Fine-tuning the ESM2 protein language model to understand the functional impact of missense variants

Fuente: arXiv
Saved in:
Bibliographic Details
Main Authors: Saadat, Ali, Fellay, Jacques
Format: Preprint
Published: 2024
Subjects:
Online Access:
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1866908383687213056
author Saadat, Ali
Fellay, Jacques
author_facet Saadat, Ali
Fellay, Jacques
contents Elucidating the functional effect of missense variants is of crucial importance, yet challenging. To understand the impact of such variants, we fine-tuned the ESM2 protein language model to classify 20 protein features at amino acid resolution. We used the resulting models to: 1) identify protein features that are enriched in either pathogenic or benign missense variants, 2) compare the characteristics of proteins with reference or alternate alleles to understand how missense variants affect protein functionality. We show that our model can be used to reclassify some variants of unknown significance. We also demonstrate the usage of our models for understanding the potential effect of variants on protein features.
format Preprint
id arxiv_https___arxiv_org_abs_2410_10919
institution arXiv
publishDate 2024
record_format arxiv
spellingShingle Fine-tuning the ESM2 protein language model to understand the functional impact of missense variants
Saadat, Ali
Fellay, Jacques
Quantitative Methods
Genomics
Elucidating the functional effect of missense variants is of crucial importance, yet challenging. To understand the impact of such variants, we fine-tuned the ESM2 protein language model to classify 20 protein features at amino acid resolution. We used the resulting models to: 1) identify protein features that are enriched in either pathogenic or benign missense variants, 2) compare the characteristics of proteins with reference or alternate alleles to understand how missense variants affect protein functionality. We show that our model can be used to reclassify some variants of unknown significance. We also demonstrate the usage of our models for understanding the potential effect of variants on protein features.
title Fine-tuning the ESM2 protein language model to understand the functional impact of missense variants
topic Quantitative Methods
Genomics
url https://arxiv.org/abs/2410.10919