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：生物质谱学和数据核心 我们的CCSB将剖析原发肿瘤中恶性、间质和免疫细胞之间的相互作用 淋巴节(LN)影响全身免疫，促进多种癌症类型的远处转移。 因此，我们的Biosecimen和Data Core的目标是为新鲜和 存档标本采集、基因组和图像数据处理和共享。这将确保提供 高质量、注释丰富的数据集，满足我们的老鼠和人类研究项目的需要； 将它们广泛提供给CSBC和更广泛的社区；并将它们与外部数据相结合 消息来源。我们将完成以下目标以实现我们的中心目标：(1)我们将开发一种新鲜的组织 人头颈部癌(HNSCC)和肺癌以及小鼠模型的生物谱系资料库 单细胞RNA测序(scRNA-seq)和Codex分析。人体标本，包括 匹配的原发肿瘤、LN和来自多个肿瘤区域的远处转移(如果可用)将被分配 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的 RedCap数据库，而小鼠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)构建固定初级、LN和远距离的TMA 转移与详细的临床注释，以验证我们的研究项目的结果在大 独立的队列。我们的TMA将由头部原始存档的FFPE样本构建 以及宫颈癌和肺癌。TMA将由来自原发肿瘤的核心和来自 LN阴性(N0)患者；LN阳性(N+)患者的原发肿瘤、受累和未受累的LN；以及 部分LN阳性患者的远处转移。个人的组织将在多个地点进行采样。 临床随访(存活、转移的发生)将使我们能够推断本组患者的预后意义。 工作。(3)我们将利用现有的稳健的前处理和分析来执行QC、处理和基本分析 ScRNA-seq、CODEX和IHC数据的管道。(4)我们将在以下背景下利用中心生成的数据 更大的公开可用队列。我们将识别、管理、预处理和分析与 中心的目标，对基因表达数据和 LN/远处转移，我们可以链接到我们内部生成的数据集的洞察力。我们会协调 通过更广泛的CSBC提供数据和分析，有助于标准化报告化验数据， 并使计算工具广泛可用。综上所述，集中化的单细胞收购 这两个研究项目的蛋白质组表达(Codex)、scRNA-seq和空间转录数据 拟议的BDC将允许进行使用人类和小鼠标本和小鼠模型的研究 以可重复的、有效的和一致的方式。