A Novel Drug-Mouse Phenotypic Similarity Method Detects Molecular Determinants of Drug Effects.

ABSTRACT: The molecular mechanisms that translate drug treatment into beneficial and unwanted effects are largely unknown. We present here a novel approach to detect gene-drug and gene-side effect associations based on the phenotypic similarity of drugs and single gene perturbations in mice that account for the polypharmacological property of drugs. We scored the phenotypic similarity of human side effect profiles of 1,667 small molecules and biologicals to profiles of phenotypic traits of 5,384 mouse genes. The benchmarking with known relationships revealed a strong enrichment of physical and indirect drug-target connections, causative drug target-side effect links as well as gene-drug links involved in pharmacogenetic associations among phenotypically similar gene-drug pairs. The validation by in

SUBMITTER: Prinz J 

PROVIDER: S-EPMC5038975 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature