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

描述(申请人提供)：在过去的10-15年里，酒精相关特征的研究取得了快速进展，包括在人类和动物模型中的酒精中毒和对酒精的行为反应。改进的遗传策略和高通量的分子技术，如大规模的基因分型和DNA微阵列，已经确定了相对大量的染色体位置和候选基因，导致了酒精中毒和酒精反应行为的遗传风险。目前，整合和使合并的结果财富更容易获得和解释对研究人员来说是一个巨大的挑战。在这一应用中，我们提出构建这样一个独特而重要的乙醇应答基因资源(ERGR)。我们将首先收集和整理乙醇反应基因的所有可用的数据集，包括由VCU的研究小组产生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、高通量文献搜索以及其他生物(例如老鼠、苍蝇、蠕虫)的候选基因。收集的数据将通过数据管理系统整合，并由计算机程序进行例行更新。将进行许多分析来识别易感基因及其特征，包括比较基因组学、基因网络、基因本体论术语和基因表达分析。我们还将开发候选基因优先排序的评分算法，并实现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)对收集和注释的数据以及某些公共基因组数据库的同时访问，以及(2)统计分析和数据呈现的工具。总体目标是向NIAAA研究界提供全面的乙醇反应基因资源，促进了解酒精中毒单个基因的作用机制(S)，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，并为未来的研究确定候选基因的优先顺序。将为NIAAA研究社区构建一个用户友好的基于网络的乙醇响应基因数据库系统。

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.