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Deep mutational scanning of SARS-CoV-2 XBB.1.5 spike to map escape from primary infection infants

Study by Bernadeta Dadonaite and Jesse Bloom in collaboration with Mary Staat's group. See Dadonaite et al (2025) for details on the study.

This repo contains the data and code for pseudovirus deep mutational scanning of XBB.1.5 spike with respect to escape from sera from infants first exposed to XBB variants. The library used here and some of the comparator adult data are from the previously published study Dadonaite et al (2024).

For documentation of the analysis, see https://dms-vep.github.io/SARS-CoV-2_XBB.1.5_spike_DMS_infant_sera/

Organization of this repo

dms-vep-pipeline-3 submodule

Most of the analysis is done by the dms-vep-pipeline-3, which was added as a git submodule to this pipeline via:

git submodule add https://github.com/dms-vep/dms-vep-pipeline-3

This added the file .gitmodules and the submodule dms-vep-pipeline-3, which was then committed to the repo. Note that if you want a specific commit or tag of dms-vep-pipeline-3 or to update to a new commit, follow the steps here, basically:

cd dms-vep-pipeline-3
git checkout <commit>

and then cd ../ back to the top-level directory, and add and commit the updated dms-vep-pipeline-3 submodule. You can also make changes to the dms-vep-pipeline-3 that you commit back to that repo.

Configuration and running the pipeline

The configuration for the pipeline is in config.yaml and the files in ./data/ referenced therein. To run the pipeline, do:

snakemake -j 8 --use-conda -s dms-vep-pipeline-3/Snakefile

Note that the pipeline is currently configured to start by processing the FASTQ files from the paths where they are stored on the Hutch server as specified in data/barcode_runs.csv. To instead simply run the pipeline from the precomputed barcode counts files stored in this repo, set use_precomputed_barcode_counts: true in config.yaml.

To run on the Hutch cluster via slurm, you can run the file run_Hutch_cluster.bash:

sbatch -c 8 run_Hutch_cluster.bash

Results and documentation

The results of running the pipeline are placed in ./results/. Only some of these results are tracked to save space (see .gitignore).

The pipeline builds HTML documentation for the pipeline in ./docs/, which is rendered via GitHub Pages at https://dms-vep.github.io/SARS-CoV-2_XBB.1.5_spike_DMS_infant_sera.

Analysis of validation experiments for DMS is in ./validation_notebooks/