Mutation Edgotype Drives Fitness Effect in Human.

ABSTRACT: Missense mutations are known to perturb protein-protein interaction networks (known as interactome networks) in different ways. However, it remains unknown how different interactome perturbation patterns ("edgotypes") impact organismal fitness. Here, we estimate the fitness effect of missense mutations with different interactome perturbation patterns in human, by calculating the fractions of neutral and deleterious mutations that do not disrupt PPIs ("quasi-wild-type"), or disrupt PPIs either by disrupting the binding interface ("edgetic") or by disrupting overall protein stability ("quasi-null"). We first map pathogenic mutations and common non-pathogenic mutations onto homology-based three-dimensional structural models of proteins and protein-protein interactions in human. Next, we perfo

SUBMITTER: Ghadie M 

PROVIDER: S-EPMC9581054 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature