Biospecimen and Data Core

生物样本和数据核心

• 批准号: 10729469
• 负责人: JOSEPH B SHRAGER
• 金额: $ 32.59万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-19 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10729469
• 关键词: Archives; Biological Assay; Biological Specimen Banks; Cancer Etiology; Cell Communication; Cells; Cessation of life; Clinical; Communities; Data; Data Set; Data Sources; Databases; Deposition; Development; Distant Metastasis; Ensure; Exhibits; Extracellular Matrix; Fibroblasts; Formalin; Freezing; Fresh Tissue; Gene Expression; Gene Expression Profile; Genomics; Goals; Head and Neck Cancer; Health Insurance Portability and Accountability Act; Human; Image; Immune; Immune Tolerance; Immunity; Individual; Ink; Link; Location; Malignant - descriptor; Malignant Neoplasms; Malignant neoplasm of lung; Meta-Analysis; Metastatic Neoplasm to Lymph Nodes; Methods; Mus; Neoplasm Metastasis; Non-Small-Cell Lung Carcinoma; Output; Paraffin Embedding; Patients; Pattern; Phenotype; Positive Lymph Node; Primary Neoplasm; Procedures; Process; Proteomics; Quality Control; Recurrence; Reporting; Reproducibility; Research Personnel; Research Project Grants; Sampling; Specimen; Stains; Standardization; Systems Biology; Tissue Microarray; Tissues; Tumor Biology; Validation; Work; analysis pipeline; biological specimen archives; cancer type; cell type; cohort; computerized data processing; computerized tools; data repository; follow-up; head and neck cancer patient; human tissue; insight; lymph nodes; machine learning algorithm; mouse model; neoplastic cell; novel therapeutic intervention; prognostic significance; reconstruction; repository; single-cell RNA sequencing; transcriptomics; tumor; tumor microenvironment

ABSTRACT/SUMMARY: BIOSPECIMEN AND DATA CORE Our CCSB will dissect how interactions between malignant, stromal and immune cells in the primary tumor and lymph nodes (LN) influence systemic immunity and facilitate distant metastasis, across multiple cancer types. Accordingly, the goal of our Biospecimen and Data Core is to provide expertise and facilities for fresh and archived specimen acquisition, genomic and image data processing, and sharing. This will ensure the provision of high-quality, richly annotated datasets that serve the needs of our Research Projects in mouse and human; to make them widely available to the CSBC and broader community; and to integrate them with external data sources. We will perform the following aims to fulfill our Center goals: (1) We will develop a fresh tissue biospecimen repository of human head and neck cancer (HNSCC) and lung cancer, as well as mouse models of metastasis for single cell RNA sequencing (scRNA-seq) and CODEX analysis. Human specimens including matched primary tumor, LN and distant metastases (when available) from multiple tumor regions will be assigned unique identifiers connecting them to human clinical annotations to develop and populate a HIPAA-compliant REDcap database, while mouse specimens will be linked to detailed experimental information for cross-species phenotypic validation and mechanism study. (2) We will construct TMAs of fixed primary, LN and distant metastases with detailed clinical annotations in order to validate findings from our Research Projects on large independent cohorts. Our TMAs will be constructed from treatment-naïve archived FFPE specimens for head and neck cancer and lung cancer. The TMAs will consist of cores from primary tumors and uninvolved LNs from LN-negative (N0) patients; primary tumors, involved and uninvolved LNs from LN-positive (N+) patients; and distant metastases for a subset of LN-positive patients. Individuals’ tissues will be sampled at multiple locations. The clinical follow-up (survival, occurrence of metastasis) will enable us to infer prognostic significance of our work. (3) we will perform QC, processing, and basic analyses using existing robust pre-processing and analysis pipelines for scRNA-seq, CODEX and IHC data. (4) we will leverage Center-generated data in the context of larger publicly available cohorts. We will identify, curate, pre-process, and analyze public data relevant to the Center’s aims, performing baseline meta-analysis of the relationship between gene expression data and LN/distant metastasis which we can link to insights from our internally generated datasets. We will coordinate with the broader CSBC to make data and analyses available, contribute to standardizing reporting of assay data, and make computational tools widely available. Taken together, the centralization of the acquisition of single-cell proteomic expression (CODEX), scRNA-seq, and spatial transcriptomic data for the two research projects in this proposed BDC will allow studies that employ human and mouse specimens and mouse models to be carried out in a reproducible, efficient, and consistent manner.

摘要/摘要：生物循环和数据核心 我们的CCSB将剖析原发性肿瘤中恶性，基质和免疫球之间的相互作用以及 淋巴结（LN）影响了多种癌症类型的全身免疫力并促进远处转移。 彼此之间，我们的生物测量和数据核心的目标是为新鲜和新鲜的设施提供专业知识和设施 存档的样品获取，基因组和图像数据处理以及共享。这将确保条款 高质量，丰富的注释数据集，这些数据集满足了我们在老鼠和人类中的研究项目的需求； 使其广泛地为CSBC和更广泛的社区提供；并将它们与外部数据集成 来源。我们将执行以下目标以实现我们的中心目标：（1）我们将开发一个新鲜的组织 人头和颈部癌（HNSCC）和肺癌的生物循环库以及小鼠模型 单细胞RNA测序（SCRNA-SEQ）和法典分析的转移。人类标本，包括 将分配匹配的原发性肿瘤，LN和远处转移（如果可用）多个肿瘤区域 将它们连接到人类临床注释的唯一标识符，以开发和填充符合HIPAA REDCAP数据库，而鼠标标本将链接到跨物种的详细实验信息 表型验证和机理研究。 （2）我们将构建固定主要，LN和辨别的TMA 带有详细临床注释的转移，以验证我们的研究项目的发现 独立人群。我们的TMA将由未经治疗的ffpe标本来构建 和颈部癌和肺癌。 TMA将由来自原发性肿瘤的核心和未参考的LN组成 LN阴性（N0）患者；原发性肿瘤，来自LN阳性（N+）患者的涉及和未涉及的LN；和 LN阳性患者子集的远处转移。个人的组织将在多个位置进行采样。 临床随访（生存，发生转移）将使我们能够推断出我们的预后意义 工作。 （3）我们将使用现有强大的预处理和分析执行QC，处理和基本分析 SCRNA-SEQ，CODEX和IHC数据的管道。 （4）我们将利用中心生成的数据 较大的公开队列。我们将确定，策划，预处理和分析与该数据相关的公共数据 中心的目标是，对基因表达数据与 LN/远处转移，我们可以从内部生成的数据集中链接到见解。我们将协调 使用更广泛的CSBC来制作数据和分析，有助于标准化测定数据的报告， 并使计算工具广泛可用。综上 这两个研究项目的蛋白质组学表达（法典），SCRNA-SEQ和空间转录组数据 拟议的BDC将允许进行人类和小鼠标本以及小鼠模型的研究 以可再现，高效和一致的方式。