Core 2: Analytical Core

核心 2：分析核心

基本信息

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
项目类别：
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

项目摘要

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该项目和生物样本核心生成的生物样本是该项目的主要目标。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为此，我们研究了脑肿瘤细胞和相关脑肿瘤微环境（TME）之间的关系。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蛋白质表达谱、磷酸蛋白质组学和细胞类型特异性免疫肽组学分辨率；以及按质量进行高空间分辨率的定量代谢组学和药物分布分析这些互补的分析方法对光谱成像 (MSI) 具有必要的灵敏度。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将管理在我们的分析核心中获取的 GBM 肿瘤的不同地理区域。使用符合公平标准的元数据管理工具，该工具可以优先考虑样本之间的连接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。分析核心将提供专家人员，促进项目内的知识共享，并维护为两个项目生成数据所需的先进设备。分析核心为每个项目提供专业知识。