Unified inference of missense variant effects and gene constraints in the human genome.

ABSTRACT: A challenge in medical genomics is to identify variants and genes associated with severe genetic disorders. Based on the premise that severe, early-onset disorders often result in a reduction of evolutionary fitness, several statistical methods have been developed to predict pathogenic variants or constrained genes based on the signatures of negative selection in human populations. However, we currently lack a statistical framework to jointly predict deleterious variants and constrained genes from both variant-level features and gene-level selective constraints. Here we present such a unified approach, UNEECON, based on deep learning and population genetics. UNEECON treats the contributions of variant-level features and gene-level constraints as a variant-level fixed effect and a gene-leve

SUBMITTER: Huang YF 

PROVIDER: S-EPMC7384676 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature