Generation of Ethanol Response Gene Resource by Large-Scale Data Integration

描述（由申请人提供）：在过去的10-15年中，在人类和动物模型中，乙醇相关特征的研究取得了快速进展，包括酒精中毒和对乙醇的行为反应。精细的遗传策略和高通量分子技术，如大规模基因分型和DNA微阵列，已经确定了相对大量的染色体位置和候选基因，这些基因与酗酒和乙醇反应行为的遗传风险有关。目前，整合和使综合的丰富的结果易于获取和解释，对研究人员提出了重大挑战。在这个应用中，我们提出构建这样一个独特而重要的乙醇反应基因资源（ERGR）。我们将首先收集和整理所有乙醇反应基因的可用数据集，包括由VCU小组生成的和公开可用的数据集。这些内部和外部数据的例子包括人类连锁扫描和关联研究、小鼠乙醇QTL、微阵列数据、高通量文献检索和其他生物（如大鼠、苍蝇、蠕虫）中的候选基因。收集到的数据将通过数据管理系统进行整合，并由计算机程序定期更新。易感基因及其特征的鉴定将进行许多分析，包括比较基因组学、基因网络、基因本体术语和基因表达分析。我们还将开发用于候选基因优先排序的评分算法，并实现用于定制基因优先排序的工具。最后，我们将设计并实现一个用户友好的基于web的平台。该平台将提供(1)同时访问收集和注释的数据以及某些公共基因组数据库；(2)统计分析和数据展示工具。总体目标是为NIAAA研究界提供一个全面的乙醇反应基因资源，促进对酒精中毒中单个基因作用机制的理解，并确定酒精中毒新干预措施的潜在靶点。公共卫生相关性：拟议的项目将收集、整理和分析乙醇反应基因的所有可用数据集，并优先考虑未来研究的候选基因。将为NIAAA研究团体构建一个用户友好的基于web的乙醇反应基因数据库系统。

DESCRIPTION (provided by applicant): Over the last 10-15 years rapid progress has been made in the study of ethanol related traits including alcoholism and behavioral responses to ethanol in both humans and animal models. Refined genetic strategies and high-throughput molecular technologies such as large-scale genotyping and DNA microarrays have identified a relatively large number of chromosomal locations and candidate genes contributing to the genetic risk for alcoholism and ethanol response behaviors. At present, integrating and making the combined wealth of results easily accessible and interpretable presents significant challenges for researchers. In this application, we propose to construct such a unique and important ethanol response gene resource (ERGR). We will first collect and curate all the available data sets for ethanol response genes including those generated by the groups at VCU and publicly available. Examples of these internal and external data include human linkage scan and association studies, mouse ethanol QTL, microarray data, high throughput literature searches, and candidate genes in other organisms (e.g. rat, fly, worm). The collected data will be integrated via a data management system and updated routinely by computer programs. Many analyses will be performed for the identification of susceptibility genes and their features, including comparative genomics, gene network, Gene Ontology term, and gene expression analyses. We will also develop scoring algorithms for prioritizing candidate genes and implement tools for customization of gene prioritization. Finally, we will design and implement a user-friendly web-based platform. This platform will provide (1) simultaneous access to the data collected and annotated and to certain public genomic databases and (2) tools for statistical analysis and data presentation. The overall goal is to provide a comprehensive ethanol response gene resource to NIAAA research community and to facilitate understanding the mechanism(s) of action for individual genes in alcoholism and identify potential targets for novel new interventions in alcoholism. Public Health Relevance: The proposed project will collect, curate, and analyze all the available data sets for ethanol response genes and prioritize the candidate genes for future investigation. A user-friendly web-based ethanol response gene database system will be constructed for NIAAA research community.