title: Integrating Clinical Phenotype and Gene Expression Data to Prioritize Novel Drug Uses.
abstract: Drug repositioning has been based largely on genomic signatures of drugs and diseases. One challenge in these efforts lies in connecting the molecular signatures of drugs into clinical responses, including therapeutic and side effects, to the repurpose of drugs. We addressed this challenge by evaluating drug-drug relationships using a phenotypic and molecular-based approach that integrates therapeutic indications, side effects, and gene expression profiles induced by each drug. Using cosine similarity, relationships between 445 drugs were evaluated based on high-dimensional spaces consisting of phenotypic terms of drugs and genomic signatures, respectively. One hundred fifty-one of 445 drugs comprising 450 drug pairs displayed significant similarities in both phenotypic and genomic signatures (P value < 0.05). We also found that similar gene expressions of drugs do indeed yield similar clinical phenotypes. We generated similarity matrixes of drugs using the expression profiles they induce in a cell line and phenotypic effects.
authors.affiliation: Institute for Computational Health Sciences, School of Medicine, University of California San Francisco, San Francisco, California, USA.|Department of Pediatrics, School of Medicine, University of California - San Francisco, San Francisco, California, USA.
authors.forename: H
authors.initials: H
authors.lastname: Paik
authors.affiliation: Institute for Computational Health Sciences, School of Medicine, University of California San Francisco, San Francisco, California, USA.|Department of Pediatrics, School of Medicine, University of California - San Francisco, San Francisco, California, USA.
authors.forename: B
authors.initials: B
authors.lastname: Chen
authors.affiliation: Institute for Computational Health Sciences, School of Medicine, University of California San Francisco, San Francisco, California, USA.|Department of Pediatrics, School of Medicine, University of California - San Francisco, San Francisco, California, USA.
authors.forename: M
authors.initials: M
authors.lastname: Sirota
authors.affiliation: Institute for Computational Health Sciences, School of Medicine, University of California San Francisco, San Francisco, California, USA.|Department of Pediatrics, School of Medicine, University of California - San Francisco, San Francisco, California, USA.
authors.forename: D
authors.initials: D
authors.lastname: Hadley
authors.affiliation: Institute for Computational Health Sciences, School of Medicine, University of California San Francisco, San Francisco, California, USA.|Department of Pediatrics, School of Medicine, University of California - San Francisco, San Francisco, California, USA.
authors.forename: A J
authors.initials: AJ
authors.lastname: Butte
mesh_terms: D000465:Algorithms; D004347:Drug Interactions; D058492:Drug Repositioning / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D004364:Pharmaceutical Preparations / Q000032:analysis*; D010641:Phenotype; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D004364:Pharmaceutical Preparations