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/总结：生物标本和数据核心 我们的CCSB将剖析原发性肿瘤中恶性细胞、基质细胞和免疫细胞之间的相互作用， 淋巴结（LN）影响全身免疫并促进多种癌症类型的远处转移。 因此，我们的生物标本和数据中心的目标是提供专业知识和设施， 存档标本采集、基因组和图像数据处理以及共享。这将确保提供 高质量，丰富的注释数据集，满足我们在小鼠和人类研究项目的需求; 使其广泛提供给CSBC和更广泛的社区;并将其与外部数据相结合 源为了实现中心的目标，我们将执行以下目标：（1）我们将开发一种新的组织， 人类头颈癌（HNSCC）和肺癌以及小鼠模型的生物标本库 用于单细胞RNA测序（scRNA-seq）和CODEX分析。人体标本包括 将从多个肿瘤区域分配匹配的原发性肿瘤、LN和远处转移（如可用） 将它们与人类临床注释连接起来的唯一标识符， REDcap数据库，同时将小鼠标本与详细的跨物种实验信息联系起来 表型验证和机制研究。(2)我们将构建固定原发灶、LN和远端的TMA 转移与详细的临床注释，以验证我们的研究项目的结果， 独立的群体。我们的TMA将由头部未经治疗的存档FFPE标本构建 以及颈癌和肺癌。TMA将由来自原发性肿瘤的核心和来自原发性肿瘤的未受累LN组成。 LN阴性（N 0）患者;原发性肿瘤，来自LN阳性（N+）患者的受累和未受累LN;以及 LN阳性患者的一个子集的远处转移。个人的组织将在多个地点取样。 临床随访（生存、转移的发生）将使我们能够推断我们的预后意义 工作(3)我们将使用现有的强大的预处理和分析来执行质量控制、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， 更大的公开可用的队列。我们将识别，策划，预处理和分析与以下内容相关的公共数据： 该中心的目标是对基因表达数据与基因表达之间的关系进行基线荟萃分析， LN/远处转移，我们可以将其与我们内部生成的数据集的见解联系起来。统筹推进 与更广泛的CSBC合作，提供数据和分析，有助于标准化检测数据报告， 并使计算工具广泛使用。综上所述，单细胞的采集集中化 蛋白质组学表达（CODEX），scRNA-seq和空间转录组学数据的两个研究项目，在这个 拟议的BDC将允许使用人类和小鼠标本以及小鼠模型进行研究 以可再现的、有效的和一致的方式。