3D structural human interactome reveals proteome-wide perturbations by disease mutations.

ABSTRACT: Human genome sequencing studies have identified numerous loci associated with complex diseases. However, translating human genetic and genomic findings to disease pathobiology and therapeutic discovery remains a major challenge at multiscale interactome network levels. Here, we present a deep-learning-based ensemble framework, termed PIONEER (Protein-protein InteractiOn iNtErfacE pRediction), that accurately predicts protein binding partner-specific interfaces for all protein interactions in humans and seven other common model organisms. We demonstrate that PIONEER outperforms existing state-of-the-art methods. We further systematically validated PIONEER predictions experimentally through generating 2,395 mutations and testing their impact o

SUBMITTER: Xiong D 

PROVIDER: S-EPMC10168245 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature