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

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）将提供全面的技术检测支持服务 以及对包含此的两个项目中提出的假设驱动研究的分析支持 U19提案的核心从其技术和移植的交叉中获得了最大的整体优势。 特定的专业知识、多维生物审讯的最先进方法以及明确的熟练程度 在柯克博士的领导下，该核心继续利用高级计算分析的长期资产。 该程序的先前迭代以实现移植程序的全面表征，其中 基于多色流式细胞术的免疫分析测试平台的特殊专业知识是。 根据高度标准化和验证，在良好的临床实验室合规环境中进行 标准操作程序，由支持 NHP 移植工作超过 25 年的团队制定。 对于这个已建立的团队来说，已经与国际领先的北卡罗来纳州立大学建立了新的合作关系 在兽医医学领域，整合一个新的平台，用于综合、恒河猴特异性、单细胞 这是第一个全面提供整个RNA序列分析的实验室。 恒河猴中的 TCR 和 BCR 谱库，因此为分析增加了前所未有的粒度 鉴于从这两个项目中获取的数据呈指数增长， 通过招募 Peng 博士，增加了高密度数据分析方面的新专业知识。 这些人在基于序列和基于流的数据集的集成方面拥有丰富的专业知识。 传统的临床结果指标，特别是在非人类灵长类动物研究中，CIC 的关键服务。 将为项目 1 和 2 提供包括：1) 最先进的标本采集、处理和生物样本库；2) 分析型多色流式细胞仪表型分析和细胞内细胞因子染色；3) 单细胞RNA 测序；4) 定量病毒学检测；5) 全面的组织学和免疫组织化学支持； 6) 对测定中出现的数据进行计算分析。 对拟议的灵长类动物研究进行交钥匙评估所需的先进设备，包括特殊的设备 流程和测序平台，以及为整个杜克大学服务的样本处理和生物样本库服务 柯克博士监督下的社区建立了病毒检测设施，对其中三个最重要的地区进行监测。 移植中临床相关病毒：恒河猴巨细胞病毒 (rhCMV)、恒河猴淋巴密码病毒 (rhLCV)（EBV 的恒河猴同源性）和猿猴病毒 40 (SV40)。CIC 还提供常规组织学和检测。 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。 人类和 NHP 的专业知识代表了该 IPC 联盟的特殊优势，进一步促进了高度 拟议研究的转化方面。