Tissue Procurement Center (TPC) Supporting the Somatic Mosaicism across Human Tissues (SMaHT) Network

项目主任/首席调查员(托马斯·贝尔，J.)： 项目总结： 人体组织体细胞嵌合体(SMAHTT)网络项目将建立第一个全面的 所有发育阶段的人体组织中体细胞嵌合体导致的遗传变异的公共资源 人体的各个层次。SMAHT网络将有多个中心，以支持三个中心的发展 主要举措：1)体细胞变异发现，2)数据分析和网络组织，3)技术 和工具开发。来自SMAHT网络项目的数据将提供无与伦比的研究资源 让研究人员对健康人类体细胞嵌合体过程中的遗传变异获得新的见解 纸巾。除了利用新出现的方法学来研究人体组织中的体细胞嵌合体外， SMAT计划包括一项道德、法律、社会影响(ELSI)研究，以加深我们对 用于体细胞嵌合体研究的人体组织捐献中的ELSI因子。 为了支持SMATH网络项目的推进，这项提案将设立一个组织采购 中心(TPC)，该中心将向SMATH网络提供来自 在他们的实验分析中，在所有三个发育层中都有同一个人。迎接挑战 对于SMAT网络，我们的建议是利用多机构的努力，在人体组织方面拥有广泛的专业知识 收集、研究、病理、成像、生物库和ELSI研究分析。这方面的专业知识是必不可少的。 为了TPC成功地提供注释良好的合适的组织样本以支持产生可靠的 以及来自SMAT网络实验程序的可重现的结果和数据解释。此外, TPC将领导SMAT网络ELSI研究，以阐明人体组织中ELSI特有的因素 为体细胞嵌合体研究捐款。为了能够对这些因素进行更广泛的分析，SMAT 网络ELSI研究将包括对组织请求者(TRs)和家庭决策者(FDM)的评估。 总体而言，我们的TPC团队致力于为SMAT网络计划建立无与伦比的TPC，以 支持推进体细胞嵌合体研究，相关的ELSI因子，并最终 开发治疗由体细胞嵌合体遗传变异引起的疾病的新临床方法 在人体组织中。 相关性： 人体组织中的体细胞嵌合体(SMAHT)网络项目将提供第一个全面的 分析这三种人体组织中体细胞嵌合体引起的遗传变异的公共资源 发育层次。SMAHT网络计划将创建一个新的、最先进的研究资源，以 支持由体细胞基因组推动的生物学和疾病机制方面的新发现 人类组织的改变，并促进开发新的临床方法来治疗由 体细胞遗传变异。 OMB编号0925-0001/0002(批准的第03/2020版至2023年2月28日)续页格式页

Program Director/Principal Investigator (Bell, Thomas, J.): Project Summary: The Somatic Mosaicism across Human Tissues (SMaHT) network project will establish the first comprehensive public resource correlating genetic variation due to somatic mosaicism in human tissues from all development layers in the human body. The SMaHT Network will have multiple centers to support the advancement of three primary initiatives: 1) somatic variant discovery, 2) data analysis and network organization, and 3) technology and tool development. The data from the SMaHT network project will provide an unparalleled research resource for investigators to gain new insights on genetic variation due to somatic mosaicism processes in healthy human tissues. In addition to capitalizing on new emerging methodologies to study somatic mosaicism in human tissues, the SMaHT program includes an Ethical, Legal, Social Implications (ELSI) study to further our understanding of the ELSI factors in human tissue donation for somatic mosaicism research. To support the advancement of the SMaHT network project, this proposal will establish a Tissue Procurement Center (TPC) that will provide the SMaHT network with multiple, high quality human tissue samples from the same individual across all three developmental layers for their experimental analysis. To meet the challenges for SMaHT network, our proposal is utilizing a multi-institutional effort with extensive expertise in human tissue collection, research, pathology, imaging, biobanking, and ELSI study analysis. This span of expertise is essential for the TPC to successfully deliver well-annotated, suitable tissue samples to support the generation of reliable and reproducible results and data interpretations from the SMaHT network experimental procedures. In addition, the TPC will lead the SMaHT network ELSI study to shed light on the ELSI-specific factors in human tissue donation for somatic mosaicism research. To enable a more extensive analysis of these factors, the SMaHT network ELSI study will include evaluations on Tissue Requesters (TRs) and Family Decision Makers (FDMs). Collectively, our TPC team is committed to establishing an unequaled TPC for the SMaHT network program to support the advancement of somatic mosaicism research, the associated ELSI factors, and ultimately the development of new clinical approaches to treat disorders driven by genetic variations from somatic mosaicism in human tissues. Relevance: The Somatic Mosaicism across Human Tissues (SMaHT) network project will provide the first comprehensive public resource of analyzing genetic variation due to somatic mosaicism in human tissues from all three developmental layers. The SMaHT network program will create a new, state-of-the-art research resource to support new discoveries in the biology and disease mechanisms that are propelled by somatic genomic alterations in human tissues and facilitate the development of new clinical approaches for disorders derived from somatic genetic variations. OMB No. 0925-0001/0002 (Rev. 03/2020 Approved Through 02/28/2023) Page Continuation Format Page