title: Linking PharmGKB to phenotype studies and animal models of disease for drug repurposing.
abstract: The investigation of phenotypes in model organisms has the potential to reveal the molecular mechanisms underlying disease. The large-scale comparative analysis of phenotypes across species can reveal novel associations between genotypes and diseases. We use the PhenomeNET network of phenotypic similarity to suggest genotype-disease association, combine them with drug-gene associations available from the PharmGKB database, and infer novel associations between drugs and diseases. We evaluate and quantify our results based on our method's capability to reproduce known drug-disease associations. We find and discuss evidence that levonorgestrel, tretinoin and estradiol are associated with cystic fibrosis (p < 2.65 · 10(-6), p < 0.002 and p < 0.031, Wilcoxon signed-rank test, Bonferroni correction) and that ibuprofen may be active in chronic lymphocytic leukemia (p < 2.63 · 10(-23), Wilcoxon signed-rank test, Bonferroni correction). To enable access to our results, we implement a web server and make our raw data freely available. Our results are the first steps in implementing an integrated system for the analysis and prediction of drug-disease associations for rare and orphan diseases for which the molecular basis is not known.
authors.affiliation: Department of Genetics, University of Cambridge, Cambridge, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Hoehndorf
authors.forename: Anika
authors.initials: A
authors.lastname: Oellrich
authors.forename: Dietrich
authors.initials: D
authors.lastname: Rebholz-Schuhmann
authors.forename: Paul N
authors.initials: PN
authors.lastname: Schofield
authors.forename: Georgios V
authors.initials: GV
authors.lastname: Gkoutos
mesh_terms: D000818:Animals; D019295:Computational Biology; D016208:Databases, Factual; D030541:Databases, Genetic; D004194:Disease / Q000235:genetics; D004195:Disease Models, Animal; D055808:Drug Discovery / Q000706:statistics & numerical data; D006801:Humans; D051188:Knowledge Bases; D010597:Pharmacogenetics / Q000706:statistics & numerical data*; D010641:Phenotype