Linking PharmGKB to Phenotype Studies and Animal Models of Disease for Drug Repurposing
Linking PharmGKB to Phenotype Studies and Animal Models of Disease for Drug Repurposing
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DOI：
10.1142/9789814366496_0038
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发表时间：
2011-12
影响因子：
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通讯作者：
R. Hoehndorf;A. Oellrich;Dietrich Rebholz-Schuhmann;P. Schofield;G. Gkoutos
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文献类型：
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作者：
R. Hoehndorf;A. Oellrich;Dietrich Rebholz-Schuhmann;P. Schofield;G. Gkoutos
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.
