Poster Presentation Melbourne Protein Group Student Symposium 2013

Identification of novel therapeutics for complex diseases from genome-wide association data (#32)

Mani Grover 1 , Kaavya Mohanasundaram 1 , Sara Ballouz 2 , R A George 3 , Tamsyn Crowley 1 , Craig Sherman 1 , Merridee Wouters 1
  1. Deakin University, Geelong Waurn Pond, VIC, Australia
  2. Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, United States.
  3. Victor Chang Cardiac Research Institute, Darlinghurst , NSW, Australia

Candidate gene prediction systems identify genes likely to be of functional relevance to a phenotype from associated genetic loci. Gentrepid, a human candidate gene discovery platform, utilizes two algorithms- Common Module Profiling and Common Pathway Scanning - to prioritize candidate genes for human inherited disorders. Recently, several protocols were developed to apply Gentrepid to the analysis of data from Genome Wide Association Studies (GWAS) using the Wellcome Trust Case Control Consortium (WTCCC) data set on seven complex diseases as an example (Ballouz et al, 2011).We are integrating drug databases now to enable researchers to immediately associate potential therapeutics with candidate genes. In this work presented here, we associated drugs with seven WTCCC phenotypes. For instance, Gentrepid predicted Peroxisome proliferator activated receptor delta (PPARD) as a candidate gene for Type II diabetes. Using the reference drug databases, we identified a dozen drugs that target PPARD. Drug Bank (Wishart et al, 2006) suggested 10 drugs used to treat lipid and glucose metabolic diseases, the Therapeutic Target Database (TTD) (Chen et al, 2002) indicated two drugs currently used to treat obesity and hyperlipidemia, and Pharm-GKB database (Hernandez et al, 2008) suggested two drugs used to treat prostatic neoplasms. For Carbohydrate (chondroitin 6) sulfotranferase 3 (CHST3), another Gentrepid candidate gene for Type II diabetes, Pharm-GKB suggested the same two drugs to treat prostatic neoplasms as identified for the PPARD gene. Thus, these drugs can be immediately utilized in further laboratory studies and in phase III clinical trials.

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