ntranoslab/diff-tol

Supplementary data for "Uncovering differential tolerance to deletions versus substitutions with a deep protein language model"

This repo contains scripts and datasets needed to replicate the figures in "Uncovering differential tolerance to deletions versus substitutions with a deep protein language model." All code in code/ is organized by figure section.

Data Directory

The repo is generally self-contained, although a few additional datasets must be downloaded by the user, depending on which figures are to be replicated:

• All AlphaFold .pdb files for human proteins, via https://alphafold.ebi.ac.uk/download.
• ESM1b substitution (LLR) effects, via https://huggingface.co/spaces/ntranoslab/esm_variants/blob/main/ALL_hum_isoforms_ESM1b_LLR.zip.

Supplementary data files

• data/all_helix_llr.csv.gz All substitution effects (LLR) within helices.
• data/all_w2g_llr.csv.gz All W -> G substitution effects (LLR).
• data/esm_ins_sub_pllr.csv.gz Insertion and substitution effects, measured via PLLR, for 1,632 structurall diverse proteins.
• data/gnomad_del_sub_merge_AF.csv.gz Allele frequencies for all sites in gnomAD containing both a single in-frame amino acid deletion and a substitution.
• data/tsuboyama_ddg.csv Processed ddG measurements from Tsuboyama et al. https://doi.org/10.1038/s41586-023-06328-6
• data/tsuboyama_esmfold_plddt.csv Average ESMFold pLDDT per structure in Tsuboyama et al. containing a D-S+ site, and deletions and substitutions on these sites.
• data/uniprot_domains.tsv.gz All annotated UniProt domains for human canonical transcripts.
• data/uniprot_sequences_all.tsv.gz All sequences for all human proteins in UniProt.

Code Directory

Find scripts to replicate all main text figures.