Informatics Core - Pharmacogenomics of Statin Therapy (POST)

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INFORMATICS CORE: PROJECT SUMMARY The Pharmacogenomics of Statin Therapy (POST) Center has developed three projects to discover and validate novel genomic markers (genes, transcripts, metabolites or SNPs) associated with statin effects. To facilitate scientific progress and synergize the Center such that the collective whole is greater than the sum of the parts, we have developed an Informatics Core to integrate the extensive data that will be collected, provide analysis expertise to the projects, and develop novel methods to integrate and visualize data across the three projects which include transcriptomic and metabolomic studies in human lymphoblastoid cell lines, genetic and functional studies in murine models, and extensive genetic epidemiology studies in a large population sample. A key function of the Informatics Core is to integrate information obtained across these diverse yet complementary platforms, thus fully leveraging each dataset to maximize our understanding of the factors underlying variation in statin response. The overall objective of the Informatics Core is to facilitate the maximal level of analysis and coordination of data and results across the three projects. This Core will function as the central hub for data sharing across the three POST projects, as well as functioning as `The Integrator' for combining the data/results from the three projects to extract new knowledge about statin response, not realized from one project alone. We will achieve these goals through the following three specific aims: Aim 1) Assemble and integrate datasets from Projects 1-3 to maximize collaborations across the three projects. Aim 2) Develop and apply a bioinformatics tool to integrate results from different experimental strategies (from Projects 1-3) to identify genes, metabolites, networks and/or DNA variants associated with statin efficacy or adverse effects using machine learning and powerful biological annotations. Aim 3) Develop an interactive data visualization tool to combine results from different experimental strategies (from Projects 1-3). In addition to these Aims, the Core will also work closely with individual Project investigators to perform higher-order statistical analyses to serve the specific needs of each Project. Through these activities, the Informatics Core will not only aid in the identification of markers that may be used in the development of precision medicine guidelines for statin treatment, but will also develop novel statistical tools that may be generally applied to pharmacogenomics research.