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

个性化医疗中心：炎症和免疫生物学系统

• 批准号: 8635895
• 负责人: SEEMA Singh AHUJA
• 金额: --
• 依托单位: SOUTH TEXAS VETERANS HEALTH CARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8635895
• 关键词: Accounting; Achievement; Address; Adoption; Age; Anti-Retroviral Agents; Area; Bioinformatics; Biological; Biological Models; Biometry; Boxing; CD4 Lymphocyte Count; CD4 Positive T Lymphocytes; CD4/CD8 ratio procedure; CD8B1 gene; Caring; Cell Count; Cellular Immunity; Chronic Disease; Clinic; Clinical; Clinical Medicine; Collaborations; Communities; Complex; Contract Services; DNA Methylation; Data; Data Set; Department of Defense; Development; Disease; Elderly; Epidemiology; Epigenetic Process; Funding; Genes; Genetic; Genetic Determinism; Genome; Genomics; Goals; HIV; HIV Infections; HIV-1; Health; Housing; Human; Human Resources; Hypersensitivity skin testing; Immune; Immunity; Immunologics; Immunology; Immunology procedure; In Vitro; Individual; Infection; Inflammation; Interferons; Laboratories; Letters; Maps; Massive Parallel Sequencing; Measures; Medicine; Methodology; Microarray Analysis; Military Personnel; Molecular Biology; Morbidity - disease rate; Natural History; Nature; Patients; Persons; Phenotype; Population Study; Program Research Project Grants; Publishing; RNA; Recovery; Research; Research Design; Research Personnel; Residual state; Resistance; Resources; Risk; SIV; Services; Specimen; Staging; Stratification; System; Systems Biology; T-Cell Activation; T-Lymphocyte; Techniques; Technology; Testing; Thinking; Time; Translational Research; Universities; Veterans; Viral Load result; Work; antiretroviral therapy; base; cohort; cost; disease phenotype; epigenomics; experience; flexibility; genetic variant; genome wide association study; high risk; high throughput technology; immune function; improved; in vivo; indexing; innovation; member; mortality; next generation sequencing; nonhuman primate; novel; programs; reconstitution; response; skills; statistics; tool; transcriptome sequencing; transcriptomics

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.

三个假设驱动的项目（P1、P2、P3）的总体主题是炎症/免疫/艾滋病毒 并且专注、以转化为导向，并致力于促进广泛的串扰/协同作用 调查人员。这些拟议的研究高度以 VA 为中心，将在最近成立的 STVHCS 设有“个性化医疗中心 (CPM)”，并最大限度地利用 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 的资金进一步利用和扩大，这一扩大的设施是 指定为本 PP 的核心。该设施于 2009 年底首次启用，功能齐全，并已 得到多种资金支持（当地VA支持服务费用，PPG的PI已 花费了他可用的灵活的非 NIH 资源来支持该设施）。我们预计将达到高水平 STVHCS 的科学和人力能力建设具有全国影响力，因为我们扩展的核心将 支持最近设立的百万退伍军人项目的遗传/表观遗传/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，所有遗传、表观遗传和 转录组数据来源于；该设施完全配备了现代 Illumina 平台（最近 收购了 HiSeq2000 平台），可以涵盖 当代系统生物学方法。在我们的核心多样化技术中，例如全基因组关联 研究 (GWAS)、通过微阵列和 RNA-seq 进行的转录组学分析以及 DNA 甲基化作图 通过珠芯片可以很容易地进行。鉴于支持大规模生产所需的高水平专业知识 基因组学和转化研究，核心将利用 CPM 的四个现有单位，提供 不同的职能： (i) 基因组学/生物信息学（由当地 VA 支持）； (ii) 生物统计学和 (iii) 临床和 (iv) 行政（由大学附属机构提供资金支持）。核心将由一名协调员 主任（何），在分子生物学和基因组研究方面拥有丰富的经验；这个人也 拥有处理大型数据集的丰富经验，以及强大的“人际交往能力”，可以协同地将 PP的不同成分。 VA 调查人员花费了大量精力来扩大 初步数据反映的生物信息学/生物统计能力。有很强的VA和 UTHSCSA 对 PPG 的支持 [VA 支持核心生物信息学单元和服务合同；和 UTHSCSA 提供行政支持]。 PP 加强了 DoD-VA 的协作研究，因为它利用了 对感染艾滋病毒的一群独特的美国军人进行研究。这提供了一个高水平的平台 协同作用程度，因为每个计划都利用了这个特征明确的约 5000 人队列 前瞻性地收集生物样本，以解决与免疫耗竭相关的尖锐假设 未经治疗和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转录组学的转变奠定了基础 功能和预测医学。因此，PP 的具体目标直接涉及定义 预测抗逆转录病毒治疗（ART）免疫恢复的遗传/转录组特征，提供了新的 治疗的目标。我们建议的工作将显着增强遗传/基因组/表观基因组的能力 我们当地 VA 的研究，可以用作更大的 VA 研究社区的资源。我们相信 通过核心提出的工作将具有变革性，并为 VA 调查人员提供一个平台 开展前沿的当代研究，以推进个性化医疗。因此，VA 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 生物信息技能和专业知识使我们的退伍军人患者受益匪浅。