From 66244dedb78ea81ad5f2135212d87298a147775c Mon Sep 17 00:00:00 2001 From: Brendan Larsen Date: Wed, 10 Apr 2024 08:10:11 -0700 Subject: [PATCH] update readme in filtered_data/ --- docs/.vitepress/dist/.DS_Store | Bin 10244 -> 12292 bytes docs/.vitepress/dist/404.html | 2 +- docs/.vitepress/dist/antibody_escape.html | 2 +- docs/.vitepress/dist/cell_entry.html | 2 +- docs/.vitepress/dist/hashmap.json | 2 +- docs/.vitepress/dist/heatmaps.html | 2 +- .../dist/htmls/E2_binding_heatmap.html | 73 +-- .../dist/htmls/E2_entry_heatmap.html | 72 +-- .../dist/htmls/E3_binding_heatmap.html | 73 +-- .../dist/htmls/E3_entry_heatmap.html | 73 +-- docs/.vitepress/dist/index.html | 2 +- docs/.vitepress/dist/interactive.html | 2 +- .../dist/notebooks/analyze_escape_data.html | 138 +++--- .../dist/notebooks/ephrin_binding.html | 455 +++++++++++------- .../dist/notebooks/filter_data.html | 326 +++++++++++-- .../dist/notebooks/interactive_figures.html | 194 ++++---- .../dist/notebooks/mapping_site_level.html | 2 +- .../notebooks/nipah_RBP_entry_analysis.html | 110 ++--- .../dist/notebooks/plot_heatmaps.html | 206 ++++---- .../.vitepress/dist/pipeline_information.html | 2 +- docs/.vitepress/dist/receptor_binding.html | 2 +- docs/public/htmls/E2_binding_heatmap.html | 44 +- docs/public/htmls/E2_entry_heatmap.html | 44 +- docs/public/htmls/E3_binding_heatmap.html | 44 +- docs/public/htmls/E3_entry_heatmap.html | 44 +- results/filtered_data/README.md | 7 + .../filtered_data/public_filtered/README.md | 4 + 27 files changed, 1217 insertions(+), 710 deletions(-) create mode 100644 results/filtered_data/README.md create mode 100644 results/filtered_data/public_filtered/README.md diff --git a/docs/.vitepress/dist/.DS_Store b/docs/.vitepress/dist/.DS_Store index 03b503bad070aaf2d3b3e6433035a8265e38959d..eb1fd9fe4e984a80cdae9d36c7654eda2cfaa8c4 100755 GIT binary patch delta 308 zcmZn(Xh~3DU|?W$DortDV9)?EIe-{M3-ADmHUvt0 z&XCGbTozoEH?dH8vVjTv|cOwLf5IeDF+#^e}Tq0Q!^$C%im<^ce-W;_c3 delta 153 zcmZokXbF&DU|?W$DortDU{C-uIe-{M3-C-V6q~3gIoUvmMI6Xy-~nPrpg03VaZ-74 zK~heB(&k2qF7}BJq&Ks3uy8Q)Z01q;$Ubp`%w`^e81~6^5|ad(K^lSPaRUigkeM4V nerKM{ucOPzFxiAhnS%*ppT^`Aotc{%RsS%t0~N9{WHJB%&>|iE diff --git a/docs/.vitepress/dist/404.html b/docs/.vitepress/dist/404.html index 75b5f935..ab41bc23 100644 --- a/docs/.vitepress/dist/404.html +++ b/docs/.vitepress/dist/404.html @@ -15,7 +15,7 @@
Nipah RBP DMS

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404

PAGE NOT FOUND

But if you don't change your direction, and if you keep looking, you may end up where you are heading.
Take me home

Built by Brendan Larsen and Jesse Bloom

- + \ No newline at end of file diff --git a/docs/.vitepress/dist/antibody_escape.html b/docs/.vitepress/dist/antibody_escape.html index 5021e5f6..a4a78871 100644 --- a/docs/.vitepress/dist/antibody_escape.html +++ b/docs/.vitepress/dist/antibody_escape.html @@ -18,7 +18,7 @@
Nipah RBP DMS

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Antibody Escape ​

We determined the effects of mutations on neutralization by different anti-RBP antibodies. Antibody selections were performed by incubating pseudovirus libraries with different concentrations of antibody, followed by infection of CHO-bEFNB3 cells to recover barcodes. Neutralization curves were fit on the DMS data with polyclonal.

Individual Antibody Selections ​

Individual antibody selection model fitting notebooks

LibB-230720-m102.4

LibA-230725-m102.4

LibA-231116-m102.4

LibA-230725-nAH1.3

LibB-230630-nAH1.3

LibB-230720-nAH1.3

LibA-231024-HENV26

LibB-230815-HENV26

LibB-230818-HENV26

LibB-230907-HENV26

LibB-230704-HENV32

LibB-230720-HENV32

LibA-230725-HENV32

LibB-230907-HENV32

LibA-230815-HENV103

LibB-230818-HENV103

LibB-230906-HENV103

LibA-230815-HENV117

LibB-230818-HENV117

LibB-230907-HENV117

Average Antibody Escape ​

Averaging antibody escape across libraries and replicate selections.

Average antibody escape notebooks

m102.4

nAH1.3

HENV-26

HENV-32

HENV-103

HENV-117

Antibody Escape Comprehensive Heatmaps ​

More in-depth heatmaps that allow additional control over filtering parameters

m102.4

HENV-117

HENV-26

HENV-32

HENV-103

nAH1.3

Neutralization Curves ​

Neutralization curves notebook

Neutralization of unmutated Nipah RBP/F pseudovirus by different anti-RBP antibodies.

Antibody Escape Validations ​

Antibody validation notebook

To validate the escape measurements from DMS, we generated single RBP mutant pseudoviruses and tested their neutralization by antibody nAH1.3.

Miscellaneous Figures ​

Escape at Nipah and Hendra polymorphisms and differences

Functional Effect of Antibody Escape Mutations ​

Effects of mutations on cell entry and antibody neutralization

Escape by Site ​

Line plot of average antibody escape at each site

Antibody Escape Analysis Notebook ​

Antibody analysis notebook

Raw Data ​

These data have not been filtered. For filtered .csv files, go to Analysis Pipeline

Individual antibody escape selection .csv files

Average m102.4 escape .csv

Average HENV-117 escape .csv

Average HENV-26 escape .csv

Average HENV-32 escape .csv

Average HENV-103 escape .csv

Average nAH1.3 escape .csv

Built by Brendan Larsen and Jesse Bloom

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Nipah RBP DMS

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Cell Entry ​

To measure the effects of mutations on RBP-mediated cell entry, we performed 'functional selections' where the frequencies of barcodes were compared between particles pseudotyped with either Nipah RBP/F or VSV-G. Notebooks below contain information about each step.

Global Epistasis Fitting ​

Individual cell entry selections were fit with multidms to decompose the effects of individual mutations.

Individual functional selection global epistasis model fitting notebooks

LibA-230725-CHO-bEFNB3

LibA-230815-CHO-bEFNB3

LibA-230818-CHO-bEFNB3

LibA-230825-CHO-bEFNB3

LibA-230916-CHO-bEFNB3

LibA-231006-CHO-bEFNB3

LibA-231019-CHO-bEFNB3_1

LibA-231019-CHO-bEFNB3_2

LibA-231019-CHO-bEFNB2_1

LibA-231024-CHO-bEFNB3

LibA-231024-CHO-bEFNB2

LibA-231112-CHO-bEFNB3_1

LibA-231112-CHO-bEFNB3_2

LibA-231112-CHO-bEFNB2

LibA-231207-CHO-bEFNB2_1

LibA-231207-CHO-bEFNB2_2

LibA-231207-CHO-bEFNB2_3

LibA-231207-CHO-bEFNB2_4

LibA-231207-CHO-bEFNB2_5

LibA-231222-CHO-bEFNB2

LibB-230630-CHO-C6-nac

LibB-230720-CHO-bEFNB3

LibB-230731-CHO-BA6-nac

LibB-230815-CHO-bEFNB3

LibB-230818-CHO-bEFNB3

LibB-230906-CHO-EFNB3-C6_diffVSV

LibB-230907-CHO-EFNB3-C6-nac_diffVSV

LibB-231105-CHO-EFNB2-BA6-nac_diffVSV

LibB-231108-CHO-EFNB2-BA6-nac_diff_VSV

LibB-231108-CHO-EFNB3-C6-nac_diff_VSV

LibB-231112-CHO-bEFNB2

LibB-231112-CHO-EFNB2-BA6-1

LibB-231112-CHO-EFNB2-BA6-2

LibB-231112-CHO-EFNB3-C6-1

LibB-231112-CHO-EFNB3-C6-2

LibB-231116-CHO-bEFNB3

LibB-231116-CHO-bEFNB2

LibB-231116-CHO-BA6_nac_diff_VSV

LibB-231222-CHO-EFNB2-BA6_diffVSV

LibB-231222-CHO-EFNB2-BA6-nac_diffVSV

Averaging Cell Entry ​

Individual functional selections were averaged between libraries and replicates below.

CHO_bEFNB2

CHO_bEFNB3

Comprehensive Cell Entry Heatmaps ​

Additional control over filtering parameters

CHO-bEFNB2 cell entry heatmap

CHO-bEFNB3 cell entry heatmap

Functional Scores ​

Notebook analyzing the distribution of functional scores for all individual selections.

Link to functional scores notebook

Analyze Data ​

Notebook analyzing cell entry from filtered data.

Cell entry analysis notebook

Cell Entry Figures ​

TIP

Plots below are interactive. Hover over points to see more information. Click arrow box to view altair plots in separate page.

Cell entry of different RBP regions

Site-averaged Effects of Mutations on Cell Entry ​

Sites in RBP neck and contact sites (ranked from least constrained to most)

Cell Entry Correlations ​

Correlation between site-averaged effects of mutations on cell entry

Correlation between effects of all mutations on cell entry

Cell Entry Validations ​

Cell entry validation notebook

We validated the DMS cell entry measurements by making individual RBP mutants, expressing them on pseudovirus particles, and measuring luciferase following infection.

Raw Data ​

These data have not been filtered. For filtered .csv files, go to Analysis Pipeline

Individual cell entry .csv files

Average entry in CHO-bEFNB2 cells .csv

Average entry in CHO-bEFNB3 cells .csv

Built by Brendan Larsen and Jesse Bloom

- + \ No newline at end of file diff --git a/docs/.vitepress/dist/hashmap.json b/docs/.vitepress/dist/hashmap.json index be83a21c..fea16525 100644 --- a/docs/.vitepress/dist/hashmap.json +++ b/docs/.vitepress/dist/hashmap.json @@ -1 +1 @@ -{"interactive.md":"D9-gz2zM","pipeline_information.md":"J3K3c1Le","heatmaps.md":"BMScwFVb","index.md":"4RdSqROA","receptor_binding.md":"DrYDW_pu","antibody_escape.md":"Cy_XCdX2","cell_entry.md":"DdwToOv0"} +{"index.md":"4RdSqROA","interactive.md":"D9-gz2zM","heatmaps.md":"BMScwFVb","pipeline_information.md":"J3K3c1Le","receptor_binding.md":"DrYDW_pu","antibody_escape.md":"Cy_XCdX2","cell_entry.md":"DdwToOv0"} diff --git a/docs/.vitepress/dist/heatmaps.html b/docs/.vitepress/dist/heatmaps.html index 9d6363cd..25e8b4e8 100644 --- a/docs/.vitepress/dist/heatmaps.html +++ b/docs/.vitepress/dist/heatmaps.html @@ -18,7 +18,7 @@
Nipah RBP DMS

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Heatmaps ​

Heatmaps represent one of the best ways to explore deep mutational scanning data. This page contains links to heatmaps which show the effects of mutations on three different phenotypes: cell entry, receptor binding, and antibody escape.

TIP

Hover over the heatmaps to see more information about each mutation

Entry Heatmaps ​

Cell Entry in CHO-bEFNB2 Cells

Cell Entry in CHO-bEFNB3 Cells

Binding Heatmaps ​

INFO

Mutations with low cell entry scores are masked in dark gray.

bEFNB2 binding Heatmap

bEFNB3 Binding Heatmap

Antibody Escape Heatmaps ​

INFO

Mutations with low cell entry scores are masked in dark gray. If protein structure is available, distance in angstroms to the closest antibody residue is shown.

m102.4 Antibody Escape

HENV-117 Antibody Escape

HENV-26 Antibody Escape

HENV-103 Antibody Escape

HENV-32 Antibody Escape

nAH1.3 Antibody Escape

Heatmaps of Specific RBP Regions ​

TIP

Click arrow in upper right to view full-sized plots

Effects of mutations on cell entry and binding at receptor contact sites

Effects of mutations on cell entry and binding at glycosylation sites ​

Effects of mutations on cell entry and binding at polymorphic Nipah sites ​

Effects of mutations on cell entry, organized by type of the unmutated amino acid residue ​

The effects of mutations organized by the unmutated amino acid type. Strong preference for certain amino acids can be seen in certain regions. For example, portions of the stalk only tolerate hydrophobic residues (see sites 101-160 below).

Notebooks ​

Heatmap notebook

Built by Brendan Larsen and Jesse Bloom

- + \ No newline at end of file diff --git a/docs/.vitepress/dist/htmls/E2_binding_heatmap.html b/docs/.vitepress/dist/htmls/E2_binding_heatmap.html index 166ef9d3..545eead2 100644 --- a/docs/.vitepress/dist/htmls/E2_binding_heatmap.html +++ b/docs/.vitepress/dist/htmls/E2_binding_heatmap.html @@ -2,43 +2,44 @@ + #vis.vega-embed { + width: 100%; + display: flex; + display: flex; /* Enables Flexbox for this element */ + justify-content: center; /* Centers children horizontally */ + align-items: center; /* Centers children vertically */ + flex-direction: column; /* Organizes children in a column */ + font-size:30px; + transition: color 0.3s ease-in-out, transform 0.3s ease-in-out; + animation: fadeIn 2s ease-out; + } + @keyframes fadeIn { + from {opacity: 0;} + to {opacity: 1;} + } + + #vis.vega-embed details, + #vis.vega-embed details summary { + cursor: pointer; + font-weight: bold; + color: #333; + border-radius: 5px; + margin-bottom: 5px; + } + + diff --git a/docs/.vitepress/dist/htmls/E2_entry_heatmap.html b/docs/.vitepress/dist/htmls/E2_entry_heatmap.html index 7f8eedde..82fc1c98 100644 --- a/docs/.vitepress/dist/htmls/E2_entry_heatmap.html +++ b/docs/.vitepress/dist/htmls/E2_entry_heatmap.html @@ -3,43 +3,43 @@ + #vis.vega-embed { + width: 100%; + display: flex; + display: flex; /* Enables Flexbox for this element */ + justify-content: center; /* Centers children horizontally */ + align-items: center; /* Centers children vertically */ + flex-direction: column; /* Organizes children in a column */ + font-size:30px; + transition: color 0.3s ease-in-out, transform 0.3s ease-in-out; + animation: fadeIn 2s ease-out; + } + @keyframes fadeIn { + from {opacity: 0;} + to {opacity: 1;} + } + + #vis.vega-embed details, + #vis.vega-embed details summary { + cursor: pointer; + font-weight: bold; + color: #333; + border-radius: 5px; + margin-bottom: 5px; + } + + diff --git a/docs/.vitepress/dist/htmls/E3_binding_heatmap.html b/docs/.vitepress/dist/htmls/E3_binding_heatmap.html index 2de0e719..884c98e1 100644 --- a/docs/.vitepress/dist/htmls/E3_binding_heatmap.html +++ b/docs/.vitepress/dist/htmls/E3_binding_heatmap.html @@ -2,43 +2,44 @@ + #vis.vega-embed { + width: 100%; + display: flex; + display: flex; /* Enables Flexbox for this element */ + justify-content: center; /* Centers children horizontally */ + align-items: center; /* Centers children vertically */ + flex-direction: column; /* Organizes children in a column */ + font-size:30px; + transition: color 0.3s ease-in-out, transform 0.3s ease-in-out; + animation: fadeIn 2s ease-out; + } + @keyframes fadeIn { + from {opacity: 0;} + to {opacity: 1;} + } + + #vis.vega-embed details, + #vis.vega-embed details summary { + cursor: pointer; + font-weight: bold; + color: #333; + border-radius: 5px; + margin-bottom: 5px; + } + + diff --git a/docs/.vitepress/dist/htmls/E3_entry_heatmap.html b/docs/.vitepress/dist/htmls/E3_entry_heatmap.html index dd417113..a03b13c3 100644 --- a/docs/.vitepress/dist/htmls/E3_entry_heatmap.html +++ b/docs/.vitepress/dist/htmls/E3_entry_heatmap.html @@ -2,43 +2,44 @@ + #vis.vega-embed { + width: 100%; + display: flex; + display: flex; /* Enables Flexbox for this element */ + justify-content: center; /* Centers children horizontally */ + align-items: center; /* Centers children vertically */ + flex-direction: column; /* Organizes children in a column */ + font-size:30px; + transition: color 0.3s ease-in-out, transform 0.3s ease-in-out; + animation: fadeIn 2s ease-out; + } + @keyframes fadeIn { + from {opacity: 0;} + to {opacity: 1;} + } + + #vis.vega-embed details, + #vis.vega-embed details summary { + cursor: pointer; + font-weight: bold; + color: #333; + border-radius: 5px; + margin-bottom: 5px; + } + + diff --git a/docs/.vitepress/dist/index.html b/docs/.vitepress/dist/index.html index eec8dbef..172bec97 100644 --- a/docs/.vitepress/dist/index.html +++ b/docs/.vitepress/dist/index.html @@ -18,7 +18,7 @@
Nipah RBP DMS

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Nipah RBP DMS

Collection of data, figures, and information for the Nipah virus receptor binding protein deep mutational scanning project

Pipeline information and data processing

Analysis of Pacbio and Illumina sequencing data produced from deep mutational scanning experiments

Cell entry

Analysis of functional selections for assessing how RBP mutations impact cell entry

Receptor binding

Analysis of soluble receptor selections for measuring how mutations affect binding to host receptors

Antibody escape

Analysis of antibody neutralization data for finding sites of escape in RBP

Heatmaps

Links to heatmaps showing effects of mutations on cell entry, receptor binding, and antibody escape

Interactive figures

Explore DMS data on Nipah RBP with interactive figures

About ​

This website contains links and information for the Nipah virus receptor binding protein deep mutational scanning project. Look through Jupyter notebooks used in analyses, or explore interactive charts. To view more information on the code, click on the GitHub logo in upper right. Interactive charts made with Altair. Embedding of Altair plots was done with custom javascript code from dms-vep. Work done in Bloom Lab, part of Fred Hutch Cancer Center.

All experiments were performed with non-replicative lentiviral-based pseudoviruses. Ephrin-B2 and Ephrin-B3 orthologs from the bat species Pteropus alecto were used for cell entry and receptor binding assays.

Built by Brendan Larsen and Jesse Bloom

- + \ No newline at end of file diff --git a/docs/.vitepress/dist/interactive.html b/docs/.vitepress/dist/interactive.html index 00263188..4921ac44 100644 --- a/docs/.vitepress/dist/interactive.html +++ b/docs/.vitepress/dist/interactive.html @@ -18,7 +18,7 @@
Nipah RBP DMS

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Interactive Figures ​

Explore Nipah virus RBP deep mutational scanning data with interactive charts.

To explore heatmaps, click here

TIP

Click white square in the upper right of each plot to view full-sized versions.

Cell Entry ​


Correlations ​

Correlations by Site ​


Notebooks ​

Link to notebooks showing how interactive figures were made:

Interactive figures notebook

Built by Brendan Larsen and Jesse Bloom

- + \ No newline at end of file diff --git a/docs/.vitepress/dist/notebooks/analyze_escape_data.html b/docs/.vitepress/dist/notebooks/analyze_escape_data.html index 718c9ce7..1c935381 100644 --- a/docs/.vitepress/dist/notebooks/analyze_escape_data.html +++ b/docs/.vitepress/dist/notebooks/analyze_escape_data.html @@ -7524,7 +7524,7 @@

analyze_escape_data.ipynb + @@ -8230,23 +8230,23 @@

@@ -12194,23 +12207,23 @@

Now make for all contact sites @@ -12273,7 +12286,7 @@

Make correlat - + + @@ -12724,23 +12847,23 @@

Make correlat @@ -12794,23 +12917,23 @@

Make correlat @@ -12864,23 +12987,23 @@

Make correlat @@ -12948,7 +13071,7 @@

Plot correlations be