A Genome-wide Functional Signature Ontology Map and Applications to Natural Product Mechanism of Action Discovery.

ABSTRACT: Gene expression signature-based inference of functional connectivity within and between genetic perturbations, chemical perturbations, and disease status can lead to the development of actionable hypotheses for gene function, chemical modes of action, and disease treatment strategies. Here, we report a FuSiOn-based genome-wide integration of hypomorphic cellular phenotypes that enables functional annotation of gene network topology, assignment of mechanistic hypotheses to genes of unknown function, and detection of cooperativity among cell regulatory systems. Dovetailing genetic perturbation data with chemical perturbation phenotypes allowed simultaneous generation of mechanism of action hypotheses for thousands of uncharacterized natural products fractions (NPFs). The predicted mechanism

SUBMITTER: McMillan EA 

PROVIDER: S-EPMC9161285 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature