
abstract = {Most human diseases are complex multi-factorial diseases resulting from the combination of various genetic and environmental factors. In the KEGG database resource (http://www.genome.jp/kegg/), diseases are viewed as perturbed states of the molecular system, and drugs as perturbants to the molecular system. Disease information is computerized in two forms: pathway maps and gene/molecule lists. The KEGG PATHWAY database contains pathway maps for the molecular systems in both normal and perturbed states. In the KEGG DISEASE database, each disease is represented by a list of known disease genes, any known environmental factors at the molecular level, diagnostic markers and therapeutic drugs, which may reflect the underlying molecular system. The KEGG DRUG database contains chemical structures and/or chemical components of all drugs in Japan, including crude drugs and TCM (Traditional Chinese Medicine) formulas, and drugs in the USA and Europe. This database also captures knowledge about two types of molecular networks: the interaction network with target molecules, metabolizing enzymes, other drugs, etc. and the chemical structure transformation network in the history of drug development. The new disease/drug information resource named KEGG MEDICUS can be used as a reference knowledge base for computational analysis of molecular networks, especially, by integrating large-scale experimental datasets.},
author = {Kanehisa, Minoru and Goto, Susumu and Furumichi, Miho and Tanabe, Mao and Hirakawa, Mika},
doi = {10.1093/nar/gkp896},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Kanehisa et al. - 2009 - KEGG for representation and analysis of molecular networks involving diseases and drugs(2).pdf:pdf},
isbn = {1362-4962 (Electronic)$\backslash$r0305-1048 (Linking)},
issn = {03051048},
journal = {Nucleic Acids Research},
pmid = {19880382},
title = {{KEGG for representation and analysis of molecular networks involving diseases and drugs}},
year = {2009}
}
@misc{Savi??2016,
abstract = {Targeted nucleases are widely used as tools for genome editing. Two years ago the clustered regularly interspaced short palindromic repeat (CRISPR)-associated Cas9 nuclease was used for the first time, and since then has largely revolutionized the field. The tremendous success of the CRISPR/Cas9 genome editing tool is powered by the ease design principle of the guide RNA that targets Cas9 to the desired DNA locus, and by the high specificity and efficiency of CRISPR/Cas9-generated DNA breaks. Several studies recently used CRISPR/Cas9 to successfully modulate disease-causing alleles in??vivo in animal models and ex??vivo in somatic and induced pluripotent stem cells, raising hope for therapeutic genome editing in the clinics. In this review, we will summarize and discuss such preclinical CRISPR/Cas9 gene therapy reports.},
author = {Savi??, Nata??a and Schwank, Gerald},
booktitle = {Translational Research},
doi = {10.1016/j.trsl.2015.09.008},
isbn = {1878-1810},
issn = {18781810},
pages = {15--21},
pmid = {26470680},
title = {{Advances in therapeutic CRISPR/Cas9 genome editing}},
volume = {168},
year = {2016}
}
@article{Kegg2014,
abstract = {Pathview is a novel tool set that maps, integrates and renders a large variety of biological data on pathways, and produces interpretable graphs with publication quality [1]. Pathview generates both native KEGG view and Graphviz view for pathways. KEGG view keeps all the pathway meta-data, including reaction and signaling contexts important for human reading and interpretation. Graphviz view provides better control of node and edge attributes, better view of pathway topology and analysis statistics.},
author = {Kegg, Example and Graphviz, Example},
doi = {10.1093/bioinformatics/btt285.2},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Kegg, Graphviz - 2014 - Pathview An R package for pathway based data integration and visualization.pdf:pdf},
number = {14},
pages = {8--10},
title = {{Pathview: An R package for pathway based data integration and visualization}},
url = {http://pathview.r-forge.r-project.org/},
volume = {29},
year = {2014}
}
@article{Nakanishi2014,
abstract = {Accumulating evidence has revealed that thePI3K/AKT/PTENpathway acts as a pivotal determinant of cell fate regarding senescence and apoptosis, which is mediated by intracellular reactive oxygen species (ROS) generation. NADPH oxidase (NOX) family of enzymes generates the ROS. The regulation of NOX enzymes is complex, with many members of this family exhibiting complexity in terms of subunit composition, cellular location, and tissue-specific expression. Cells are continuously exposed to the ROS, which represent mutagens and are thought to be a major contributor to several diseases including cancer and aging process. Therefore, cellular ROS sensing and metabolism are firmly regulated by a variety of proteins involved in the redox mechanism. In this review, the roles of oxidative stress in PI3K/AKT/PTEN signaling are summarized with a focus on the links between the pathways and NOX protein in several diseases including cancer and aging.},
author = {Nakanishi, Atsuko and Wada, Yoko and Kitagishi, Yasuko and Matsuda, Satoru},
doi = {10.14336/AD.2014.0500203},
issn = {2152-5250},
journal = {Aging and disease},
month = {jun},
number = {3},
pages = {203--211},
publisher = {JKL International LLC},
title = {{Link between PI3K/AKT/PTEN Pathway and NOX Proteinin Diseases}},
url = {https://www.ncbi.nlm.nih.gov/pubmed/24900943 https://www.ncbi.nlm.nih.gov/pmc/PMC4037312/},
volume = {5},
year = {2014}
}
@article{Waskiewicz1997,
abstract = {Mitogen‐activated protein (MAP) kinases bind tightly to many of their physiologically relevant substrates. We have identified a new subfamily of murine serine/threonine kinases, whose members, MAP kinase‐interacting kinase 1 (Mnk1) and Mnk2, bind tightly to the growth factor‐regulated MAP kinases, Erk1 and Erk2. Mnk1, but not Mnk2, also binds strongly to the stress‐activated kinase, p38. Mnk1 complexes more strongly with inactive than active Erk, implying that Mnk and Erk may dissociate after mitogen stimulation. Erk and p38 phosphorylate Mnk1 and Mnk2, which stimulates their in vitro kinase activity toward a substrate, eukaryotic initiation factor‐4E (eIF‐4E). Initiation factor eIF‐4E is a regulatory phosphoprotein whose phosphorylation is increased by insulin in an Erk‐dependent manner. In vitro, Mnk1 rapidly phosphorylates eIF‐4E at the physiologically relevant site, Ser209. In cells, Mnk1 is post‐translationally modified and enzymatically activated in response to treatment with either peptide growth factors, phorbol esters, anisomycin or UV. Mitogen‐ and stress‐mediated Mnk1 activation is blocked by inhibitors of MAP kinase kinase 1 (Mkk1) and p38, demonstrating that Mnk1 is downstream of multiple MAP kinases. Mnk1 may define a convergence point between the growth factor‐activated and one of the stress‐activated protein kinase cascades and is a candidate to phosphorylate eIF‐4E in cells.},
author = {Waskiewicz, Andrew Jan and Flynn, Andrea and Proud, Christopher G and Cooper, Jonathan A},
doi = {10.1093/emboj/16.8.1909},
journal = {The EMBO Journal},
month = {apr},
number = {8},
pages = {1909 LP  -- 1920},
title = {{Mitogen‐activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2}},
url = {http://emboj.embopress.org/content/16/8/1909.abstract},
volume = {16},
year = {1997}
}
@article{Wu2013,
abstract = {The CRISPR-Cas9 system has been employed to generate mutant alleles in a range of different organisms. However, so far there have not been reports of use of this system for efficient correction of a genetic disease. Here we show that mice with a dominant mutation in Crygc gene that causes cataracts could be rescued by coinjection into zygotes of Cas9 mRNA and a single-guide RNA (sgRNA) targeting the mutant allele. Correction occurred via homology-directed repair (HDR) based on an exogenously supplied oligonucleotide or the endogenous WT allele, with only rare evidence of off-target modifications. The resulting mice were fertile and able to transmit the corrected allele to their progeny. Thus, our study provides proof of principle for use of the CRISPR-Cas9 system to correct genetic disease.},
author = {Wu, Yuxuan and Liang, Dan and Wang, Yinghua and Bai, Meizhu and Tang, Wei and Bao, Shiming and Yan, Zhiqiang and Li, Dangsheng and Li, Jinsong},
doi = {10.1016/j.stem.2013.10.016},
issn = {1875-9777},
journal = {Cell stem cell},
number = {6},
pages = {659--662},
pmid = {24315440},
title = {{Correction of a Genetic Disease in Mouse via Use of CRISPR-Cas9.pdf.crdownload}},
url = {http://www.ncbi.nlm.nih.gov/pubmed/24315440},
volume = {13},
year = {2013}
}
@article{Ingalls2012,
abstract = {Systems techniques are integral to current research in molecular cell biology. These systems ap- proaches stand in contrast to the historically reductionist paradigm of molecular biology. The shift toward a systems perspective was gradual; it passed a turning point at the end of the 20th cen- tury, when newly developed experimental techniques provided system-level observations of cellular networks. These observations revealed the full complexity of these networks, and made it clear that traditional (largely qualitative) molecular biology techniques are ill-equipped for the investi- gation of these systems, which often exhibit non-intuitive behaviour. This point was illustrated in a thought experiment proposed by Yuri Lazebnik (Lazebnik, 2002). He described a (failed) attempt to reverse-engineer a transistor radio using qualitative methods analogous to those used in tradi- tional molecular biology. Lazebnik's exercise demonstrates that without a quantitative framework to describe large networks of interacting components, the functioning of cellular networks cannot be resolved. A quantitative approach to molecular biology allows traditional interaction diagrams to be extended to mechanistic mathematical models. These models serve as working hypotheses: they help us to understand and predict the behaviour of complex systems. The application of mathematical modelling to molecular cell biology is not a new endeavour; there is a long history of mathematical descriptions of biochemical and genetic networks. Successful applications include Alan Turing's description of patterning in development (discussed by Murray, 2003), the models of neuronal signalling developed by Alan Hodgkin and Andrew Huxley (reviewed by Rinzel, 1990), and Denis Noble's mechanistic modelling of the heart (Noble, 2004). Despite these successes, this sort of mathematical work has not been considered central to (most of) molecular cell biology. That attitude is changing; system-level investigations are now frequently accompanied by mathematical models, and such models may soon become requisites for describing the behaviour of cellular networks.},
author = {Ingalls, Bp},
doi = {0262018888},
isbn = {9780262018883},
issn = {03043894},
journal = {Mathematical Modelling in Systems Biology : An Introduction},
pmid = {17606325},
title = {{Mathematical Modeling in Systems Biology: An Introduction}},
year = {2012}
}
@article{Seiter2005,
abstract = {Topoisomerase II inhibitors represent a broad class of antineoplastic agents with a wide spectrum of activity against malignancies. Topoisomerase II inhibitors include the anthracyclines, mitoxantrone and epipodophyllotoxins. Short-term toxicity includes myelosuppression and gastrointestinal toxicity. Long-term survivors are at risk of cardiac toxicity and secondary leukaemia. This article discusses these toxicities in detail, including administration of these agents to patients with hepatic and/or renal insufficiency, and the need for dose adjustments in selected patient populations.},
author = {Seiter, Karen},
doi = {10.1517/14740338.4.2.219},
isbn = {1474-0338},
issn = {1474-0338},
journal = {Expert Opinion on Drug Safety},
number = {2},
pages = {219--234},
pmid = {15794715},
title = {{Toxicity of the topoisomerase II inhibitors}},
url = {http://www.tandfonline.com/doi/full/10.1517/14740338.4.2.219},
volume = {4},
year = {2005}
}
@article{Hirschman2012,
abstract = {Molecular biology has become heavily dependent on biological knowledge encoded in expert curated biological databases. As the volume of biological literature increases, biocurators need help in keeping up with the literature; (semi-) automated aids for biocuration would seem to be an ideal application for natural language processing and text mining. However, to date, there have been few documented successes for improving biocuration throughput using text mining. Our initial investigations took place for the workshop on 'Text Mining for the BioCuration Workflow' at the third International Biocuration Conference (Berlin, 2009). We interviewed biocurators to obtain workflows from eight biological databases. This initial study revealed high-level commonalities, including (i) selection of documents for curation; (ii) indexing of documents with biologically relevant entities (e.g. genes); and (iii) detailed curation of specific relations (e.g. interactions); however, the detailed workflows also showed many variabilities. Following the workshop, we conducted a survey of biocurators. The survey identified biocurator priorities, including the handling of full text indexed with biological entities and support for the identification and prioritization of documents for curation. It also indicated that two-thirds of the biocuration teams had experimented with text mining and almost half were using text mining at that time. Analysis of our interviews and survey provide a set of requirements for the integration of text mining into the biocuration workflow. These can guide the identification of common needs across curated databases and encourage joint experimentation involving biocurators, text mining developers and the larger biomedical research community.},
author = {Hirschman, Lynette and Burns, Gully A.P.C. and Krallinger, Martin and Arighi, Cecilia and Cohen, K. Bretonnel and Valencia, Alfonso and Wu, Cathy H. and Chatr-Aryamontri, Andrew and Dowell, Karen G. and Huala, Eva and Louren{\c{c}}o, An{\'{a}}lia and Nash, Robert and Veuthey, Anne Lise and Wiegers, Thomas and Winter, Andrew G.},
doi = {10.1093/database/bas020},
file = {:Users/ozlem/Documents/text mining papers to read/bas020.pdf:pdf},
isbn = {1758-0463 (Electronic)},
issn = {17580463},
journal = {Database},
number = {June},
pages = {1--10},
pmid = {22513129},
title = {{Text mining for the biocuration workflow}},
volume = {2012},
year = {2012}
}
@article{Saez-Rodriguez2008b,
abstract = {MOTIVATION Linking experimental data to mathematical models in biology is impeded by the lack of suitable software to manage and transform data. Model calibration would be facilitated and models would increase in value were it possible to preserve links to training data along with a record of all normalization, scaling, and fusion routines used to assemble the training data from primary results. RESULTS We describe the implementation of DataRail, an open source MATLAB-based toolbox that stores experimental data in flexible multi-dimensional arrays, transforms arrays so as to maximize information content, and then constructs models using internal or external tools. Data integrity is maintained via a containment hierarchy for arrays, imposition of a metadata standard based on a newly proposed MIDAS format, assignment of semantically typed universal identifiers, and implementation of a procedure for storing the history of all transformations with the array. We illustrate the utility of DataRail by processing a newly collected set of approximately 22 000 measurements of protein activities obtained from cytokine-stimulated primary and transformed human liver cells. AVAILABILITY DataRail is distributed under the GNU General Public License and available at http://code.google.com/p/sbpipeline/},
author = {Saez-Rodriguez, Julio and Goldsipe, Arthur and Muhlich, Jeremy and Alexopoulos, Leonidas G. and Millard, Bjorn and Lauffenburger, Douglas A. and Sorger, Peter K.},
doi = {10.1093/bioinformatics/btn018},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Saez-Rodriguez et al. - 2008 - Flexible informatics for linking experimental data to mathematical models via DataRail.pdf:pdf},
isbn = {1460-2059 (Electronic)},
issn = {13674803},
journal = {Bioinformatics},
number = {6},
pages = {840--847},
pmid = {18218655},
title = {{Flexible informatics for linking experimental data to mathematical models via DataRail}},
volume = {24},
year = {2008}
}
@article{Lourenco2016,
abstract = {Direct measurement of glucose in the brain extracellular space with high spatial and temporal resolution is needed for understanding of brain energy metabolism. In this work we developed and extensively characterized an amperometric glucose microbiosensor using ceramic-based platinum multisite microelectrode arrays (MEAs) for measuring extracellular glucose in the rat brain in vivo. Glucose-oxidase (GOx) was immobilized at the microelectrode surface by cross-linking with glutaraldehyde in the presence of BSA. The in vitro evaluations supported the high analytical performance of these microbiosensors for application in the brain, including high selectivity and sensitivity, adequate linear range and limit of detection, good operational stability and response time, minimal oxygen-, pH- and temperature-dependencies. The microbiosensors were successfully used for measurements of glucose with high temporal and spatial resolution in the hippocampus of anesthetized rats in response to systemic, local glucose changes and upon glutamatergic stimulation. Overall, the results support the suitability of these microbiosensors for measuring rapid changes of extracellular glucose in the rat brain.},
author = {Louren{\c{c}}o, C{\'{a}}tia F. and Ledo, Ana and Laranjinha, Jo{\~{a}}o and Gerhardt, Greg A. and Barbosa, Rui M.},
doi = {10.1016/j.snb.2016.06.083},
isbn = {0925-4005},
issn = {09254005},
journal = {Sensors and Actuators, B: Chemical},
keywords = {Brain in vivo,Glucose measurement,Glucose oxidase,Microbiosensor,Microelectrode arrays},
pages = {298--307},
title = {{Microelectrode array biosensor for high-resolution measurements of extracellular glucose in the brain}},
volume = {237},
year = {2016}
}
@article{Mason2014a,
abstract = {RAD51 is the central protein that catalyzes DNA repair via homologous recombination (HR), a process that ensures genomic stability. RAD51 protein is commonly expressed at high levels in cancer cells relative to their non-cancerous precursors. High levels of RAD51 expression can lead to the formation of genotoxic RAD51 protein complexes on undamaged chromatin. We developed a therapeutic approach that exploits this potentially toxic feature of malignancy, using compounds that stimulate the DNA binding activity of RAD51 to promote cancer cell death. A panel of immortalized cell lines was challenged with the RAD51-stimulatory compound RS-1. Resistance to RS-1 tended to occur in cells with higher levels of RAD54L and RAD54B, which are Swi2/Snf2-related translocases known to dissociate RAD51 filaments from double-stranded DNA. In PC3 prostate cancer cells, RS-1 induced lethality was accompanied by the formation of microscopically visible RAD51 nuclear protein foci occurring in the absence of any DNA-damaging treatment. Treatment with RS-1 promoted significant anti-tumor responses in a mouse model, providing proof of principle for this novel therapeutic strategy.},
author = {Mason, Jennifer M. and Logan, Hillary L. and Budke, Brian and Wu, Megan and Pawlowski, Michal and Weichselbaum, Ralph R. and Kozikowski, Alan P. and Bishop, Douglas K. and Connell, Philip P.},
doi = {10.1158/0008-5472.CAN-13-3220},
isbn = {7738348119},
issn = {15387445},
journal = {Cancer Research},
number = {13},
pages = {3546--3555},
pmid = {24753542},
title = {{The rad51-stimulatory compound rs-1 can exploit the rad51 overexpression that exists in cancer cells and tumors}},
volume = {74},
year = {2014}
}
@article{Tong2004a,
abstract = {... Thus, the complete genetic  network will represent a global  map of functional relationships between genes. ... effects we see within a dense local neighborhood of the yeast  genetic  interaction  map (Fig. ...  Mapping the expected dense network of digenic interactions in humans will be ...},
author = {Tong, A H Y},
doi = {10.1126/science.1091317},
journal = {Science (New York, NY)},
number = {5659},
pages = {808--813},
title = {{Global Mapping of the Yeast Genetic Interaction Network}},
volume = {303},
year = {2004}
}
@article{Albert2002,
abstract = {Complex networks describe a wide range of systems in nature and society. Frequently cited examples include the cell, a network of chemicals linked by chemical reactions, and the Internet, a network of routers and computers connected by physical links. While traditionally these systems have been modeled as random graphs, it is increasingly recognized that the topology and evolution of real networks are governed by robust organizing principles. This article reviews the recent advances in the field of complex networks, focusing on the statistical mechanics of network topology and dynamics. After reviewing the empirical data that motivated the recent interest in networks, the authors discuss the main models and analytical tools, covering random graphs, small-world and scale-free networks, the emerging theory of evolving networks, and the interplay between topology and the network's robustness against failures and attacks.},
author = {Albert, R and Barabasi, A L},
doi = {10.1103/RevModPhys.74.47},
issn = {0034-6861},
journal = {Rev. Mod. Phys.},
keywords = {Biblioscape,Complexity,Mathematics,Network,Review,Statistics,art. no. 025101,evolving networks,growing random networks,highly optimized tolerance,mean-field theory,random graphs,scale-free networks,scientific collaboration networks,small-world networks,wide-web,胡明},
pmid = {174548700003},
title = {{Statistical mechanics of complex networks}},
year = {2002}
}
@misc{LeCurieux-Belfond2009,
abstract = {Many genetically modified plants have been developed, and four of them (soya, maize, cotton, and colza) representing more than 99{\%} of commercial crops, are widely distributed, mainly in the United States and in America [ISAAA, 2006. Report on global status on biotech/GM crops, Brief 35. International Service for the Acquisition of Agri-biotech Applications organization, US]. Yet all over the world policy is still in development in regard to authorization of modified plants and modified and/or cloned animals for food or feed and for their environmental release. The most advanced animal commercial projects concern various fish species, more easy to genetically transform, notably because conception and development take place in water and easy access to numerous eggs. A request for authorization to introduce genetically modified (GM) salmon onto the market has been presented to the Food and Drug Administration (FDA) of the US. In the interim, questions have been raised concerning the impacts of transgenic salmon, modified for productivity, on aquaculture, wildlife, ecosystems and on human health. Herein we review these scientific studies and sanitary, environmental, social and economic arguments. This paper analyses current gaps in the knowledge of the impacts of transgenic fish and proposes legislation orientations necessary for environmental and sanitary protection, should the marketing of animal genetically modified organisms (GMOs) be authorized. {\textcopyright} 2008 Elsevier Ltd. All rights reserved.},
author = {{Le Curieux-Belfond}, Olivier and Vandelac, Louise and Caron, Joseph and S{\'{e}}ralini, Gilles {\'{E}}ric},
booktitle = {Environmental Science and Policy},
doi = {10.1016/j.envsci.2008.10.001},
isbn = {14629011},
issn = {14629011},
keywords = {Aquaculture policy,Environmental protection,Food safety,Genetically modified organisms (GMOs),Transgenic salmon},
number = {2},
pages = {170--189},
title = {{Factors to consider before production and commercialization of aquatic genetically modified organisms: the case of transgenic salmon}},
volume = {12},
year = {2009}
}
@article{Olayioye1998,
abstract = {{\textless}p{\textgreater}The different epidermal growth factor (EGF)-related peptides elicit a diverse array of biological responses as the result of their ability to activate distinct subsets of ErbB receptor dimers, leading to the recruitment of different intracellular signaling networks. To specifically examine dimerization-dependent modulation of receptor signaling, we constructed NIH 3T3 cell lines expressing ErbB-1 and ErbB-2 singly and in pairwise combinations with each other ErbB family member. This model system allowed the comparison of EGF-activated ErbB-1 with ErbB-1 activated by Neu differentiation factor (NDF)-induced heterodimerization with ErbB-4. In both cases, ErbB-1 coupled to the adaptor protein Shc, but only when activated by EGF was it able to interact with Grb2. Compared to the rapid internalization of EGF-activated ErbB-1, NDF-activated ErbB-1 showed delayed internalization characteristics. Furthermore, the p85 subunit of phosphatidylinositol kinase (PI3-K) associated with EGF-activated ErbB-1 in a biphasic manner, whereas association with ErbB-1 transactivated by ErbB-4 was monophasic. The signaling properties of ErbB-2 following heterodimerization with the other ErbB receptors or homodimerization induced by point mutation or monoclonal antibody treatment were also analyzed. ErbB-2 binding to peptides containing the Src homology 2 domain of Grb2 or p85 and the phosphotyrosine binding domain of Shc varied according to the mode of receptor activation. Finally, tryptic phosphopeptide mapping of both ErbB-1 and ErbB-2 revealed that receptor phosphorylation is dependent on the dimerization partner. Differential receptor phosphorylation may, therefore, be the basis for the differences in the signaling properties observed.{\textless}/p{\textgreater}},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Olayioye, Monilola A. and Graus-Porta, Diana and Beerli, Roger R. and Rohrer, Jack and Gay, Brigitte and Hynes, Nancy E.},
doi = {10.1128/MCB.18.9.5042},
eprint = {NIHMS150003},
isbn = {0270-7306 (Print)$\backslash$r0270-7306 (Linking)},
issn = {0270-7306},
journal = {Molecular and Cellular Biology},
pmid = {9710588},
title = {{ErbB-1 and ErbB-2 Acquire Distinct Signaling Properties Dependent upon Their Dimerization Partner}},
year = {1998}
}
@article{Hoehndorf2011a,
abstract = {BACKGROUND:Systems biology is an approach to biology that emphasizes the structure and dynamic behavior of biological systems and the interactions that occur within them. To succeed, systems biology crucially depends on the accessibility and integration of data across domains and levels of granularity. Biomedical ontologies were developed to facilitate such an integration of data and are often used to annotate biosimulation models in systems biology.RESULTS:We provide a framework to integrate representations of in silico systems biology with those of in vivo biology as described by biomedical ontologies and demonstrate this framework using the Systems Biology Markup Language. We developed the SBML Harvester software that automatically converts annotated SBML models into OWL and we apply our software to those biosimulation models that are contained in the BioModels Database. We utilize the resulting knowledge base for complex biological queries that can bridge levels of granularity, verify models based on the biological phenomenon they represent and provide a means to establish a basic qualitative layer on which to express the semantics of biosimulation models.CONCLUSIONS:We establish an information flow between biomedical ontologies and biosimulation models and we demonstrate that the integration of annotated biosimulation models and biomedical ontologies enables the verification of models as well as expressive queries. Establishing a bi-directional information flow between systems biology and biomedical ontologies has the potential to enable large-scale analyses of biological systems that span levels of granularity from molecules to organisms.},
author = {Hoehndorf, Robert and Dumontier, Michel and Gennari, John H. and Wimalaratne, Sarala and de Bono, Bernard and Cook, Daniel L. and Gkoutos, Georgios V.},
doi = {10.1186/1752-0509-5-124},
isbn = {1752-0509},
issn = {17520509},
journal = {BMC Systems Biology},
pmid = {21835028},
title = {{Integrating systems biology models and biomedical ontologies}},
year = {2011}
}
@article{Hallberg1994,
abstract = {It has recently been shown that Ras proteins interact directly with Raf serine/threonine kinases in vitro and in the yeast two-hybrid system, leading to speculation that Raf proteins function as effectors for Ras. Here it is demonstrated that the endogenous Raf-1 protein co-immunoprecipitates with Ras from mammalian cells when the non-neutralizing anti-Ras monoclonal antibody Y13-238 is used. The formation of a Ras-Raf complex is absolutely dependent on prior treatment of the cells with a stimulus that activates Ras: phorbol ester or anti-T cell receptor antibody in the case of human peripheral blood T lymphoblasts, or epidermal growth factor in the case of Rat-1 fibroblasts. Up to 3{\%} of cellular Raf-1 can be found in association with Ras. The association is not competed by addition of exogenous GST-Raf to the cell lysates and is therefore unlikely to be due to Ras-Raf binding after cell lysis. Specific interaction of Ras and Raf therefore occurs in intact mammalian cells in response to stimuli that cause Ras to become GTP-bound.},
author = {Hallberg, Bengt and Rayter, Sydonia I. and Downward, Julian},
isbn = {0021-9258 (Print)},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {8307946},
title = {{Interaction of Ras and Raf in intact mammalian cells upon extracellular stimulation}},
year = {1994}
}
@article{Calzone2008a,
abstract = {We present, here, a detailed and curated map of molecular interactions taking place in the regulation of the cell cycle by the retinoblastoma protein (RB/RB1). Deregulations and/or mutations in this pathway are observed in most human cancers. The map was created using Systems Biology Graphical Notation language with the help of CellDesigner 3.5 software and converted into BioPAX 2.0 pathway description format. In the current state the map contains 78 proteins, 176 genes, 99 protein complexes, 208 distinct chemical species and 165 chemical reactions. Overall, the map recapitulates biological facts from approximately 350 publications annotated in the diagram. The network contains more details about RB/E2F interaction network than existing large-scale pathway databases. Structural analysis of the interaction network revealed a modular organization of the network, which was used to elaborate a more summarized, higher-level representation of RB/E2F network. The simplification of complex networks opens the road for creating realistic computational models of this regulatory pathway.},
author = {Calzone, Laurence and Gelay, Am{\'{e}}lie and Zinovyev, Andrei and Radvanyi, Fran{\c{c}}ois and Barillot, Emmanuel},
doi = {10.1038/msb.2008.7},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Calzone et al. - 2008 - A comprehensive modular map of molecular interactions in RBE2F pathway.pdf:pdf},
isbn = {1744-4292},
issn = {1744-4292},
journal = {Molecular Systems Biology},
keywords = {cell-cycle regulation,e2f,rb pathway,rb1,systems-},
number = {173},
pages = {1--12},
pmid = {18319725},
title = {{A comprehensive modular map of molecular interactions in RB/E2F pathway}},
url = {http://msb.embopress.org/cgi/doi/10.1038/msb.2008.7},
volume = {4},
year = {2008}
}
@article{FatihKOCABAS1*2016,
author = {{Fatih KOCABAŞ1,*}, Enes Kemal ERGİN2},
journal = {Turkish Journal of Biology},
pages = {239--249},
title = {{Identification of small molecule binding pocket for inhibition of Crimean–Congo hemorrhagic fever virus OTU protease}},
volume = {40},
year = {2016}
}
@article{Jackman2010,
abstract = {Gigabase-scale genome assemblies are now feasible using short-read sequencing technology, bringing the cost of such projects below the million-dollar mark.},
author = {Jackman, Shaun D and Birol, İnan{\c{c}}},
doi = {10.1186/gb-2010-11-1-202},
isbn = {1465-6914 (Electronic)$\backslash$r1465-6906 (Linking)},
issn = {1465-6906},
journal = {Genome Biology},
number = {1},
pages = {202},
pmid = {20128932},
title = {{Assembling genomes using short-read sequencing technology}},
url = {http://genomebiology.biomedcentral.com/articles/10.1186/gb-2010-11-1-202},
volume = {11},
year = {2010}
}
@article{Nishimasu2014,
abstract = {The CRISPR-associated endonuclease Cas9 can be targeted to specific genomic loci by single guide RNAs (sgRNAs). Here, we report the crystal structure of Streptococcus pyogenes Cas9 in complex with sgRNA and its target DNA at 2.5 {\AA} resolution. The structure revealed a bilobed architecture composed of target recognition and nuclease lobes, accommodating the sgRNA:DNA heteroduplex in a positively charged groove at their interface. Whereas the recognition lobe is essential for binding sgRNA and DNA, the nuclease lobe contains the HNH and RuvC nuclease domains, which are properly positioned for cleavage of the complementary and noncomplementary strands of the target DNA, respectively. The nuclease lobe also contains a carboxyl-terminal domain responsible for the interaction with the protospacer adjacent motif (PAM). This high-resolution structure and accompanying functional analyses have revealed the molecular mechanism of RNA-guided DNA targeting by Cas9, thus paving the way for the rational design of new, versatile genome-editing technologies. {\textcopyright} 2014 Elsevier Inc.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Nishimasu, Hiroshi and Ran, F. Ann and Hsu, Patrick D. and Konermann, Silvana and Shehata, Soraya I. and Dohmae, Naoshi and Ishitani, Ryuichiro and Zhang, Feng and Nureki, Osamu},
doi = {10.1016/j.cell.2014.02.001},
eprint = {NIHMS150003},
isbn = {1097-4172 (Electronic)$\backslash$n0092-8674 (Linking)},
issn = {00928674},
journal = {Cell},
number = {5},
pages = {935--949},
pmid = {24529477},
title = {{Crystal structure of Cas9 in complex with guide RNA and target DNA}},
volume = {156},
year = {2014}
}
@article{Merico2009a,
abstract = {Networks in biology can appear complex and difficult to decipher. We illustrate how to interpret biological networks with the help of frequently used visualization and analysis patterns.},
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Merico, Daniele and Gfeller, David and Bader, Gary D.},
doi = {10.1038/nbt.1567},
eprint = {NIHMS150003},
file = {:Users/ozlem/Dropbox/papers/Biological Networks/nbt.1567.pdf:pdf},
isbn = {1546-1696 (Electronic)$\backslash$r1087-0156 (Linking)},
issn = {10870156},
journal = {Nature Biotechnology},
number = {10},
pages = {921--924},
pmid = {19816451},
publisher = {Nature Publishing Group},
title = {{How to visually interpret biological data using networks}},
url = {http://dx.doi.org/10.1038/nbt.1567},
volume = {27},
year = {2009}
}
@article{Cevik2016,
abstract = {{\textcopyright} 2016 Elsevier B.V. In this study, an immunosensor was designed to utilize for the detection of prostate specific antigen (PSA) based on three different generations (G1, G2 and G3) of ferrocene (Fc) cored polyamidiamine dendrimers (Fc-PAMAM) gold (Au) electrode. The self-assembled monolayer principle (SAM) was used to fabricate the sensitive, selective and disposable immunosensor electrodes. In electrode fabrication cysteamine (Cys) was the first agent covalently linked on the Au electrode surface. Immobilized redox center (ferrocene) cored PAMAM dendrimers served as a layer for the further binding of biological components. The monoclonal antibody of PSA (anti-PSA) was covalently immobilized on dendrimers which were attached onto the modified Au surface (Au/Cys/Fc-PAMAMs/anti-PSA). PSA levels were quantitatively analyzed by using electrochemical differential pulse voltammetry (DPV) whose lowest detection limit was calculated as 0.001 ng mL−1. The Au/Cys/FcPAMAM/anti-PSA immunosensor showed excellent performance for PSA at the pulse amplitude; 50 mV and the scan rate; 10 mV/s in a wide linear concentration range of 0.01 ng–100 ng mL−1. Analytical performance and specificity assays were carried out using human serum and different proteins.},
author = {{\c{C}}evik, E. and Bahar, {\"{O}}. and Şenel, M. and Abasıyanık, M.F.},
doi = {10.1016/j.bios.2016.07.064},
issn = {18734235},
journal = {Biosensors and Bioelectronics},
keywords = {Dendrimer,Ferrocene,Immunosensor,Prostate specific antigen},
title = {{Construction of novel electrochemical immunosensor for detection of prostate specific antigen using ferrocene-PAMAM dendrimers}},
volume = {86},
year = {2016}
}
@article{Saez-Rodriguez2007,
abstract = {Cellular decisions are determined by complex molecular interaction networks. Large-scale signaling networks are currently being reconstructed, but the kinetic parameters and quantitative data that would allow for dynamic modeling are still scarce. Therefore, computational studies based upon the structure of these networks are of great interest. Here, a methodology relying on a logical formalism is applied to the functional analysis of the complex signaling network governing the activation of T cells via the T cell receptor, the CD4/CD8 co-receptors, and the accessory signaling receptor CD28. Our large-scale Boolean model, which comprises 94 nodes and 123 interactions and is based upon well-established qualitative knowledge from primary T cells, reveals important structural features (e.g., feedback loops and network-wide dependencies) and recapitulates the global behavior of this network for an array of published data on T cell activation in wild-type and knock-out conditions. More importantly, the model predicted unexpected signaling events after antibody-mediated perturbation of CD28 and after genetic knockout of the kinase Fyn that were subsequently experimentally validated. Finally, we show that the logical model reveals key elements and potential failure modes in network functioning and provides candidates for missing links. In summary, our large-scale logical model for T cell activation proved to be a promising in silico tool, and it inspires immunologists to ask new questions. We think that it holds valuable potential in foreseeing the effects of drugs and network modifications.},
author = {Saez-Rodriguez, Julio and Simeoni, Luca and Lindquist, Jonathan A. and Hemenway, Rebecca and Bommhardt, Ursula and Arndt, Boerge and Haus, Utz Uwe and Weismantel, Robert and Gilles, Ernst D. and Klamt, Steffen and Schraven, Burkhart},
doi = {10.1371/journal.pcbi.0030163},
file = {:Users/ozlem/Desktop/papers/Disease Map Papers/journal.pcbi.0030163.PDF:PDF},
isbn = {1553-7358 (Electronic)$\backslash$n1553-734X (Linking)},
issn = {1553734X},
journal = {PLoS Computational Biology},
number = {8},
pages = {1580--1590},
pmid = {17722974},
title = {{A logical model provides insights into T cell receptor signaling}},
volume = {3},
year = {2007}
}
@article{Also2018,
author = {Also, See},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Also - 2018 - KEGG.db.pdf:pdf},
title = {{KEGG.db}},
year = {2018}
}
@inproceedings{Hascup2013,
abstract = {A major goal of our research is to develop an implantable device for routine amperometric recordings of l-glutamate and other neurotransmitters in the mammalian central nervous system. Specifically, we wanted to develop a microelectrode that is (1) mass produced such that other laboratories can easily utilize the same recording technology, (2) designed to study multiple brain regions and neurotransmitters in various in vitro and in vivo systems, and (3) configured for “self-referencing” recordings, which allows for measurements of resting or tonic levels of neurotransmitters, cross-checking of the selectivity of the microelectrode measures, and improved signal-to-noise ratio by noise subtraction. The present chapter documents our current capabilities of measuring l-glutamate and several other neurotransmitters with rapid temporal resolution using mass-fabricated microelectrode arrays formed on ceramic. We have routinely demonstrated that these electrodes have fast temporal resolution ({\textless}1 s), excellent spatial resolution (microns), and low detection limits (≤200 nM) and cause minimal damage (50–100 $\mu$m) to surrounding brain tissue. While not a comprehensive assessment of the technology, this chapter contains a large amount of information regarding the fabrication, use, and potential pitfalls of this technology.},
author = {Hascup, Kevin N. and Hascup, Erin R. and Littrell, O. Meagan and Hinzman, Jason M. and Werner, Catherine E. and Davis, Verda A. and Burmeister, Jason J. and Pomerleau, Francois and Quintero, Jorge E. and Huettl, Peter and Gerhardt, Greg A.},
booktitle = {Neuromethods},
doi = {10.1007/978-1-62703-370-1-2},
isbn = {9781627033695},
issn = {08932336},
keywords = {Amperometry,Biosensor,Glutamate,In vivo electrochemistry,Microelectrode array,Neurotransmission,Photolithography},
pages = {27--54},
title = {{Microelectrode array fabrication and optimization for selective neurochemical detection}},
volume = {80},
year = {2013}
}
@misc{Boone2007,
abstract = {The development and application of genetic tools and resources has enabled a partial genetic-interaction network for the yeast Saccharomyces cerevisiae to be compiled. Analysis of the network, which is ongoing, has already provided a clear picture of the nature and scale of the genetic interactions that robustly sustain biological systems, and how cellular buffering is achieved at the molecular level. Recent studies in yeast have begun to define general principles of genetic networks, and also pave the way for similar studies in metazoan model systems. A comparative understanding of genetic-interaction networks promises insights into some long-standing genetic problems, such as the nature of quantitative traits and the basis of complex inherited disease.},
archivePrefix = {arXiv},
arxivId = {arXiv:1011.1669v3},
author = {Boone, Charles and Bussey, Howard and Andrews, Brenda J.},
booktitle = {Nature Reviews Genetics},
doi = {10.1038/nrg2085},
eprint = {arXiv:1011.1669v3},
isbn = {1471-0056 (Print)$\backslash$n1471-0056 (Linking)},
issn = {14710056},
number = {6},
pages = {437--449},
pmid = {17510664},
title = {{Exploring genetic interactions and networks with yeast}},
volume = {8},
year = {2007}
}
@article{Elenius1999,
abstract = {Receptor tyrosine kinases regulate cell behavior by activating specific signal transduction cascades. Epidermal growth factor (EGF) receptor tyrosine kinases include ErbB1, ErbB2, ErbB3 and ErbB4. ErbB4 is a tyrosine kinase receptor that binds neuregulins (NRG) and several other EGF family members. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis identified two isoforms of ErbB4 that differed in their cytoplasmic domain sequences. Specifically, RT-PCR using primers flanking the putative phosphatidyl inositol 3-kinase (PI3-K) binding site of ErbB4 generated two specific bands when human and mouse heart and kidney tissues were analysed. Cloning and sequencing of these RT-PCR products revealed that one of the ErbB4 isoforms (ErbB4 CYT-2) lacked a 16 amino acid sequence including a putative PI3-K binding site, that was present in the other isoform (ErbB4 CYT-1). RT-PCR analysis of mouse tissues suggested that the expression of ErbB4 CYT-1 and ErbB4 CYT-2 was tissue-specific. Heart, breast and abdominal aorta expressed predominantly ErbB4 CYT-1 whereas neural tissues and kidney expressed predominantly ErbB4 CYT-2. To ascertain whether the absence of the putative PI3-K binding site in ErbB4 CYT-2 also resulted in the loss of PI3-K activity, NIH3T3 cell lines overexpressing ErbB4 CYT-1 or ErbB4 CYT-2 were produced. NRG-1 bound to and stimulated equivalent tyrosine phosphorylation of both isoforms. However, unlike ErbB4 CYT-1, the ErbB4 CYT-2 isoform was unable to bind the p85 subunit of PI3-K and to stimulate PI3-K activity in these cells. Furthermore, tyrosine phosphorylation of p85 or association of PI3-K activity with phosphotyrosine was not induced in NRG-1 treated cells expressing ErbB4 CYT-2, indicating that this isoform was incapable of activating PI3-K even indirectly. It was concluded that a novel naturally occurring ErbB4 isoform exists with a deletion of the cytoplasmic domain sequence required for the activation of the PI3-K intracellular signal transduction pathway and that this is the only PI3-K binding site in ErbB4.},
author = {Elenius, Klaus and Choi, Caroline J. and Paul, Subroto and Santiestevan, Eric and Nishi, Eiichiro and Klagsbrun, Michael},
doi = {10.1038/sj.onc.1202612},
isbn = {0950-9232},
issn = {09509232},
journal = {Oncogene},
keywords = {Alternative splicing,Chemotaxis,EGF receptor,Survival},
pmid = {10353604},
title = {{Characterization of a naturally occurring ErbB4 isoform that does not bind or activate phosphatidyl inositol 3-kinase}},
year = {1999}
}
@article{Wang1998b,
abstract = {Interleukin 3-dependent murine 32D cells do not detectably express members of the ErbB receptor family and do not proliferate in response to known ligands for these receptors. 32D transfectants were generated expressing human ErbB4 alone (32D.E4) or with ErbB2 (32D.E2/E4). Epidermal growth factor (EGF), neuregulin 1-beta (NRG1-beta), betacellulin (BTC), transforming growth factor-alpha (TGF-alpha), heparin binding-EGF (HB-EGF), and amphiregulin were analyzed for their ability to mediate mitogenesis in these transfectants. 32D.E4 responded mitogenically to NRG1-beta and BTC. Surprisingly, EGF also induced significant DNA synthesis and TGF-alpha was negligibly mitogenic on 32D.E4 cells, whereas HB-EGF and amphiregulin were inactive. Although coexpression of ErbB2 with ErbB4 in 32D.E2/E4 cells did not significantly alter DNA synthesis in response to NRG1-beta or BTC, it greatly enhanced mitogenesis elicited by EGF and TGF-alpha and unmasked the ability of HB-EGF to induce proliferation. EGF-related ligands that exhibited potent mitogenic activity on 32D.E2/E4 cells at low concentrations induced adherence, morphological alterations, and up-regulation of the Mac-1 integrin and FcgammaRII/III at higher concentrations. While 125I-EGF could be specifically crosslinked to both 32D.E4 and 32D.E2/E4 cells, its crosslinking capacity was greatly enhanced in the cotransfected cells. The ability of the various ligands to mediate proliferation and/or adhesion in the two transfectants correlated with their capacity to induce substrate tyrosine phosphorylation and to initiate and sustain activation of mitogen-activated protein kinase. We conclude that the ability of ErbB4 to mediate signal transduction through EGF-like ligands is broader than previously assumed and can be profoundly altered by the concomitant expression of ErbB2.},
author = {Wang, L.-M. and Kuo, A. and Alimandi, M. and Veri, M. C. and Lee, C.-C. and Kapoor, V. and Ellmore, N. and Chen, X.-H. and Pierce, J. H.},
doi = {10.1073/pnas.95.12.6809},
isbn = {0027-8424 (Print)$\backslash$r0027-8424 (Linking)},
issn = {0027-8424},
journal = {Proceedings of the National Academy of Sciences},
pmid = {9618494},
title = {{ErbB2 expression increases the spectrum and potency of ligand-mediated signal transduction through ErbB4}},
year = {1998}
}
@article{Tsujino2000,
abstract = {Activating transcription factor 3 (ATF3), a member of ATF/CREB family of transcription factors, is induced in a variety of stressed tissue. ATF3 regulates transcription by binding to DNA sites as a homodimer or heterodimer with Jun proteins. The purpose of this study was to examine the expression and regulation of ATF3 after axonal injury in neurons in dorsal root ganglia (DRG) and spinal cord. In naive rats, ATF3 was not expressed in the DRG and spinal cord. Following the cut of peripheral nerve, ATF3 was immediately induced in virtually all DRG neurons and motoneurons that were axotomized, and the time course of induction was dependent on the distance between the injury site and the cell body. Double labeling using immunohistochemistry revealed that the population of DRG neurons expressing ATF3 included those expressing c-jun, and in motoneurons ATF3 and c-jun were concurrently expressed after axotomy. In contrast to c-jun, ATF3 was not induced transsynaptically in spinal dorsal horn neurons. We conclude that ATF3 is specifically induced in sensory and motoneurons in the spinal cord following nerve injury and should be regarded as an unique neuronal marker of nerve injury in the nervous system.},
author = {Tsujino, Hiroaki and Kondo, Eiji and Fukuoka, Tetsuo and Dai, Yi and Tokunaga, Atsushi and Miki, Kenji and Yonenobu, Kazuo and Ochi, Takahiro and Noguchi, Koichi},
doi = {10.1006/mcne.1999.0814},
isbn = {1044-7431 (Print)$\backslash$r1044-7431 (Linking)},
issn = {10447431},
journal = {Molecular and Cellular Neurosciences},
pmid = {10673325},
title = {{Activating transcription factor 3 (ATF3) induction by axotomy in sensory and motoneurons: A novel neuronal marker of nerve injury}},
year = {2000}
}
@article{Braz2010,
abstract = {Although transgenic and knockout mice have helped delineate the mechanisms of action of diverse noxious compounds, it is still difficult to determine unequivocally the subpopulations of primary afferent nociceptor that these molecules engage. As most noxious stimuli lead to tissue and/or nerve injury, here we used induction of activating transcription factor 3 (ATF3), a reliable marker of nerve injury, to assess the populations of primary afferent fibers that are activated after peripheral administration of noxious chemical stimuli. In wild-type mice, hindpaw injections of capsaicin, formalin, mustard oil or menthol induce expression of ATF3 in distinct subpopulations of sensory neurons. Interestingly, even though these noxious chemicals are thought to act through subtypes of transient receptor potential (TRP) channels, all compounds also induced ATF3 in neurons that appear not to express the expected TRP channel subtypes. On the other hand, capsaicin failed to induce ATF3 in mice lacking TRPV1, indicating that TRPV1 is required for both the direct and indirect induction of ATF3 in sensory neurons. By contrast, only low doses of formalin or mustard oil failed to induce ATF3 in TRPA1 null mice, indicating that injections of high doses ({\textgreater}0.5{\%}) of formalin or mustard oil recruit both TRPA1- and non-TRPA1 expressing primary afferent fibers. Finally, peripheral injection of menthol, a TRPM8 receptor agonist, induced ATF3 in a wide variety of sensory neurons, but in a TRPM8-independent manner. We conclude that purportedly selective agonists can activate a heterogeneous population of sensory neurons, which ultimately could contribute to the behavioral responses evoked. {\textcopyright} 2010 International Association for the Study of Pain.},
author = {Br{\'{a}}z, Jo{\~{a}}o M. and Basbaum, Allan I.},
doi = {10.1016/j.pain.2010.05.005},
isbn = {1872-6623 (Electronic)$\backslash$r0304-3959 (Linking)},
issn = {03043959},
journal = {Pain},
keywords = {Capsaicin,DRG,Formalin,Menthol,Mustard oil,Nerve injury,TRPA1,TRPM8,TRPV1},
pmid = {20605331},
title = {{Differential ATF3 expression in dorsal root ganglion neurons reveals the profile of primary afferents engaged by diverse noxious chemical stimuli}},
year = {2010}
}
@article{Rohini2018,
abstract = {Activating transcription factor 3 (ATF3) is a stress-responsive factor that belongs to the activator protein 1 (AP-1) family of transcription factors. ATF3 expression is stimulated by various factors such as hypoxia, cytokines, and chemotherapeutic and DNA damaging agents. Upon stimulation, ATF3 can form homodimers or heterodimers with other members of the AP-1 family to repress or activate transcription. Under physiological conditions, ATF3 expression is transient and plays a pivotal role in controlling the expression of cell-cycle regulators and tumor suppressor, DNA repair, and apoptosis genes. However, under pathological conditions such as those during breast cancer, a sustained and prolonged expression of ATF3 has been observed. In this review, the structure and function of ATF3, its posttranslational modifications (PTM), and its interacting proteins are discussed with a special emphasis on breast cancer metastasis.},
author = {Rohini, M. and {Haritha Menon}, A. and Selvamurugan, N.},
doi = {10.1016/j.ijbiomac.2018.08.107},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/rohini2018.pdf:pdf},
issn = {18790003},
journal = {International Journal of Biological Macromolecules},
keywords = {ATF3,Breast cancer,Runx2},
pages = {310--317},
pmid = {30144543},
publisher = {Elsevier B.V.},
title = {{Role of activating transcription factor 3 and its interacting proteins under physiological and pathological conditions}},
url = {https://doi.org/10.1016/j.ijbiomac.2018.08.107},
volume = {120},
year = {2018}
}
@article{Samaga2009,
abstract = {The epidermal growth factor receptor (EGFR) signaling pathway is probably the best-studied receptor system in mammalian cells, and it also has become a popular example for employing mathematical modeling to cellular signaling networks. Dynamic models have the highest explanatory and predictive potential; however, the lack of kinetic information restricts current models of EGFR signaling to smaller sub-networks. This work aims to provide a large-scale qualitative model that comprises the main and also the side routes of EGFR/ErbB signaling and that still enables one to derive important functional properties and predictions. Using a recently introduced logical modeling framework, we first examined general topological properties and the qualitative stimulus-response behavior of the network. With species equivalence classes, we introduce a new technique for logical networks that reveals sets of nodes strongly coupled in their behavior. We also analyzed a model variant which explicitly accounts for uncertainties regarding the logical combination of signals in the model. The predictive power of this model is still high, indicating highly redundant sub-structures in the network. Finally, one key advance of this work is the introduction of new techniques for assessing high-throughput data with logical models (and their underlying interaction graph). By employing these techniques for phospho-proteomic data from primary hepatocytes and the HepG2 cell line, we demonstrate that our approach enables one to uncover inconsistencies between experimental results and our current qualitative knowledge and to generate new hypotheses and conclusions. Our results strongly suggest that the Rac/Cdc42 induced p38 and JNK cascades are independent of PI3K in both primary hepatocytes and HepG2. Furthermore, we detected that the activation of JNK in response to neuregulin follows a PI3K-dependent signaling pathway.},
author = {Samaga, Regina and Saez-Rodriguez, Julio and Alexopoulos, Leonidas G. and Sorger, Peter K. and Klamt, Steffen},
doi = {10.1371/journal.pcbi.1000438},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/journal.pcbi.1000438.PDF:PDF},
isbn = {1553-7358 (Electronic)$\backslash$r1553-734X (Linking)},
issn = {1553734X},
journal = {PLoS Computational Biology},
number = {8},
pmid = {19662154},
title = {{The logic of EGFR/ErbB signaling: Theoretical properties and analysis of high-throughput data}},
volume = {5},
year = {2009}
}
@article{Laplante2009,
abstract = {Syndecan-4, a ubiquitous cell surface proteoglycan, mediates numerous cellular processes through signaling pathways that affect cellular proliferation, migration, mechanotransduction and endocytosis. These effects are achieved through syndecan-4 functioning as both a co-receptor for the fibroblast growth factor receptors (FGFR1-FGFR4) and its ability to independently activate signaling pathways upon ligand binding. As an FGFR co-receptor, syndecan-4 strengthens the duration and intensity of downstream signaling upon ligand binding; this is particularly evident with regard to mitogen-activated protein kinase (MAPK) signaling. In contrast, syndecan-4 also functions as an independent receptor for heparin-binding growth factors, such as fibroblast growth factors (FGFs), vascular endothelial growth factors (VEGFs) and platelet-derived growth factors (PDGFs). These signaling cascades affect canonical signaling components, such as the mammalian target of rapamycin (mTOR), AKT1 and the Rho family of GTPases. In combination with the integrin family of proteins, syndecan-4 is also able to form physical connections between the extracellular matrix (ECM) and cytoskeletal signaling proteins, and it has a key role in regulation of integrin turnover. This unique versatility of the interactions of syndecan-4 is characterized in this Cell Science at a Glance article and illustrated in the accompanying poster.},
author = {Laplante, M. and Sabatini, D. M.},
doi = {10.1242/jcs.051011},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/3589.full.pdf:pdf},
isbn = {1477-9137 (Electronic)$\backslash$r0021-9533 (Linking)},
issn = {0021-9533},
journal = {Journal of Cell Science},
number = {20},
pages = {3589--3594},
pmid = {19812304},
title = {{mTOR signaling at a glance}},
url = {http://jcs.biologists.org/cgi/doi/10.1242/jcs.051011},
volume = {122},
year = {2009}
}
@article{Averous2008,
abstract = {There is currently substantial interest in the regulation of cell function by mammalian target of rapamycin (mTOR), especially effects linked to the rapamycin-sensitive mTOR complex 1 (mTORC1). Rapamycin induces G(1) arrest and blocks proliferation of many tumor cells, suggesting that the inhibition of mTORC1 signaling may be useful in cancer therapy. In MCF7 breast adenocarcinoma cells, rapamycin decreases levels of cyclin D1, without affecting cytoplasmic levels of its mRNA. In some cell-types, rapamycin does not affect cyclin D1 levels, whereas the starvation for leucine (which impairs mTORC1 signaling more profoundly than rapamycin) does. This pattern correlates with the behavior of eukaryotic initiation factor 4E-binding protein 1 (4E-BP1, an mTORC1 target that regulates translation initiation). siRNA-mediated knock-down of 4E-BP1 abrogates the effect of rapamycin on cyclin D1 expression and increases the polysomal association of the cyclin D1 mRNA. Our data identify 4E-BP1 as a key regulator of cyclin D1 expression, indicate that this effect is not mediated through the changes in cytoplasmic levels of cyclin D1 mRNA and suggest that, in some cell types, interfering with the amino acid input to mTORC1, rather than using rapamycin, may inhibit proliferation.},
author = {Averous, J. and Fonseca, B. D. and Proud, C. G.},
doi = {10.1038/sj.onc.1210715},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/1210715.pdf:pdf},
isbn = {1476-5594 (Electronic)},
issn = {09509232},
journal = {Oncogene},
keywords = {4E-BP1,Cancer,Cell cycle,Rapamycin,Translation initiation},
number = {8},
pages = {1106--1113},
pmid = {17724476},
title = {{Regulation of cyclin D1 expression by mTORC1 signaling requires eukaryotic initiation factor 4E-binding protein 1}},
volume = {27},
year = {2008}
}
@article{Samaga2009a,
abstract = {The epidermal growth factor receptor (EGFR) signaling pathway is probably the best-studied receptor system in mammalian cells, and it also has become a popular example for employing mathematical modeling to cellular signaling networks. Dynamic models have the highest explanatory and predictive potential; however, the lack of kinetic information restricts current models of EGFR signaling to smaller sub-networks. This work aims to provide a large-scale qualitative model that comprises the main and also the side routes of EGFR/ErbB signaling and that still enables one to derive important functional properties and predictions. Using a recently introduced logical modeling framework, we first examined general topological properties and the qualitative stimulus-response behavior of the network. With species equivalence classes, we introduce a new technique for logical networks that reveals sets of nodes strongly coupled in their behavior. We also analyzed a model variant which explicitly accounts for uncertainties regarding the logical combination of signals in the model. The predictive power of this model is still high, indicating highly redundant sub-structures in the network. Finally, one key advance of this work is the introduction of new techniques for assessing high-throughput data with logical models (and their underlying interaction graph). By employing these techniques for phospho-proteomic data from primary hepatocytes and the HepG2 cell line, we demonstrate that our approach enables one to uncover inconsistencies between experimental results and our current qualitative knowledge and to generate new hypotheses and conclusions. Our results strongly suggest that the Rac/Cdc42 induced p38 and JNK cascades are independent of PI3K in both primary hepatocytes and HepG2. Furthermore, we detected that the activation of JNK in response to neuregulin follows a PI3K-dependent signaling pathway.},
author = {Samaga, Regina and Saez-Rodriguez, Julio and Alexopoulos, Leonidas G and Sorger, Peter K and Klamt, Steffen},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/journal.pcbi.1000438.s005(Logical{\_}EgfrModel).PDF:PDF},
journal = {PLoS Computational Biology},
keywords = {Algorithms,Biological,Cell Line,Computational Biology,Computational Biology: methods,Computer Simulation,Databases,Epidermal Growth Factor,Epidermal Growth Factor: chemistry,Epidermal Growth Factor: metabolism,Factual,Feedback,Hepatocytes,Hepatocytes: enzymology,Hepatocytes: metabolism,Humans,Liver Neoplasms,Liver Neoplasms: enzymology,Liver Neoplasms: metabolism,Models,Physiological,Protein Interaction Mapping,Protein Interaction Mapping: methods,Receptor,Signal Transduction,Tumor},
number = {8},
title = {{Table S1 . 1 . List of species in the logical EGFR / ErbB model .}},
volume = {5},
year = {2009}
}
@article{Wee2017,
abstract = {The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is commonly upregulated in cancers such as in non-small-cell lung cancer, metastatic colorectal cancer, glioblastoma, head and neck cancer, pancreatic cancer, and breast cancer. Various mechanisms mediate the upregulation of EGFR activity, including common mutations and truncations to its extracellular domain, such as in the EGFRvIII truncations, as well as to its kinase domain, such as the L858R and T790M mutations, or the exon 19 truncation. These EGFR aberrations over-activate downstream pro-oncogenic signaling pathways, including the RAS-RAF-MEK-ERK MAPK and AKT-PI3K-mTOR pathways. These pathways then activate many biological outputs that are beneficial to cancer cell proliferation, including their chronic initiation and progression through the cell cycle. Here, we review the molecular mechanisms that regulate EGFR signal transduction, including the EGFR structure and its mutations, ligand binding and EGFR dimerization, as well as the signaling pathways that lead to G1 cell cycle progression. We focus on the induction of CYCLIN D expression, CDK4/6 activation, and the repression of cyclin-dependent kinase inhibitor proteins (CDKi) by EGFR signaling pathways. We also discuss the successes and challenges of EGFR-targeted therapies, and the potential for their use in combination with CDK4/6 inhibitors.},
author = {Wee, Ping and Wang, Zhixiang},
doi = {10.3390/cancers9050052},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/cancers-09-00052.pdf:pdf},
issn = {20726694},
journal = {Cancers},
keywords = {AKT,Cell cycle,Cell proliferation,ERK,Epidermal growth factor receptor,ErBB,G1,Signal transduction},
number = {5},
pages = {1--45},
pmid = {28513565},
title = {{Epidermal growth factor receptor cell proliferation signaling pathways}},
volume = {9},
year = {2017}
}
@article{Wang2007,
abstract = {Mammalian target of rapamycin (mTOR) functions in two distinct signaling complexes, mTORC1 and mTORC2. In response to insulin and nutrients, mTORC1, consisting of mTOR, raptor (regulatory-associated protein of mTOR), and mLST8, is activated and phosphorylates eukaryotic initiation factor 4E-binding protein (4EBP) and p70 S6 kinase to promote protein synthesis and cell size. Previously we found that activation of mTOR kinase in response to insulin was associated with increased 4EBP1 binding to raptor. Here we identify prolinerich Akt substrate 40 (PRAS40) as a binding partner for mTORC1. A putative TOR signaling motif, FVMDE, is identified in PRAS40 and shown to be required for interaction with raptor. Insulin stimulation markedly decreases the level of PRAS40 bound by mTORC1. Recombinant PRAS40 inhibits mTORC1 kinase activity in vivo and in vitro, and this inhibition depends on PRAS40 association with raptor. Furthermore, decreasing PRAS40 expression by short hairpin RNA enhances 4E-BP1 binding to raptor, and recombinant PRAS40 competes with 4E-BP1 binding to raptor. We, therefore, propose that PRAS40 regulates mTORC1 kinase activity by functioning as a direct inhibitor of substrate binding.},
author = {Wang, Lifu and Harris, Thurl E. and Roth, Richard A. and Lawrence, John C.},
doi = {10.1074/jbc.M702376200},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/J. Biol. Chem.-2007-Wang-20036-44.pdf:pdf},
isbn = {4349241582},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {17510057},
title = {{PRAS40 regulates mTORC1 kinase activity by functioning as a direct inhibitor of substrate binding}},
year = {2007}
}
@article{Urbanska2012,
abstract = {Dendrites are the main site of information input into neurons. Their development is a multistep process controlled by mammalian target of rapamycin (mTOR) among other proteins. mTOR is a serine/threonine protein kinase that forms two functionally distinct complexes in mammalian cells: mTORC1 and mTORC2. However, the one that contributes to mammalian neuron development remains unknown. This work used short hairpin RNA against Raptor and Rictor, unique components of mTORC1 and mTORC2, respectively, to dissect mTORC involvement in this process. We provide evidence that both mTOR complexes are crucial for the proper dendritic arbor morphology of hippocampal neurons. These two complexes are required for dendritic development both under basal conditions and upon the induction of mTOR-dependent dendritic growth. We also identified Akt as a downstream effector of mTORC2 needed for proper dendritic arbor morphology, the action of which required mTORC1 and p70S6K1.},
author = {Urbanska, Malgorzata and Gozdz, Agata and Swiech, Lukasz J. and Jaworski, Jacek},
doi = {10.1074/jbc.M112.374405},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/J. Biol. Chem.-2012-Urbanska-30240-56.pdf:pdf},
isbn = {4822597075},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {22810227},
title = {{Mammalian target of rapamycin complex 1 (mTORC1) and 2 (mTORC2) control the dendritic arbor morphology of hippocampal neurons}},
year = {2012}
}
@article{Oda2005,
abstract = {The epidermal growth factor receptor (EGFR) signaling pathway is one of the most important pathways that regulate growth, survival, proliferation, and differentiation in mammalian cells. Reflecting this importance, it is one of the best-investigated signaling systems, both experimentally and computationally, and several computational models have been developed for dynamic analysis. A map of molecular interactions of the EGFR signaling system is a valuable resource for research in this area. In this paper, we present a comprehensive pathway map of EGFR signaling and other related pathways. The map reveals that the overall architecture of the pathway is a bow-tie (or hourglass) structure with several feedback loops. The map is created using CellDesigner software that enables us to graphically represent interactions using a well-defined and consistent graphical notation, and to store it in Systems Biology Markup Language (SBML).},
author = {Oda, Kanae and Matsuoka, Yukiko and Funahashi, Akira and Kitano, Hiroaki},
doi = {10.1038/msb4100014},
file = {:Users/ozlem/Library/Application Support/Mendeley Desktop/Downloaded/Oda et al. - 2005 - A comprehensive pathway map of epidermal growth factor receptor signaling.pdf:pdf},
isbn = {1744-4292 (Electronic)$\backslash$r1744-4292 (Linking)},
issn = {1744-4292},
journal = {Molecular Systems Biology},
number = {1},
pages = {E1--E17},
pmid = {16729045},
title = {{A comprehensive pathway map of epidermal growth factor receptor signaling}},
url = {http://msb.embopress.org/cgi/doi/10.1038/msb4100014},
volume = {1},
year = {2005}
}
@article{Peterson2009,
abstract = {The mTORC1 and mTORC2 pathways regulate cell growth, proliferation, and survival. We identify DEPTOR as an mTOR-interacting protein whose expression is negatively regulated by mTORC1 and mTORC2. Loss of DEPTOR activates S6K1, Akt, and SGK1, promotes cell growth and survival, and activates mTORC1 and mTORC2 kinase activities. DEPTOR overexpression suppresses S6K1 but, by relieving feedback inhibition from mTORC1 to PI3K signaling, activates Akt. Consistent with many human cancers having activated mTORC1 and mTORC2 pathways, DEPTOR expression is low in most cancers. Surprisingly, DEPTOR is highly overexpressed in a subset of multiple myelomas harboring cyclin D1/D3 or c-MAF/MAFB translocations. In these cells, high DEPTOR expression is necessary to maintain PI3K and Akt activation and a reduction in DEPTOR levels leads to apoptosis. Thus, we identify a novel mTOR-interacting protein whose deregulated overexpression in multiple myeloma cells represents a mechanism for activating PI3K/Akt signaling and promoting cell survival. {\textcopyright} 2009 Elsevier Inc. All rights reserved.},
author = {Peterson, Timothy R. and Laplante, Mathieu and Thoreen, Carson C. and Sancak, Yasemin and Kang, Seong A. and Kuehl, W. Michael and Gray, Nathanael S. and Sabatini, David M.},
doi = {10.1016/j.cell.2009.03.046},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/PIIS0092867409003894.pdf:pdf},
isbn = {1097-4172 (Electronic)$\backslash$n0092-8674 (Linking)},
issn = {00928674},
journal = {Cell},
keywords = {HUMDISEASE,SIGNALING},
pmid = {19446321},
title = {{DEPTOR Is an mTOR Inhibitor Frequently Overexpressed in Multiple Myeloma Cells and Required for Their Survival}},
year = {2009}
}
@article{Nelson2012,
archivePrefix = {arXiv},
arxivId = {NIHMS150003},
author = {Nelson, Eric E and Guyer, Amanda E},
doi = {10.1016/j.dcn.2011.01.002.The},
eprint = {NIHMS150003},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/nihms-629610.pdf:pdf},
isbn = {6176321972},
issn = {15378276},
keywords = {adolescence,affiliative,childhood,emotion},
number = {3},
pages = {233--245},
title = {{NIH Public Access}},
volume = {1},
year = {2012}
}
@article{Klamt2006a,
abstract = {BACKGROUND: Structural analysis of cellular interaction networks contributes to a deeper understanding of network-wide interdependencies, causal relationships, and basic functional capabilities. While the structural analysis of metabolic networks is a well-established field, similar methodologies have been scarcely developed and applied to signaling and regulatory networks. RESULTS: We propose formalisms and methods, relying on adapted and partially newly introduced approaches, which facilitate a structural analysis of signaling and regulatory networks with focus on functional aspects. We use two different formalisms to represent and analyze interaction networks: interaction graphs and (logical) interaction hypergraphs. We show that, in interaction graphs, the determination of feedback cycles and of all the signaling paths between any pair of species is equivalent to the computation of elementary modes known from metabolic networks. Knowledge on the set of signaling paths and feedback loops facilitates the computation of intervention strategies and the classification of compounds into activators, inhibitors, ambivalent factors, and non-affecting factors with respect to a certain species. In some cases, qualitative effects induced by perturbations can be unambiguously predicted from the network scheme. Interaction graphs however, are not able to capture AND relationships which do frequently occur in interaction networks. The consequent logical concatenation of all the arcs pointing into a species leads to Boolean networks. For a Boolean representation of cellular interaction networks we propose a formalism based on logical (or signed) interaction hypergraphs, which facilitates in particular a logical steady state analysis (LSSA). LSSA enables studies on the logical processing of signals and the identification of optimal intervention points (targets) in cellular networks. LSSA also reveals network regions whose parametrization and initial states are crucial for the dynamic behavior. We have implemented these methods in our software tool CellNetAnalyzer (successor of FluxAnalyzer) and illustrate their applicability using a logical model of T-Cell receptor signaling providing non-intuitive results regarding feedback loops, essential elements, and (logical) signal processing upon different stimuli. CONCLUSION: The methods and formalisms we propose herein are another step towards the comprehensive functional analysis of cellular interaction networks. Their potential, shown on a realistic T-cell signaling model, makes them a promising tool.},
author = {Klamt, Steffen and Saez-Rodriguez, Julio and Lindquist, Jonathan A. and Simeoni, Luca and Gilles, Ernst D.},
doi = {10.1186/1471-2105-7-56},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/klamt2006.pdf:pdf},
isbn = {1471-2105 (Electronic)$\backslash$n1471-2105 (Linking)},
issn = {14712105},
journal = {BMC Bioinformatics},
pmid = {16464248},
title = {{A methodology for the structural and functional analysis of signaling and regulatory networks}},
volume = {7},
year = {2006}
}
@article{Hay2004,
author = {Hay, N. and Sonenberg, N.},
doi = {10.1101/gad.1212704.hibiting},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/Genes Dev.-2004-Hay-1926-45.pdf:pdf},
journal = {Genes Dev},
keywords = {4e-bp,akt,eif4e,rheb,s6k,tsc1,tsc2},
pages = {1926--1945},
title = {{Upstream and downstream of mTOR. Genes Dev. 2004, 18, 1926–1945}},
volume = {18},
year = {2004}
}
@article{Sarbassov2005,
abstract = {Deregulation of Akt/protein kinase B (PKB) is implicated in the pathogenesis of cancer and diabetes. Akt/PKB activation requires the phosphorylation of Thr308 in the activation loop by the phosphoinositide-dependent kinase 1 (PDK1) and Ser473 within the carboxyl-terminal hydrophobic motif by an unknown kinase. We show that in Drosophila and human cells the target of rapamycin (TOR) kinase and its associated protein rictor are necessary for Ser473 phosphorylation and that a reduction in rictor or mammalian TOR (mTOR) expression inhibited an Akt/PKB effector. The rictor-mTOR complex directly phosphorylated Akt/PKB on Ser473 in vitro and facilitated Thr308 phosphorylation by PDK1. Rictor-mTOR may serve as a drug target in tumors that have lost the expression of PTEN, a tumor suppressor that opposes Akt/PKB activation.},
author = {Sarbassov, Dos D. and Guertin, David A. and Ali, Siraj M. and Sabatini, David M.},
doi = {10.1126/science.1106148},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/sarbassov2005.pdf:pdf},
isbn = {1095-9203 (Electronic)$\backslash$r0036-8075 (Linking)},
issn = {00368075},
journal = {Science},
number = {5712},
pages = {1098--1101},
pmid = {15718470},
title = {{Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex}},
volume = {307},
year = {2005}
}
@article{Kakumoto2015,
abstract = {The activity of the mechanistic target of rapamycin (mTOR) is elevated in various types of human cancers, implicating a role in tumor progression. However, the molecular mechanisms underlying mTOR upregulation remain unclear. In this study, we found that the expression of mLST8, a required subunit of both mTOR complex 1 (mTORC1) and complex 2 (mTORC2), was upregulated in several human colon and prostate cancer cell lines and tissues. Knockdown of mLST8 significantly suppressed mTORC1 and mTORC2 complex formation, and it also inhibited tumor growth and invasiveness in human colon carcinoma (HCT116) and prostate cancer (LNCaP) cells. Overexpression of mLST8 induced anchorage-independent cell growth in normal epithelial cells (HaCaT), although mLST8 knockdown had no effect on normal cell growth. mLST8 knockdown reduced mTORC2-mediated phosphorylation of AKT in both cancer and normal cells, whereas it potently inhibited mTORC1-mediated phosphorylation of 4E-BP1 specifically in cancer cells. These results suggest that mLST8 plays distinct roles in normal and cancer cells, depending upon its expression level, and that mLST8 upregulation may contribute to tumor progression by constitutively activating both the mTORC1 and mTORC2 pathways.},
author = {Kakumoto, Kyoko and Ikeda, Jun Ichiro and Okada, Masato and Morii, Eiichi and Oneyama, Chitose},
doi = {10.1371/journal.pone.0119015},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/kakumoto2015.pdf:pdf},
isbn = {10.1371/journal.pone.0119015},
issn = {19326203},
journal = {PLoS ONE},
pmid = {25906254},
title = {{MLST8 promotes mTOR-mediated tumor progression}},
year = {2015}
}
@article{Oneyama2011,
abstract = {The tyrosine kinase c-Src is upregulated in various human cancers, but the molecular mechanisms underlying c-Src-mediated tumor growth remain unclear. Here we examined the involvement of microRNAs in the c-Src-mediated tumor growth. Microarray profiling revealed that c-Src activation downregulates a limited set of microRNAs, including miR-99a, which targets oncogenic mammalian target of rapamycin (mTOR) and fibroblast growth factor receptor 3 (FGFR3). Re-expression of miR-99a suppressed tumor growth of c-Src-transformed cells, and this effect was restored by the overexpression of mTOR. The downregulation of miR-99a was also observed in epidermal growth factor- and Ras-transformed cells, and it was suppressed by inhibiting the mitogen-activated protein kinase (MAPK) pathway. Furthermore, miR-99a downregulation is associated with mTOR/FGFR3 upregulation in various human lung cancer cells/tissues. The tumorigenicity of these cells was suppressed by the introduction of miR-99a. These findings suggest that the miR-99a-mTOR/FGFR3 pathway is crucial for controlling tumor growth in a wide range of human cancers that harbor upregulation of the Src-related oncogenic pathways.},
author = {Oneyama, C. and Ikeda, J. and Okuzaki, D. and Suzuki, K. and Kanou, T. and Shintani, Y. and Morii, E. and Okumura, M. and Aozasa, K. and Okada, M.},
doi = {10.1038/onc.2011.63},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/onc201163.pdf:pdf},
isbn = {1476-5594 (Electronic)$\backslash$r0950-9232 (Linking)},
issn = {09509232},
journal = {Oncogene},
keywords = {FGFR3,c-Src,mTOR,miRNA,tumor},
number = {32},
pages = {3489--3501},
pmid = {21383697},
publisher = {Nature Publishing Group},
title = {{MicroRNA-mediated downregulation of mTOR/FGFR3 controls tumor growth induced by Src-related oncogenic pathways}},
url = {http://dx.doi.org/10.1038/onc.2011.63},
volume = {30},
year = {2011}
}
@article{Herbst2004,
abstract = {The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein that constitutes one of four members of the erbB family of tyrosine kinase receptors. Binding of EGFR to its cognate ligands leads to autophosphorylation of receptor tyrosine kinase and subsequent activation of signal transduction pathways that are involved in regulating cellular proliferation, differentiation, and survival. Although present in normal cells, EGFR is overexpressed in a variety of tumor cell lines and has been associated with poor prognosis and decreased survival. EGFR activation also plays a role in resistance to chemotherapy and radiation treatment in tumor cells. Over the past two decades, much effort has been directed at developing anticancer agents that can interfere with EGFR activity. The most common pharmacologic approaches to inhibiting EGFR have been to develop monoclonal antibodies and small-molecule inhibitors. Monoclonal antibodies block ligand binding to the extracellular domain, whereas the small-molecule inhibitors exert their effects at the intracellular portion of the receptor to prevent tyrosine kinase phosphorylation and subsequent activation of signal transduction pathways. A number of EGFR inhibitors have been developed that can arrest tumor growth and, in some cases, cause tumor regression. When used in combination with cytotoxic treatments, chemotherapy, and radiation, EGFR inhibitors have been able to potentiate their anticancer activity. {\textcopyright} 2004 Elsevier Inc.},
archivePrefix = {arXiv},
arxivId = {arXiv:1011.1669v3},
author = {Herbst, Roy S.},
doi = {10.1016/j.ijrobp.2003.11.041},
eprint = {arXiv:1011.1669v3},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/PIIS0360301604003311.pdf:pdf},
isbn = {0360-3016},
issn = {03603016},
journal = {International Journal of Radiation Oncology Biology Physics},
keywords = {ABX-EGF,CI-1033,Epidermal growth factor receptor (EGFR),IMC-C225,OSI-774,ZD1839},
number = {2 SUPPL.},
pages = {21--26},
pmid = {15142631},
title = {{Review of epidermal growth factor receptor biology}},
volume = {59},
year = {2004}
}
@article{Woo2007,
abstract = {The protein kinase mammalian target of rapamycin (mTOR) plays an important role in the coordinate regulation of cellular responses to nutritional and growth factor conditions. mTOR achieves these roles through interacting with raptor and rictor to form two distinct protein complexes, mTORC1 and mTORC2. Previous studies have been focused on mTORC1 to elucidate the central roles of the complex in mediating nutritional and growth factor signals to the protein synthesis machinery. Functions of mTORC2, relative to mTORC1, have remained little understood. Here we report identification of a novel component of mTORC2 named PRR5 (PRoline-Rich protein 5), a protein encoded by a gene located on a chromosomal region frequently deleted during breast and colorectal carcinogenesis (Johnstone, C. N., Castellvi-Bel, S., Chang, L. M., Sung, R. K., Bowser, M. J., Pique, J. M., Castells, A., and Rustgi, A. K. (2005) Genomics 85, 338-351). PRR5 interacts with rictor, but not raptor, and the interaction is independent of mTOR and not disturbed under conditions that disrupt the mTOR-rictor interaction. PRR5, unlike Sin1, another component of mTORC2, is not important for the mTOR-rictor interaction and mTOR activity toward Akt phosphorylation. Despite no significant effect of PRR5 on mTORC2-mediated Akt phosphorylation, PRR5 silencing inhibits Akt and S6K1 phosphorylation and reduces cell proliferation rates, a result consistent with PRR5 roles in cell growth and tumorigenesis. The inhibition of Akt and S6K1 phosphorylation by PRR5 knock down correlates with reduction in the expression level of platelet-derived growth factor receptor beta (PDGFRbeta). PRR5 silencing impairs PDGF-stimulated phosphorylation of S6K1 and Akt but moderately reduces epidermal growth factor- and insulin-stimulated phosphorylation. These findings propose a potential role of mTORC2 in the cross-talk with the cellular machinery that regulates PDGFRbeta expression and signaling.},
author = {Woo, So Yon and Kim, Dong Hwan and Jun, Chang Bong and Kim, Young Mi and Haar, Emilie Vander and Lee, Seong Il and Hegg, James W. and Bandhakavi, Sricharan and Griffin, Timothy J. and Kim, Do Hyung},
doi = {10.1074/jbc.M704343200},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/J. Biol. Chem.-2007-Woo-25604-12.pdf:pdf},
isbn = {0021-9258 (Print)$\backslash$r0021-9258 (Linking)},
issn = {00219258},
journal = {Journal of Biological Chemistry},
number = {35},
pages = {25604--25612},
pmid = {17599906},
title = {{PRR5, a novel component of mTOR complex 2, regulates platelet-derived growth factor receptor $\beta$ expression and signaling}},
volume = {282},
year = {2007}
}
@article{Caron2015,
abstract = {DEP domain-containing mTOR-interacting protein (DEPTOR) has been recently discovered as an endogenous regulator of the mechanistic target of rapamycin complex 1 (mTORC1) and mTORC2. mTORC1 is present in the brain, and there is growing evidence that its dysregulation contributes to several brain alterations. This suggests the involvement of mTOR signaling and its modulators in neurobiological controls. Here, we characterized and mapped the expression of DEPTOR in the rat brain. We show that DEPTOR was widely expressed from the forebrain to the hindbrain, including the hippocampus, the mediobasal hypothalamus, and the circumventricular organs (CVOs). In the hippocampus, DEPTOR protein and Deptor mRNA were highly expressed in the dendate gyrus and CA3 field. In the CVOs, DEPTOR was expressed in the subfornical organ, the median eminence, and the area postrema. In the mediobasal hypothalamus, DEPTOR was expressed in neurons of the ventromedial nucleus (VMH) and colocalized with proopiomelanocortin (POMC) in the arcuate nucleus (ARC). The hypothalamic distribution suggested a role for DEPTOR in energy balance. Supporting this possibility, we observed that Deptor hypothalamic expression was modulated by the nutritional status in a context of diet-induced and genetic obesity; food deprivation increased Deptor mRNA in both the ARC and VMH of obese rats. In conclusion, the present results illustrate the presence of DEPTOR in the rat brain and suggest a role for DEPTOR in the hypothalamic regulation of energy balance, which further supports the role of mTOR in energy homeostasis. J. Comp. Neurol. 523:93-107, 2015. {\textcopyright} 2014 Wiley Periodicals, Inc.},
author = {Caron, Alexandre and Baraboi, Elena Dana and Laplante, Mathieu and Richard, Denis},
doi = {10.1002/cne.23668},
file = {:Users/ozlem/Downloads/DEP{\_}Domain-Containing{\_}mTOR-Interacting{\_}Protein{\_}in{\_}.pdf:pdf},
isbn = {1096-9861 (Electronic)$\backslash$n0021-9967 (Linking)},
issn = {10969861},
journal = {Journal of Comparative Neurology},
keywords = {DEPTOR,Energy balance,Hypothalamus,In situ hybridization,MTOR,Obesity},
number = {1},
pages = {93--107},
pmid = {25159114},
title = {{DEP domain-containing mTOR-interacting protein in the rat brain: Distribution of expression and potential implication}},
volume = {523},
year = {2015}
}
@article{Harris2003a,
abstract = {The mammalian target of rapamycin, mTOR, is a protein Ser-Thr kinase that functions as a central element in a signaling pathway involved in the control of cell growth and proliferation. The activity of mTOR is controlled not only by amino acids, but also by hormones and growth factors that activate the protein kinase Akt. The signaling pathway downstream of Akt leading to mTOR involves the protein products of the genes mutated in tuberous sclerosis, TSC1 and TSC2, and the small guanosine triphosphatase, Rheb. In cells, mTOR is found in a complex with two other proteins, raptor and mLST8. In this review, we describe recent progress in understanding the control of the mTOR signaling pathway and the role of mTOR-interacting proteins.},
author = {Harris, T. E. and Lawrence, J. C.},
doi = {10.1126/stke.2122003re15},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/harris2003.pdf:pdf},
isbn = {1525-8882 (Electronic)$\backslash$r1525-8882 (Linking)},
issn = {1945-0877},
journal = {Science Signaling},
number = {212},
pages = {re15--re15},
pmid = {14668532},
title = {{TOR Signaling}},
url = {http://stke.sciencemag.org/cgi/doi/10.1126/stke.2122003re15},
volume = {2003},
year = {2003}
}
@article{Buerger2003,
abstract = {Receptor tyrosine kinases of the epidermal growth factor (EGF) receptor family regulate essential cellular functions such as proliferation, survival, migration, and differentiation but also play central roles in the etiology and progression of tumors. We have identified short peptide sequences from a random peptide library integrated into the thioredoxin scaffold protein, which specifically bind to the intracellular domain of the EGF receptor (EGFR). These molecules have the potential to selectively inhibit specific aspects of EGF receptor signaling and might become valuable as anticancer agents. Intracellular expression of the aptamer encoding gene construct KDI1 or introduction of bacterially expressed KDI1 via a protein transduction domain into EGFR-expressing cells results in KDI1.EGF receptor complex formation, a slower proliferation, and reduced soft agar colony formation. Aptamer KDI1 did not summarily block the EGF receptor tyrosine kinase activity but selectively interfered with the EGF-induced phosphorylation of the tyrosine residues 845, 1068, and 1148 as well as the phosphorylation of tyrosine 317 of p46 Shc. EGF-induced phosphorylation of Stat3 at tyrosine 705 and Stat3-dependent transactivation were also impaired. Transduction of a short synthetic peptide aptamer sequence not embedded into the scaffold protein resulted in the same impairment of EGF-induced Stat3 activation.},
author = {Buerger, Claudia and Nagel-Wolfrum, Kerstin and Kunz, Christian and Wittig, Ilka and Butz, Karin and Hoppe-Seyler, Felix and Groner, Bernd},
doi = {10.1074/jbc.M301629200},
file = {:Users/ozlem/Dropbox/Egfr Models/Papers and Supp/J. Biol. Chem.-2003-Buerger-37610-21.pdf:pdf},
isbn = {0021-9258 (Print)},
issn = {00219258},
journal = {Journal of Biological Chemistry},
pmid = {12842895},
title = {{Sequence-specific peptide aptamers, interacting with the intracellular domain of the epidermal growth factor receptor, interfere with Stat3 activation and inhibit the growth of tumor cells}},
year = {2003}
}