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Evaluation of GWAS hits as prospect targets for drug therapy: the CAD/MI case

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Genome-wide association studies (GWAS) have identified so far thousands of loci associated hundreds of traits. Only a few of these loci are currently targets of on-market medications. Using coronary artery disease (CAD) and myocardial infarction (MI) hits as our study case, we systematically evaluated these risk loci for their druggability potential, assessing their correlation with other phenotypes, known and predicted interactions with drugs and potential side effects, integrating multiple sources of information. To identify drugs suitable for repurposing and to identify new targets for drugs, we created two unique pipelines integrating currently available public data. The first is the drug repurposing pipeline: it uses publicly available GWAS results to predict relevant side effects of targeting CAD /MI loci, identifies drug-gene interactions and filters most suitable candidates for repurposing among drugs existing in the market. The second pipeline is for prioritization of gene product targets: it calculates a druggability score to estimate how dock-able the pockets of CAD /MI associated gene products are, uses GWAS results to predict side effects, excludes loci with widespread cross-tissue expression to avoid housekeeping and vital genes and ranked the remaining gene products. The advantages and caveats of these approaches will be presented and discussed, along with future directions.

Dr. Vinicius Tragante is a researcher at University Medical Center Utrecht (The Netherlands), where he also obtained his PhD in Bioinformatics in the De Bakker and Asselbergs labs. Currently he is working with GWAS analyses and post-GWAS functional assessment and druggability.

This talk is part of the Cambridge Cardiovascular Seminar Series series.

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