Integration of Clinical, Genomic and Proteomic Data using a Bioinformatic Approac

描述(由申请人提供)： 分子生物学的重大发展，加上基因组学和蛋白质组学的进步，导致了生物数据的爆炸性增长。为了从这些庞大的数据库中获得有用的相关信息(例如通过数据挖掘)，必须使用先进的计算方法和硬件。迅速发展的生物信息学领域，生物学、计算机科学和信息技术融合为一门学科，有可能成为医学信息学和实验科学之间的桥梁。在这项建议中，我们将重点放在一组独特的HIV-1感染者，长期非进展者(LTNP)，他们可以在没有抗逆转录病毒治疗的情况下保持无症状15年。LTNP状态的背后有许多因素。该项目将我们目前的生物信息学研究向更具翻译性的方向扩展，将开发一个复杂的临床和实验数据库，并将通过强大的信息学工具进行分析，以确定导致LTNP表型的关键基因和蛋白质。我们假设，使用我们专门开发的创新信息学技术，我们将准备一个公开可用的、大型的、互动的数据库，其中包含关于HIV-1感染患者的医疗、基因组和蛋白质组信息，可以通过查询来指导临床和公共卫生层面的理性、基于证据的决策。我们的建议代表了3个专业研究小组之间富有成效的合作伙伴关系，这些小组在以下方面拥有广泛的专业知识：a)艾滋病毒-1疾病的临床管理，b)分子和细胞免疫病毒学，以及c)生物信息学和计算科学。这个生物医学信息学方案的目标是表征和有效利用从基础生物医学研究中获得的数据，并将其与临床结果相结合。提出了以下具体目标。具体目标1：使用最先进的基因组和蛋白质组技术，识别我们特定的HIV-1感染患者队列中独有的功能基因和蛋白质。具体目的2：利用SNP分析和实时定量聚合酶链式反应来评估人类等位基因变异在影响HIV-1疾病进展速度中的作用。具体目标3：开发新的计算工具，以分析和整合来自我们的HIV-1患者队列的基因组、蛋白质组和临床数据，并将它们转换为与HIV-1感染患者的发病机制、传播和治疗反应有关的临床有用信息。这将涉及以下方面的设计：面向数据挖掘的模式；在数据仓库中集成基因组、蛋白质组和临床数据的高级算法；以及探索宿主基因变异和艾滋病毒疾病之间关联的指标和方法。最终，该数据库将作为可公开访问的资源在网络上提供。这项研究将有助于我们从根本上了解HIV感染的发病机制，并确定新的疾病进展生物标志物和潜在的治疗分子靶点。

DESCRIPTION (provided by applicant): Major developments in molecular biology, coupled with strides in genomics and proteomics, have led to an explosive growth in biological data. To obtain usable, relevant information from these vast databases (e.g. through data mining) it is mandatory to use advanced computational methods and hardware. The rapidly expanding field of bioinformatics, where biology, computer science, and information technology merge to form a single discipline, has the potential to serve as a bridge between medical informatics and experimental science. In this proposal we focus on a unique cohort of HIV-1 infected subjects, long term non-progressors (LTNP), who can remain asymptomatic for >15 yr without antiretroviral therapy. Many factors underlie the LTNP state. This project, which expands our current bioinformatics studies in a more translational direction, will develop a complex clinical and experimental database that will be analyzed by powerful informatics tools to identify key genes and proteins that contribute to the LTNP phenotype. We hypothesize that using innovative informatics technology that we specifically develop, we shall prepare a publicly available, large, interactive database containing medical, genomic and proteomic information on HIV-1 infected patients that can be queried to guide rational, evidence-based, decision making at both the clinical and public health levels. Our proposal represents a productive partnership between 3 specialized research groups, with extensive expertise in: a) clinical management of HIV-1 disease, b) molecular and cellular immunovirology, and c) bioinformatics and computational sciences. The goal of this biomedical informatics proposal is the characterization and efficient utilization of data obtained from basic biomedical research and integrate it with clinical outcome. The following specific aims are proposed. Specific Aim 1: To identify functional genes and proteins that are unique to our specific HIV-1 infected patient cohorts using state of the art genomic and proteomic technologies. Specific Aim 2: To evaluate the role of human allelic variants in influencing the rate of HIV-1 disease progression using SNP analysis and real time, quantitative PCR. Specific Aim 3: To develop new computational tools to analyze and integrate genomic, proteomic, and clinical data from our HIV-1 patient cohorts and convert them into clinically useful information relating to the pathogenesis, transmission and therapeutic response of HIV-1 infected patients. This will involve the design of: data mining-oriented schemas; advanced algorithms for integrating genomic, proteomic, and clinical data in a data warehouse; and metrics and methods to explore the association between host genetic variations and HIV disease. Ultimately this database will be provided on the web as a publicly accessible resource. This study will contribute to our fundamental understanding of the pathogenesis of HIV infections and identify new biomarkers of disease progression and potential molecular targets for therapy.