Systems approaches to link tissue-specific expression to disease

描述（由申请人提供）：本研究提案的长期目标是提供工具，分析和框架，以使用GTEx项目的数据建立组织特异性表达与复杂疾病遗传原因之间的联系。本研究的主要目的是：（1）将线性eQTL模型的发展扩展到RNA-Seq外显子水平和总读段计数（TReC）作图分析，包括eQTL指纹分析和质量加权回归分析;（2）发展新的多组织eQTL分析的统计方法;（iii）鉴定跨多个组织的等位基因特异性和同工型特异性eQTL，和（iv）通过将常见和组织特异性eQTL结果与疾病特异性数据库交叉来全面评估GTEx与疾病的关系。该提案将扩展或开发几个工具，这些工具将是GTEx成功的关键。当前版本的工具要么速度慢，要么不适用于多组织设置。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.