Precancer Atlas of Familial Adenomatous Polyposis

家族性腺瘤性息肉病癌前图谱

基本信息

批准号：
10820046
负责人：
JAMES M. FORD
金额：
$ 97.09万
依托单位：
STANFORD UNIVERSITY
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：
2023-04-04 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10820046
关键词：
3-Dimensional Atlases Automobile Driving Benign Biological Assay Biology Cancer Etiology Cells Cessation of life Colectomy Collection Colon Colon Adenocarcinoma Colonoscopy Colorectal Colorectal Cancer Communities Computer software Data Data Analyses Data Collection Data Set Deposition Development Dimensions Disease Disease Progression Endoscopy Event Familial Adenomatous Polyposis Syndrome Familial colorectal cancer Funding Genetic Genomics Heterogeneity Hi-C Hospitals Human Image Imaging technology Immune System Diseases Individual Intestines Lesion Malignant Neoplasms Manuscripts Maps Medical Medical Records Metadata Methylation Modeling Molecular Mucous Membrane Mutation Operative Surgical Procedures Organoids Paper Patients Persons Pilot Projects Polyps Precancerous Polyp Proteins Proteome Proteomics Protocols documentation Publications Publishing RNA Sampling Serum Technology Testing Text Tissue Sample Tissues United States Visit Whole Blood Work biobank colon microbiome cytokine data submission epigenomics experimental study follow-up genome sequencing lipidome lipidomics metabolome metabolomics microbiome molecular imaging multiple omics polyposis predictive modeling premalignant prophylactic recruit single cell sequencing single nucleus RNA-sequencing spatiotemporal transcriptome transcriptomics tumor tumor progression tumor-immune system interactions whole genome

项目摘要

Project Summary We are building a Precancer Atlas of colorectal cancer from Familial Adenomatous Polyposis (FAP) patients. We have built a biobank containing thousands of samples from 78 donors. We have applied genomic, epigenomic, proteomic, lipidomic, metabolomic, transcriptomic, and spatial assays to characterize the molecular changes occurring during the progression from normal mucosa to cancer. We propose to use an integrated approach to further develop our Precancer Atlas. By profiling multiple polyps from the same patient, our Precancer Atlas enables characterization of the early events driving colorectal cancer. We will: 1) Complete procurement of longitudinal tissue samples from 100 donors during surveillance colonoscopy and during prophylactic surgical colectomy, including whole blood, serum, normal colonic tissue, colon microbiome, benign pre-cancerous polyps, dysplastic precancerous polyps and colon adenocarcinomas. The material will be used for our own center and will also be available to the Human Tumor Atlas Network (HTAN). Medical records, longitudinal samples and all relevant metadata will also be collected. 2) Characterize the tissue samples with state-of-the-art omics and imaging technologies. 3) Integrate results from -omics, imaging and medical information, to build a spatiotemporal, multidimensional, integrative multi-omics cancer atlas, and develop longitudinal and predictive models for PreCancer biology and progression. 4) Complete our establishment of multi-omics technologies, finishing our CODEX, snRNA-seq and organoid profiling. 5) Complete the publication of our “multiscale deep data analysis” on a large number of samples from a few people. Use this information to guide additional data collection, including our follow- up snRNA-seq experiments and our hypothesis-testing experiments in organoid models. 6) Identify factors (e.g. germline genetics, immune dysfunction) contributing to polyp heterogeneity and build disease progression models based on these data. 7) Make all biospecimens, information, protocols and software available to the PCA, HTAN and the general scientific community.

项目概要我们正在构建家族性腺瘤性息肉病结直肠癌的癌前图谱我们建立了一个包含来自 78 名捐赠者的数千份样本的生物库。应用了基因组学、表观基因组学、蛋白质组学、脂质组学、代谢组学、转录组学和空间测定来表征从进展过程中发生的分子变化我们建议使用综合方法来进一步开发我们的方法。通过分析同一患者的多个息肉，我们的癌前图谱可以实现驱动结直肠癌的早期事件的特征我们将： 1) 监测期间完整采集 100 名捐献者的纵向组织样本结肠镜检查和预防性结肠切除术期间，包括全血、血清、正常值结肠组织、结肠微生物群、良性癌前息肉、发育不良癌前息肉该材料将用于我们自己的中心，也将用于治疗结肠腺癌。可用于人类肿瘤图谱网络 (HTAN) 医疗记录、纵向样本。所有相关元数据也将被收集。 2) 使用最先进的组学和成像技术表征组织样本。 3）整合组学、影像和医学信息的结果，构建时空、多维、综合多组学癌症图谱，并开发纵向和预测性癌症前期生物学和进展的模型。 4）完成我们多组学技术的建立，完成我们的CODEX、snRNA-seq 和类器官分析。 5）完成我们对大量样本的“多尺度深度数据分析”的发表使用这些信息来指导其他数据收集，包括我们的后续数据 snRNA-seq 实验和我们在类器官模型中的假设检验实验。 6) 确定导致息肉的因素（例如种系遗传学、免疫功能障碍）异质性并根据这些数据建立疾病进展模型。 7) 使所有生物样本、信息、方案和软件可供 PCA、HTAN 和一般科学界。