Systems approaches to link tissue-specific expression to disease

描述（由申请人提供）：本研究计划的长期目标是使用GTEx项目的数据，提供工具、分析和框架，以建立组织特异性表达与复杂疾病的遗传原因之间的联系。该建议分为四个目标：(i)将线性eQTL模型的发展扩展到RNA-Seq外显子水平和总读计数（TReC）映射的分析，并包括eQTL指纹和质量加权回归；（ii）为多组织eQTL分析开发新的统计方法；（iii）在多个组织中识别等位基因特异性和同种异型特异性的eQTL， （iv）通过将常见和组织特异性的eQTL发现与疾病特异性数据库相交叉，全面评估GTEx与疾病的关系。这项建议将扩展或发展一些工具，这些工具将是全球贸易系统成功的关键。当前版本的工具要么速度慢，要么不适合多组织环境。我们将把这些工具应用于GTEx，并与其他GTEx分析小组密切合作，这些工具将对eQTL分析社区具有广泛的实用性。

DESCRIPTION (provided by applicant): The long-term objective of this research proposal is to provide the tools, analysis, and a framework to establish the connection between tissue-specific expression and heritable causes of complex disease, using data from the GTEx Project. The proposal is divided into four Aims: (i) To extend our development of linear eQTL models to the analysis of RNA-Seq exon-level and total read-count (TReC) mapping, and to include eQTL fingerprinting and quality-weighted regression; (ii) to develop new statistical methods for multi-tissue eQTL analysis; (iii) to identify allele-specific and isoform-specific eQTLs across multiple tissues, and (iv) to comprehensively evaluate GTEx relationships with disease by intersecting common and tissue-specific eQTL findings with disease-specific databases. This proposal will extend or develop several tools that will be key to the success of GTEx. Current versions of the tools are either slow or not designed for the multi-tissue setting. We will apply these tools to GTEx and work closely with other GTEx analysis groups, and the tools will have wide utility for the eQTL analysis community.