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

三个假设驱动的项目（P1、P2、P3）的首要主题是炎症/免疫/HIV 并且是集中的，以预防为导向的，并适合于促进广泛的串扰/协同作用， investigators.这些拟议的研究高度以VA为中心，将在最近成立的 “个性化医疗中心（CPM）”设在STVHCS，并充分利用 VA系统中两个基因组设施之一的高通量能力。这些能力将是 通过拟议的PP提供资金，进一步利用和扩大这一扩大的设施， 作为本PP的核心。该设施于2009年底启动，现已全面运作， 得到各种基金的支持（当地VA支持服务费用，PPG的PI 他使用了灵活的非NIH资源来支持这一设施）。我们预计， 在STVHCS进行具有全国影响力的科学和人力能力建设，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/基因组学研究。所以我们 核心作为整个PPG的中心节点或焦点，所有遗传、表观遗传和 转录组数据来自;该设施完全配备了当代Illumina平台（最近 收购的HiSeq 2000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的技术，如全基因组关联 研究（GWAS），通过微阵列和RNA-seq进行转录组学分析，以及DNA甲基化作图 可以容易地执行通过珠芯片。鉴于支持大规模的 基因组学和转化研究，核心将利用CPM的四个现有单位， 独特的职能：（i）基因组学/生物信息学（由当地VA支持）;（ii）生物统计学;（iii）临床和 (iv)行政（由大学附属机构的资金支助）。核心将由一个 主任（He），他在分子生物学和基因组研究方面具有丰富的经验;此人还 在处理大型数据集方面拥有丰富的经验，并具有强大的“人际交往能力”， PP的不同成分。退伍军人事务部的调查人员花费了大量精力 所提交的初步数据所反映的生物信息学/生物统计能力。有强大的VA和 UTHSCSA对PPG的支持[VA支持核心和服务合同的生物信息学单元;以及 UTHSCSA提供行政支持]。PP加强了DoD-VA的合作研究，因为它利用了 对一群感染艾滋病病毒的美国军人进行了研究这提供了一个平台， 协同作用的程度，因为每个计划都利用了这个具有良好特征的约5000人队列， 前瞻性收集生物标本，以解决与免疫耗竭相关的尖锐假设， 在未经治疗和经治疗的艾滋病毒感染情况下的康复。此外，PP将利用现有的 整合基因组学和转录组学数据的合作为从基因到 功能和预测医学。因此，人民党的具体目标直接关系到界定 预测抗逆转录病毒疗法（ART）的免疫恢复的遗传/转录组学特征， 治疗的目标我们提出的工作将大大提高遗传/基因组/表观基因组的能力， 研究在我们当地的VA，并可以作为一个资源，为更大的VA研究社区。我们认为 通过核心计划提出的工作将是变革性的，并为退伍军人事务部调查人员提供一个平台， 进行尖端的当代研究，以推进个性化医疗。因此， 研究社区和MVP项目可以利用我们的基因组，表观基因组，转录组和 生物信息学技能和专业知识，使我们的退伍军人患者受益匪浅。

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.