Informatics Core - Pharmacogenomics of Statin Therapy (POST)

信息学核心：项目总结 他汀类药物治疗药物基因组学(POST)中心开发了三个项目来发现和 验证与他汀类药物效应相关的新的基因组标记(基因、转录本、代谢物或SNPs)。至 促进科学进步并协同中心，使集体整体大于 这些部分，我们已经开发了一个信息学核心来整合将收集的大量数据，提供 分析项目的专业知识，并开发新方法来集成和可视化这三个项目中的数据 项目包括人类淋巴母细胞系的转录和代谢组学研究，遗传和 在小鼠模型中的功能研究，以及在大人口样本中的广泛的遗传流行病学研究。 信息学核心的一个关键功能是整合从这些不同但 互为补充的平台，从而充分利用每个数据集来最大限度地了解因素 他汀类药物反应的潜在变异。信息学核心的总体目标是促进最大限度地 对三个项目的数据和结果进行分析和协调。此核心将作为 在三个员额项目之间共享数据的中央枢纽，以及作为 结合三个项目的数据/结果提取有关他汀类药物反应的新知识，但尚未实现 仅从一个项目。我们将通过以下三个具体目标实现这些目标：目标1)集合 并集成来自项目1-3的数据集，以最大限度地提高三个项目之间的协作。目标2)发展 并应用生物信息学工具将不同实验策略(项目1-3)的结果整合到 确定与他汀类药物疗效或不良反应相关的基因、代谢物、网络和/或DNA变体 使用机器学习和强大的生物学注释。目标3)开发交互式数据可视化 综合不同实验策略的结果的工具(来自项目1-3)。除了这些目标外， CORE还将与个别项目调查人员密切合作，执行更高级别的统计分析，以 服务于每个项目的特定需求。通过这些活动，信息学核心不仅将帮助 确定可用于制定他汀类药物精确医学指南的标记物 治疗，但也将开发新的统计工具，可普遍应用于药物基因组学 研究。

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.