Center for Personalized Medicine: Systems of Biology of Inflammation and Immunity

这三个假设驱动的项目(P1、P2、P3)的主要主题是炎症/免疫/艾滋病毒 并专注于翻译，旨在促进广泛的串扰/协同 调查人员。这些拟议的研究高度以退伍军人管理局为中心，将在最近建立的 “个性化医疗中心(CPM)”设在STVHCS，并最大限度地利用 VA系统中只有两个基因组设施中的一个的高通量能力。这些能力将是 通过提议的PP提供的资金进一步利用和扩展，扩展后的设施是 被指定为本PP的核心。该设施最初于2009年底启动，现已全面运作，并已 得到了各种资金的支持(当地VA支持服务成本，PPG的PI有 花费可供他使用的灵活的非NIH资源来支持这一设施)。我们预计会有很高水平的 STVHCS的科学和人力能力建设对全国产生影响，因为我们扩大的核心将 支持最近建立的百万退伍军人项目的遗传/表观遗传学/基因组学研究。因此，我们的 核心作为整个PPG的中心节点或焦点运行，所有的遗传、表观遗传和 转录数据来自；该设施完全配备了当代Illumina平台(最近 收购的HiSeq2000平台)，可以涵盖 当代系统的生物学方法。在我们的核心多样化技术中，如全基因组关联 研究(GWAS)、通过微阵列和RNA-SEQ进行的转录组学分析以及DNA甲基化图谱 通过BeadChip可以很容易地执行。考虑到支持大规模 基因组学和翻译研究，核心将利用CPM现有的四个单位，这些单位提供 明确的职能：(1)基因组学/生物信息学(由当地退伍军人管理局支助)；(2)生物统计学；(3)临床和 (Iv)行政管理(由大学附属机构提供资金支持)。核心将由一个人协调 董事(何)，在分子生物学和基因组研究方面有丰富经验；该人还 在处理大型数据集方面拥有丰富的经验，以及强大的“人际交往技能”，能够协同地将 PP的不同成分。退伍军人管理局的调查人员花费了大量的精力来扩大 所提供的初步数据所反映的生物信息学/生物统计能力。有很强的VA和 UTHSCSA对PPG的支持[退伍军人事务部支持核心和服务合同的生物信息股；以及 UTHSCSA提供行政支持]。PP加强了国防部-退伍军人事务部的协作研究，因为它利用 一个独特的感染艾滋病毒的美国服务人员队列。这提供了一个平台 每个计划利用这一具有良好特征的约5000人与BANKED的队列时的协同程度 前瞻性地收集生物标本，以解决与免疫衰竭和 在未经治疗和治疗的艾滋病毒感染的情况下恢复。此外，PP将利用现有的 整合基因组学和转录组数据的合作为从基因到 功能和预测医学。因此，PP的具体目标直接涉及到定义 预测抗逆转录病毒治疗(ART)免疫恢复的遗传/转录特征，提供了新的 治疗的目标。我们提议的工作将极大地建立遗传/基因组/表观基因组学的能力 在我们当地的退伍军人事务部进行研究，并可作为更大的退伍军人事务部研究社区的资源。我们相信 通过核心提出的工作将是变革性的，并为退伍军人管理局调查人员提供一个平台 开展当代前沿研究，推进个性化医疗。因此，退伍军人事务部 研究界和MVP项目可以利用我们的基因组、表观基因组、转录和 生物信息学技能和专业知识，极大地造福于我们的退伍军人患者。

The three hypotheses driven Projects (P1, P2, P3) have the overarching theme of inflammation/immunity/HIV and are focused, translationally-oriented, and geared to promote extensive crosstalk/synergy among investigators. These proposed studies, that are highly VA-centric, will be conducted at the recently established "Center of Personalized Medicine (CPM)" housed at the STVHCS, and leverage to the fullest extent with the high-throughput capabilities of only one of two genomic facilities in the VA system. These capacities will be tapped into and expanded upon further via funding from the proposed PP and this expanded facility is designated as the Core of this PP. This facility, initially launched at the end of 2009, is fully functional and has been supported by a variety of funds (local VA supports the service costs and the PI of the PPG has expended flexible non-NIH resources available to him to support this facility). We anticipate a high level of scientific and manpower capacity building at STVHCS with national impact because our expanded Core will bolster genetic/epigenetic/genomics studies for the recently established Million Veterans Project. Hence, our Core operates as a central node or focal point of the entire PPG from which all genetic, epigenetic and transcriptomic data emanates from; this facility is fully equipped with contemporary Illumina platforms (recently acquired HiSeq2000 platform) that can cover the entire range of methodologies that are encompassed in contemporary system's biology approach. In our Core diverse techniques such as genome wide association studies (GWAS), transcriptomics analysis by microarrays and RNA-seq, and DNA methylation mapping through beadchip can be readily performed. Given the high level of expertise required to support high-scale genomics and translational research, the Core will tap into the four existing units of the CPM that provide distinct functions: (i) Genomics/Bioinformatics (supported by local VA); (ii) Biostatistics and (iii) Clinical and (iv) Administrative (supported by funds from the University affiliate). The Core will be coordinated by one Director (He), who has extensive experience in molecular biology and genomic research; this individual also has vast experience in handling large data sets, and strong "people skills" to synergistically bring together the different components of the PP. The VA investigators have expended significant energies in expanding bioinformatics/biostatistical capacity as reflected by the preliminary data presented. There is strong VA and UTHSCSA support for the PPG [VA supports Bioinformatics Unit of the Core and service contracts; and UTHSCSA provides administrative support]. The PP enhances collaborative DoD-VA research as it capitalizes on a unique cohort of US Service personnel who acquired HIV infection. This provides the platform for a high degree of synergy as each Program capitalizes on this well characterized ~5000-person cohort with banked prospectively collected biological specimens to address incisive hypotheses related to immune depletion and recovery in the context of untreated and treated HIV infection. Furthermore, the PP will tap into existing collaborations to integrate genomics and transcriptomics data setting the stage for moving from genes to function and predictive medicine. Thus, the specific aims of the PP directly relate to defining genetic/transcriptomic signatures that predict immune recovery on antiretroviral therapy (ART), providing novel targets for therapy. The work we propose will significantly build capacity for genetic/genomic/epigenomic research at our local VA and can be used as a resource for the larger VA research community. We believe that the work proposed through the core will be transformative and provide a platform for VA investigators to conduct cutting edge contemporary research towards advancing Personalized Medicine. Thus, the VA research community and the MVP project can leverage our genomic, epigenomic, transcriptomic and bioinformatic skills and expertise to immensely benefit our patients who are veterans.