Drug-set enrichment analysis: a novel tool to investigate drug mode of action

• DOI: 10.1093/bioinformatics/btv536
• Publication Date: 2015-09-29T01:59:04Z
• Authors: Francesco Napolitano; Francesco Sirci; Diego Carrella; Diego di Bernardo
• Keywords: Drug action; Mode of Action

Abstract Motivation: Automated screening approaches are able to rapidly identify a set of small molecules inducing desired phenotype from large small-molecule libraries. However, the resulting candidate is usually very diverse pharmacologically, thus little insight on shared mechanism action (MoA) underlying their efficacy can be gained. Results: We introduce computational method (Drug-Set Enrichment Analysis—DSEA) based drug-induced gene expression profiles, which molecular pathways that targeted by most drugs in set. By diluting drug-specific effects unrelated interest, DSEA highlight phenotype-specific pathways, helping formulate hypotheses MoA validated analysing five different drug-sets related well-known pharmacological classes. then applied known partially effective rescuing mutant cystic fibrosis transmembrane conductance regulator (CFTR) function Cystic Fibrosis. Availability and implementation: The implemented as an online web tool publicly available at http://dsea.tigem.it. Contact: [e-mail] Supplementary information: data Bioinformatics online.