Human Phenotyping Core

人类表型核心

• 批准号: 10704390
• 负责人: Joel Marvin Guthridge
• 金额: $ 34.1万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-07 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10704390
• 关键词: Address; Area; Autoimmune Diseases; Awareness; B-cell receptor repertoire sequencing; Biological Markers; Blood; Blood Cells; Cells; Cellular Indexing of Transcriptomes and Epitopes by Sequencing; Chromium; Clinical; Competence; Complex; Consultations; Cytometry; Data; Data Analytics; Data Set; Development; Diagnostic; Dimensions; Disease; Dissociation; Education; Emerging Technologies; Epigenetic Process; Equipment; Experimental Designs; Freezing; Funding; Future; Generations; Genetic; Genetic Polymorphism; Genomic DNA; Genomics; Genotype; Heterogeneity; Histology; Human; Human Herpesvirus 4; Human Resources; Image; Immunofluorescence Immunologic; Immunologics; Immunophenotyping; Individual; Institution; Mediator; Methods; Modeling; Molecular; Molecular Disease; Molecular Profiling; Multiomic Data; Oklahoma; Pathogenesis; Pathogenicity; Pathology; Pathway interactions; Patient Care; Patients; Phenotype; Plasma; Population; Process; Proteomics; Quality Control; RNA; Research; Research Personnel; Resolution; Resources; Rheumatism; Sampling; Secure; Serum; Services; T-cell receptor repertoire; Technology; Therapeutic; Time; Tissue Banks; Tissues; Training; Transcript; Transformed Cell Line; Translating; Update; antibody detection; base; biobank; cell fixing; clinical center; experience; human disease; molecular phenotype; multiple omics; nano-string; new technology; patient stratification; phenotypic data; precision medicine; prognostic tool; programs; protein biomarkers; single nucleus RNA-sequencing; single-cell RNA sequencing; success; tissue fixing; transcriptome; transcriptomics; treatment response; whole slide imaging

Human Phenotyping Core Project Summary This highly successful Human Phenotyping Core focuses on providing Center investigators with access to state-of-the-art technologies and methods for utilizing multi-parameter, high-content approaches to assess molecular phenotypes for rheumatic disease research. This Core coordinates expertise and core competencies in transcriptomics, proteomics, high-content cellular immunophenotypes, single-cell multiomics and tissue- based spatial multiomics. As such, it continues as a resource where ORDRCC Investigators can generate, share and analyze the multi-dimensional molecular phenotype data necessary for developing competitive research programs. Beyond giving ORDRCC investigators access to advanced technologies that are currently established at OMRF, this Core offers newly developed services providing access to data analytics in single- cell multi-omics from blood or dissociated tissue, as well as spatially aware tissue-based single-cell approaches. Our platforms enable investigators to define patient molecular profiles based on genetic, transcriptome, cellular, and/or proteomic differences in specific cell populations, as well as at the individual cell level with single cell 10X Genomics multiomic approaches, either 3’ or 5’ scRNA-seq/high-plex CITE-seq + BCR/TCR repertoire, or snRNA-seq/snATAC-seq for epigenetic analyses. Currently evolving approaches using fixed cells or fixed tissue dissociated to single cells on the Chromium X platform offer additional options for difficult to obtain cell populations from existing archival pathology samples in some cases. Spatial technologies have also advanced significantly and include multiomic (transcript and protein biomarkers) approaches. Capitalizing on the magnitude of information available through our carefully processed, well-organized, clinically characterized samples; our ability to provide comprehensive multi-analyte molecular phenotype profiles provide a foundational resource for identifying new research directions and generating new ideas for future collaborative projects. Aims of the updated Human Phenotyping Core are: AIM 1: Assist ORDRCC Investigators, JCIs and Scholars to navigate the stages of project development, experimental design, resource planning and execution of translational and mechanistic studies through Core Management and individual consultations, AIM 2: Provide access and training in use of molecular single-cell and spatial multiomic technologies using the technical personnel experienced in these advanced approaches, AIM 3: Establish data analytics pipelines for quality control, dataset generation and advanced modeling of single-cell and spatial multiomic data, and molecular phenotyping for patient stratification, AIM 4: Evaluate, assess and implement emerging technology and analytics approaches to more accurately assess patient heterogeneity in disease presentation and treatment responses. The HPC evaluates new technologies, working with the institution to secure new equipment or helping investigators understand the strengths and weaknesses of new technologies. The HPC also provides education for JCIs, Scholars, center investigators and lab personnel in these areas.

人类表型核心项目摘要 这个非常成功的人类表型核心致力于为中心研究人员提供 利用多参数、高内涵方法进行评估的最先进技术和方法 风湿病研究的分子表型。该核心协调专业知识和核心能力 在转录组学、蛋白质组学、高内涵细胞免疫表型、单细胞多组学和组织方面 基于空间多组学。因此，它继续作为 ORDRCC 调查员可以生成的资源， 共享和分析发展竞争力所需的多维分子表型数据 研究计划。除了让 ORDRCC 调查人员获得目前的先进技术之外 该核心在 OMRF 建立，提供新开发的服务，可在单一模式下访问数据分析。 来自血液或分离组织的细胞多组学，以及基于空间感知的组织单细胞 接近。我们的平台使研究人员能够根据遗传、 特定细胞群以及单个细胞的转录组、细胞和/或蛋白质组差异 单细胞 10X Genomics 多组学方法（3' 或 5' scRNA-seq/high-plex CITE-seq +）水平 BCR/TCR 库，或用于表观遗传分析的 snRNA-seq/snATAC-seq。目前不断发展的方法使用 Chromium X 平台上的固定细胞或分离为单细胞的固定组织提供了额外的选择 在某些情况下，很难从现有的病理档案样本中获得细胞群。空间技术 也取得了显着进展，包括多组学（转录本和蛋白质生物标志物）方法。 利用我们精心处理、组织良好、 临床特征样本；我们提供全面的多分析物分子表型的能力 概况为确定新的研究方向和产生新的想法提供了基础资源 未来的合作项目。更新后的人类表型核心的目标是： AIM 1：协助 ORDRCC 研究人员、JCI 和学者引导项目开发、实验设计、资源的各个阶段 通过核心管理和个人规划和执行转化和机制研究 咨询，目标 2：提供分子单细胞和空间多组学使用的访问和培训 使用在这些先进方法方面经验丰富的技术人员来技术，目标 3：建立数据 用于质量控制、数据集生成以及单细胞和空间高级建模的分析管道 多组学数据和用于患者分层的分子表型分析，AIM 4：评估、评价和实施 新兴技术和分析方法可更准确地评估患者疾病异质性 表现和治疗反应。 HPC 评估新技术，并与该机构合作 确保新设备的安全或帮助调查人员了解新技术的优点和缺点。 HPC 还为 JCI、学者、中心研究人员和实验室人员提供这些领域的教育。