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.

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.

• data/tsuboyama_ddg_esm_scores.csv.gz Tsuboyama sites with ESM-predicted deletion and substitution tolerance.
• data/tsuboyama_ddg_processed.csv.gz Processed ddG measurements from Tsuboyama et al. https://doi.org/10.1038/s41586-023-06328-6
• data/tsuboyama_2mkx_i36.csv Raw, disaggregated stability change measurements at position I36 in domain 2MKX from Tsuboyama et al.
• data/pg_predictions_with_esm.csv.gz Experimental deletion datasets curated from https://proteingym.org/ with VEP scores, including ESM.
• data/esm_ins_sub_pllr.csv.gz Insertion and substitution effects, measured via PLLR, for 1,632 structurall diverse proteins.
• 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.
• data/pdb_data.csv.gz Contact number, rSASA, binding site data computd from the .pdb file or extracted from UniProt.

Find scripts to replicate all main text and supplementary figures.