Evaluating sequence and structural similarity metrics for predicting shared paralog functions.

ABSTRACT: Gene duplication is the primary source of new genes, resulting in most genes having identifiable paralogs. Over time, paralog pairs may diverge in some respects but many retain the ability to perform the same functional role. Protein sequence identity is often used as a proxy for functional similarity and can predict shared functions between paralogs as revealed by synthetic lethal experiments. However, the advent of alternative protein representations, including embeddings from protein language models (PLMs) and predicted structures from AlphaFold, raises the possibility that alternative similarity metrics could better capture functional similarity between paralogs. Here, using two species (budding yeast and human) and two different definitions of shared functionality (shared protein-prot

SUBMITTER: Dennler O 

PROVIDER: S-EPMC12034104 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature