Core 2: Analytical Core

核心 2：分析核心

• 批准号: 10729279
• 负责人: Nathalie YR Agar
• 金额: $ 35.17万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10729279
• 关键词: Affect; Agar; Animal Model; Biological; Biology; Brain Neoplasms; Cell Communication; Cell Culture Techniques; Cell Nucleus; Cells; Clinical; Clinical Research; Complex; Core Biopsy; Cryoultramicrotomy; Data; Dimensions; Ensure; Equipment; Experimental Models; Expression Profiling; Gene Expression; Gene Expression Profiling; Geography; Glioblastoma; Glioma; Goals; Human; Human Resources; Image; Immune; Immunologics; In Vitro; Knowledge; MHC Class I Genes; Malignant - descriptor; Maps; Measurement; Mediating; Metabolic; Metabolic Pathway; Metabolism; Metadata; Methodology; Methods; Modeling; Molecular; Molecular Profiling; Multiomic Data; Neuroglia; Neurons; Patients; Peptides; Performance; Pharmaceutical Preparations; Phosphorylation; Population; Pre-Clinical Model; Proteomics; Protocols documentation; Quality Control; Reagent; Reproducibility; Resolution; Resources; Sampling; Services; Signal Transduction; Specimen; Study models; System; Systems Biology; Technology; Therapeutic; Thick; Time; Tissues; accurate diagnosis; brain tissue; cell type; clinically relevant; data management; data sharing; drug distribution; dynamical evolution; forest; human tissue; image guided; imaging biomarker; information gathering; mass spectrometric imaging; mathematical model; metabolomics; neoplastic cell; phosphoproteomics; pre-clinical; programs; protein expression; single nucleus RNA-sequencing; spatial integration; tissue culture; tool; transcriptome sequencing; transcriptomics; treatment response; tumor; tumor microenvironment

ABSTRACT – ANALYTICAL CORE The Analytical Core will serve as a central resource for the deep systems-level molecular characterization of biological samples generated by the Projects and from the Biospecimens Core. The primary objective of this Core is to integrate diverse single cell, bulk, and spatial analytical platforms to define the complex interactions between brain tumor cells and the associated brain tumor microenvironment (TME). To this end, we have developed an analytical platform encompassing transcriptional profiling at the single cell, single nuclei, and bulk tissue scale; protein expression profiling, phosphoproteomics and immunopeptidomics with cell type-specific resolution; and quantitative metabolomics and drug distribution profiling with high spatial resolution by mass spectrometry imaging (MSI). These complementary analytical approaches have the requisite sensitivity to generate ultra-deep systems-level molecular profiling of 10-20 micron thick tissues from single core biopsies; performance of our platform has already been demonstrated on multiple image-guided core biopsies from geographically distinct regions of a GBM tumor. Multi-omics data acquired in our Analytical Core will be managed using a FAIR compliant metadata management tool that prioritizes connections between samples and defines discrete sample types that can be freely connected as described in the Overall Section of our proposal. The Analytical Core will provide expert personnel, facilitate the sharing of knowledge within the program, and maintain the sophisticated equipment necessary to generate data for both Projects. By acting as a common resource, the Analytical Core provides expertise for each Project.

摘要 – 分析核心 分析核心将作为深度系统级分子表征的中心资源 项目和生物样本核心生成的生物样本。此举的首要目标 核心是整合不同的单细胞、体块和空间分析平台来定义复杂的相互作用 脑肿瘤细胞和相关脑肿瘤微环境（TME）之间的关系。为此，我们有 开发了一个分析平台，涵盖单细胞、单核和批量的转录分析 组织规模；具有细胞类型特异性的蛋白质表达谱、磷酸化蛋白质组学和免疫肽组学 解决;以及具有高质量空间分辨率的定量代谢组学和药物分布分析 光谱成像（MSI）。这些互补的分析方法具有必要的敏感性 从单核心活检中生成 10-20 微米厚组织的超深系统级分子分析； 我们平台的性能已在多个图像引导核心活检中得到证明 GBM 肿瘤的地理上不同的区域。我们的分析核心中获取的多组学数据将得到管理 使用符合 FAIR 标准的元数据管理工具，对样本之间的连接进行优先级排序并定义 可以按照我们提案的总体部分中所述自由连接的离散样本类型。这 分析核心将提供专家人员，促进项目内的知识共享，并维护 为这两个项目生成数据所需的先进设备。通过充当公共资源， 分析核心为每个项目提供专业知识。