Elucidating Compound Mechanism of Action by Network Perturbation Analysis.

ABSTRACT: Genome-wide identification of the mechanism of action (MoA) of small-molecule compounds characterizing their targets, effectors, and activity modulators represents a highly relevant yet elusive goal, with critical implications for assessment of compound efficacy and toxicity. Current approaches are labor intensive and mostly limited to elucidating high-affinity binding target proteins. We introduce a regulatory network-based approach that elucidates genome-wide MoA proteins based on the assessment of the global dysregulation of their molecular interactions following compound perturbation. Analysis of cellular perturbation profiles identified established MoA proteins for 70% of the tested compounds and elucidated novel proteins that were experimentally validated. Finally, unknown-MoA compou

SUBMITTER: Woo JH 

PROVIDER: S-EPMC4506491 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature