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Summary

Analysis run by Snakefile using this config file. See the README in the top directory for details.

Here is the DAG of the computational workflow: dag.svg

Here is the Markdown output of each Jupyter notebook in the workflow:

  1. Process PacBio CCSs.

  2. Build variants from CCSs. Creates a codon variant table linking barcodes to the mutations in the variants.

  3. Count variants by barcode. Creates a variant counts file giving counts of each barcoded variant in each condition.

  4. QC analysis of sequencing counts.

  5. Computation of ACE2-binding KD. Creates files giving the ACE2-binding of each barcoded variant of SARS-CoV-2 RBD and of the homologs.

  6. Computation of expression mean fluorescence. Creates files giving the expression of each barcoded variant of SARS-CoV-2 RBD and of the homologs.

  7. Global epistasis decomposition of binding effects.

  8. Global epistasis decomposition of expression effects.

  9. Calculation of final single mutant effects on binding and expression. Creates files giving the estimated expression and ACE2-binding of single mutants to SARS-CoV-2 RBD and the homologs.

  10. Structure-function analysis of mutational effects.

  11. Logo plots of mutational effects. Also creates input files for dms-view of RBD and spike, the visualizations of which can be seen here.

  12. Mutational constraint within RBD antibody epitopes

  13. RBD variation across the sarbecovirus clade

  14. RBD variation in circulating SARS-CoV-2 isolates.

  15. Make interactive heat map. Creates this heatmap.