Linking pharmgkb to phenotype studies and animal models of disease for drug repurposing

Robert Hoehndorf*, Anika Oellrich, Dietrich Rebholz-Schuhmann, Paul N. Schofield, Georgios V. Gkoutos

*Corresponding author for this work

Research output: Contribution to journalConference articlepeer-review

16 Scopus citations

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 signedrank 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.

Original languageEnglish (US)
Pages (from-to)388-399
Number of pages12
JournalPacific Symposium on Biocomputing
StatePublished - Jan 1 2012
Event17th Pacific Symposium on Biocomputing, PSB 2012 - Kohala Coast, United States
Duration: Jan 3 2012Jan 7 2012

Keywords

  • Animal models
  • Drug repurposing
  • Ontology
  • Pharmacogenetics
  • Phenotype

ASJC Scopus subject areas

  • Medicine(all)

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