A Novel Drug-Mouse Phenotypic Similarity Method Detects Molecular Determinants of Drug Effects
Fig 1
Schematic representation of the phenotypic similarity approach and validation of the method.
a) Illustration of the phenotypic similarity approach that corrects for the polypharmacological property of drugs. A drug may affect multiple targets leading to more side effects than the one resulting from single gene perturbations in mice [23]. We therefore utilized only a subset of 20 side effects (see S2 and S3 Figs for cutoff evaluation) that are most similar to the mouse phenotypic traits to assess the similarity between a mouse gene and a drug. b) We evaluated our method with benchmark sets of direct and indirect human drug-target relationships, functional associations mediated through drug targets via protein-protein interactions, gene-drug pairs involved in pharmacogenetic associations and causal connections between human genes and side effects.