Systems approaches to link tissue-specific expression to disease

描述(由申请人提供)：这项研究提案的长期目标是提供工具、分析和框架，以利用GTEx项目的数据，在复杂疾病的组织特异性表达和可遗传原因之间建立联系。该建议分为四个目标：(I)将我们开发的线性eQTL模型扩展到RNA-Seq外显子水平和总读取计数(TREC)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)在多个组织中识别特定等位基因和特定异构体的eQTL；以及(Iv)通过将常见的和组织特定的eQTL结果与疾病特定的数据库交叉，来综合评估GTEx与疾病的关系。这项提议将扩展或开发几种工具，这些工具将是GTEx成功的关键。当前版本的工具要么速度慢，要么不是为多组织设置而设计的。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价值。

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.