MAPGen Knowledge Base (MAPGenKB) and Coordination Center

描述（由申请人提供）：我们建议开发和实施用于心脏、肺、血液和睡眠疾病遗传分析的跨器官机制相关表型联盟（MAPGen）的知识库和协调中心。我们的团队拥有丰富的生物信息学、统计学、计算机科学专业知识，以及心脏、肺和血液疾病方面的临床和生物学专业知识。我们提出该中心的三个主要职能：（1）开发疾病之间相互联系的知识库。我们将系统地识别、整合和分析大量的公共数据（例如NCBI GEO、SRA、dbGap和已发表的论文），以全面描述疾病之间共有的分子机制。我们将建立一个多维疾病连通图，可以通过网络界面交互式访问。利用这个知识库，我们将设计计算方法来识别可用于预测多种疾病的生物标志物，根据潜在的分子机制重新组合疾病，设计预测疾病进展的新方法，并确定新的药物用途。 (2) 为 MAPGen 联盟开发生物信息学基础设施。我们将负责联盟生成的数据的质量控制；我们将对不同 RC 生成的数据以及来自公共领域的数据进行综合分析，以获得对 HLBS 疾病之间共享分子机制的深入见解和基本理解。我们将利用目标 1 中开发的知识库进一步建立 HLBS 与其他疾病之间的联系。我们将与南加州大学的医学联合研究人员以及所有 RC 团队密切合作，开发和验证生物学假设。 (3) 我们将建立一个行政中心来协调各区域委员会的活动，包括协调稿件和其他文件的准备；协调所有委员会的活动；整体研究协调和质量控制；并管理第 3 年和第 4 年额外资金的分配。我们的目标是协同所有 RC 的努力，以实现了解跨器官疾病之间相互关联的遗传机制的目标。相关性（参见说明）：拟议项目将促进跨器官系统常见病理生物学特征和机制的识别和表征，并为心、肺、血液和睡眠障碍的新诊断、预后和治疗策略的合理、基于机制的开发提供基础。 （摘要完）

DESCRIPTION (provided by applicant): We propose to develop and implement a Knowledge Base and Coordination Center for the Consortium of Cross Organ Mechanism-Associated Phenotypes for Genetic Analyses of Heart, Lung, Blood, and Sleep Diseases (MAPGen). Our team possesses strong expertise in bioinformatics, statistics, computer science, as well as clinical and biological expertise in heart, lung, and blood diseases. We propose three major functions of the center: (1) Develop a knowledge base on interconnections among diseases. We will systematically identify, integrate, and analyze the vast amount of public data (e.g. NCBI GEO, SRA, dbGap, and published papers) to comprehensively describe the shared molecular mechanisms among diseases. We will establish a multi-dimensional disease connectivity map that can be interactively accessed via web- interface. Using this knowledge base, we will design computational approaches to identify biomarkers that can be used to predict more than one disease, to regroup diseases based on the underlying molecular mechanisms, to design novel approaches to predict disease progression, and to identify novel drug usages. (2) Develop a bioinformatics infrastructure for the MAPGen consortium. We will be responsible for the quality control of the data generated by Consortium; we will perform integrative analysis of data generated by different RCs as well those from public domains, in order to gain deep insights and fundamental understandings of the shared molecular mechanisms among the HLBS diseases. We will use the knowledge base developed in Aim 1 to further establish the connections between the HLBS and other diseases. We will work closely with the medical co-investigators at USC as well as all RC teams to develop and validate biological hypotheses. (3) We will establish an Administrative Center to coordinate activities across RCs, including coordination of manuscript and other document preparation; coordination of the activities of all Committees; overall study coordination and quality control; and administering the distribution of additional funds in years 3 and 4. We aim to synergize the effort across all RCs to achieve the goal of understanding the genetic mechanisms responsible for the interconnections among cross-organ diseases. RELEVANCE (See instructions): The proposed projects will facilitate the identification and characterization of common pathobiologic traits and mechanisms cross organ systems, and provide a basis for the rational, mechanism-based development of new diagnostic, prognostic and therapeutic strategies for heart, lung, blood and sleep disorders. (End of Abstract)