Computational Immunobiology Core

计算免疫生物学核心

• 批准号: 10622057
• 负责人: Allan D. Kirk
• 金额: $ 82.76万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10622057
• 关键词: Adaptive Immune System; Antigens; Archives; Autopsy; B-Lymphocytes; Biological; Biological Assay; Biopsy; Cell Count; Cells; Characteristics; Charge; Clinical; Clonal Deletion; Clone Cells; Collaborations; Color; Communicable Diseases; Communities; Computational Biology; Computer Analysis; Core Facility; Cryopreservation; Cytomegalovirus; Data; Data Analyses; Data Analytics; Data Set; Dimensions; Elements; Environment; Environmental Exposure; Equipment; Flow Cytometry; Funding; Future; Genetic Polymorphism; Genetic Transcription; Growth; Histologic; Histology; Human; Human Herpesvirus 4; Immune; Immune response; Immunoassay; Immunobiology; Immunocompromised Host; Immunohistochemistry; Immunology; Immunology procedure; Individual; Infrastructure; Infusion procedures; Injury; International; Laboratories; Leadership; Lymphocryptovirus; Lymphocyte; Macaca mulatta; Management Information Systems; Maps; Measurement; Methods; Monitor; Organ; Organ Transplantation; Outcome; Peripheral; Peripheral Blood Mononuclear Cell; Phenotype; Plasma; Plasma Cells; Population; Preparation; Primates; Procedures; RNA; RNA Sequence Analysis; Research; Research Personnel; Research Support; Rhesus; Risk; Sampling; Scientist; Serum; Services; Simian virus 40; Specimen; Specimen Handling; Stains; Standardization; Stress; Supervision; Technical Expertise; Testing; Therapeutic; Thymus Gland; Tissue Grafts; Tissue Sample; Tissues; Transplant-Related Disorder; Transplantation; Universities; Veterinary Medicine; Viral; Virus; Work; anergy; biobank; cell type; chemokine; clinically relevant; cytokine; density; exhaustion; experience; experimental study; forging; imprint; in vivo; insight; large datasets; lymph nodes; monocyte; multidimensional data; nonhuman primate; novel; pathogenic virus; pharmacologic; programs; recruit; research study; resilience; response; sequencing platform; single-cell RNA sequencing; testing services; Adaptive Immune System; Antigens; Archives; Autopsy; B-Lymphocytes; Biological; Biological Assay; Biopsy; Cell Count; Cells; Characteristics; Charge; Clinical; Clonal Deletion; Clone Cells; Collaborations; Color; Communicable Diseases; Communities; Computational Biology; Computer Analysis; Core Facility; Cryopreservation; Cytomegalovirus; Data; Data Analyses; Data Analytics; Data Set; Dimensions; Elements; Environment; Environmental Exposure; Equipment; Flow Cytometry; Funding; Future; Genetic Polymorphism; Genetic Transcription; Growth; Histologic; Histology; Human; Human Herpesvirus 4; Immune; Immune response; Immunoassay; Immunobiology; Immunocompromised Host; Immunohistochemistry; Immunology; Immunology procedure; Individual; Infrastructure; Infusion procedures; Injury; International; Laboratories; Leadership; Lymphocryptovirus; Lymphocyte; Macaca mulatta; Management Information Systems; Maps; Measurement; Methods; Monitor; Organ; Organ Transplantation; Outcome; Peripheral; Peripheral Blood Mononuclear Cell; Phenotype; Plasma; Plasma Cells; Population; Preparation; Primates; Procedures; RNA; RNA Sequence Analysis; Research; Research Personnel; Research Support; Rhesus; Risk; Sampling; Scientist; Serum; Services; Simian virus 40; Specimen; Specimen Handling; Stains; Standardization; Stress; Supervision; Technical Expertise; Testing; Therapeutic; Thymus Gland; Tissue Grafts; Tissue Sample; Tissues; Transplant-Related Disorder; Transplantation; Universities; Veterinary Medicine; Viral; Virus; Work; anergy; biobank; cell type; chemokine; clinically relevant; cytokine; density; exhaustion; experience; experimental study; forging; imprint; in vivo; insight; large datasets; lymph nodes; monocyte; multidimensional data; nonhuman primate; novel; pathogenic virus; pharmacologic; programs; recruit; research study; resilience; response; sequencing platform; single-cell RNA sequencing; testing services

ABSTRACT – Computational Immunobiology Core The Computational Immunobiology Core (CIC) will provide comprehensive technical assay support services and analytic support for the hypothesis-driven research studies proposed in the two Projects comprising this U19 proposal. The Core derives its greatest overall strength from its intersection of technical and transplant- specific expertise, state-of-the art methods for multidimensional biological interrogation, and explicit proficiency in advanced computational analytics. Led by Dr. Kirk, the Core continues to utilize the longstanding assets of prior iterations of this program to achieve comprehensive characterization of transplant procedures, with particular expertise in polychromic flow cytometry-based platforms for immune profiling. Assay testing is performed in a Good Clinical Laboratory compliant environment according to highly standardized and validated Standard Operating Procedures, by a team that has been supporting NHP transplant work for over 25 years. To this established team, a new collaboration has been forged with NC State University, an international leader in veterinary medicine, to incorporate a novel platform for comprehensive, rhesus macaque-specific, single cell RNA sequence analysis. This is the first lab to comprehensively provide RNA sequence analysis for the entire TCR and BCR repertoire in the rhesus macaque, and as such, adds unprecedented granularity to the analysis of the in vivo studies proposed in the two Projects. Given the exponential growth in data acquired from these capabilities, new expertise in high-density data analytics has been added through the recruitment of Drs. Peng and Chan. These individuals have extensive expertise in the integration of sequence- and flow-based datasets with traditional metrics of clinical outcome, specifically in nonhuman primate studies. The key services the CIC will provide to Projects 1 and 2 include: 1) state-of-the-art specimen capture, processing, and biobanking; 2) analytical polychromatic flow cytometry phenotyping and intracellular cytokine staining; 3) single cell RNA sequencing; 4) quantitative virologic testing; 5) comprehensive histology and immunohistochemistry support; and 6) computational analysis for the data emerging from the assays. The present core facilities house all the advanced equipment required for turn-key assessment of the proposed primate studies, including exceptional flow and sequencing platforms, and a specimen processing and biobanking service that serves the entire Duke community under Dr. Kirk’s supervision. The established viral testing facility monitors three of the most clinically relevant viruses in transplantation: Rhesus Cytomegalovirus (rhCMV), Rhesus Lymphocryptovirus (rhLCV) (rhesus homology of EBV), and Simian Virus 40 (SV40). The CIC also provides routine histology and immunohistochemistry assays through our immunohistochemistry service laboratory, allowing each project to examine the effects of the experimental manipulations on key donor and host tissues. The juxtaposition of human and NHP expertise represents a particular strength of this IPC consortium, further facilitating the highly translational aspects of the proposed studies.

摘要 - 计算免疫生物学核心 计算免疫生物学核心（CIC）将提供全面的技术评估支持服务 以及对两个项目中提出的假设驱动的研究的分析支持， U19提案。核心从技术和移植的交汇处获得了最大的总体强度 - 特定的专业知识，多维生物学询问的最先进方法以及明确的熟练程度 在高级计算分析中。由柯克博士领导，核心继续利用 此计划的事先迭代以实现移植程序的全面表征 基于多色流式细胞仪的平台，用于免疫分析的特定专业知识。测定测试是 根据高标准化和经过验证的良好临床实验室环境进行 一支支持NHP移植工作已有25年以上的团队的标准操作程序。 对于这个既定的团队，与国际领导者NC州立大学建立了新的合作 在兽医学中，要合并一个新颖的平台，用于全面的恒河猕猴特异性单细胞 RNA序列分析。这是第一个全面提供整个RNA序列分析的实验室 恒河猕猴中的TCR和BCR曲目，因此增加了前所未有的粒度 在这两个项目中提出的体内研究中。鉴于从这些数据中获得的数据呈指数增长 通过招募DRS添加了功能，高密度数据分析方面的新专业知识。彭 和Chan。这些人在序列和基于流的数据集的集成方面具有广泛的专业知识 具有传统的临床结果指标，特别是在非人类灵长类动物研究中。关键服务CIC 将为项目1和2提供提供：1）最先进的标本捕获，加工和生物库； 2） 分析多色流式细胞仪表型和细胞内细胞因子染色； 3）单细胞RNA 测序； 4）定量病毒学测试； 5）全面的组织学和免疫组织化学支持； 6）从测定中出现的数据的计算分析。目前的核心设施所有 拟议的灵长类动物研究所需的高级设备，包括特殊 流程和测序平台，以及为整个公爵提供服务的标本处理和生物库服务 在柯克博士的监督下的社区。已建立的病毒测试设施监测最多的三个 移植中临床相关的病毒：恒河猴（RHCMV），恒河猴淋巴结病毒 （RHLCV）（EBV的恒河类同源性）和Simian病毒40（SV40）。 CIC还提供常规的组织学和 通过我们的免疫组织化学服务实验室进行免疫组织化学测定，使每个项目能够 检查实验操作对关键供体和宿主组织的影响。并置 人类和NHP专业知识代表了该IPC财团的特殊优势，进一步支持了高度支持 拟议研究的翻译方面。