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.

人类表型核心项目总结 这一非常成功的人类表型分析核心专注于为中心调查人员提供访问 利用多参数、高含量方法评估的最新技术和方法 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、高含量细胞免疫表型、单细胞多重组学和组织- 基于空间多组学。因此，它继续作为ORDRCC调查人员可以生成、 共享和分析发展竞争力所需的多维分子表型数据 研究项目。除了使ORDRCC调查人员能够访问目前 在OMRF成立，这一核心提供新开发的服务，提供访问数据分析的单一- 来自血液或分离组织的细胞多组学，以及空间感知的基于组织的单细胞 接近了。我们的平台使研究人员能够根据基因、 转录组、细胞和/或蛋白质组在特定细胞群体中以及在单个细胞上的差异 与单细胞10X基因组多组学方法水平相同，3‘或5’scRNA-seq/High-plex Cite-seq+ BCR/TCR谱系，或用于表观遗传分析的SnRNA-Seq/SnATAC-seq。目前正在发展的方法使用 Chromium X平台上分离到单个细胞的固定细胞或固定组织提供了额外的选项 在某些情况下，很难从现有的档案病理样本中获得细胞群体。空间技术 也取得了重大进展，包括多组学(转录本和蛋白质生物标记物)方法。 充分利用我们精心处理、组织严密、 具有临床特征的样本；我们提供全面的多分析物分子表型的能力 配置文件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。更新的人类表型核心的目标是：目标1：协助ORDRCC 研究人员、JCI和学者在项目开发、实验设计、资源 通过核心管理和个人来规划和执行翻译和机械研究 会商，目标2：提供使用分子单细胞和空间多组体的途径和培训 使用在这些高级方法方面经验丰富的技术人员的技术，目标3：建立数据 用于单细胞和空间的质量控制、数据集生成和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，目标4：评估、评估和实施 用于更准确地评估疾病患者异质性的新兴技术和分析方法 陈述和治疗反应。HPC评估新技术，与该机构合作 保护新设备或帮助调查人员了解新技术的优势和劣势。 HPC还为这些领域的JCI、学者、中心调查人员和实验室人员提供教育。