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

项目负责人/主要研究者（Bell，托马斯，J.）： 项目摘要： 跨人类组织的体细胞镶嵌（SMaHT）网络项目将建立第一个全面的 公共资源相关的遗传变异，由于体细胞镶嵌在人体组织从所有发展 在人体内的层。SMaHT网络将拥有多个中心，以支持三个 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 对于研究人员来说，由于健康人的体细胞嵌合过程， 组织中除了利用新出现的方法来研究人体组织中的体细胞嵌合现象外， SMaHT计划包括一项伦理、法律的、社会影响（ELSI）研究，以进一步了解 ELSI因子在体细胞嵌合体研究中的应用 为了支持SMaHT网络项目的推进，本提案将建立组织采购 该中心（TPC）将为SMaHT网络提供多个高质量的人体组织样本， 同一个体跨越所有三个发育层进行实验分析。迎接挑战 对于SMaHT网络，我们的建议是利用在人体组织方面具有广泛专业知识的多机构努力 收集、研究、病理学、成像、生物库和ELSI研究分析。这种专业知识的跨度是必不可少的 TPC成功地提供注释良好的合适组织样本，以支持生成可靠的 以及来自SMaHT网络实验程序的可再现结果和数据解释。此外，本发明还提供了一种方法， TPC将领导SMaHT网络ELSI研究，以阐明人体组织中ELSI特异性因子 捐赠给体细胞镶嵌研究为了更广泛地分析这些因素，SMaHT 网络ELSI研究将包括对组织决策者（TR）和家庭决策者（FDM）的评估。 总的来说，我们的TPC团队致力于为SMaHT网络计划建立无与伦比的TPC， 支持体细胞镶嵌研究的进展，相关的ELSI因素，并最终 开发新的临床方法来治疗由来自体细胞嵌合体的遗传变异驱动的疾病 在人体组织中。 相关性： 跨人类组织的体细胞镶嵌（SMaHT）网络项目将提供第一个全面的 公共资源分析遗传变异，由于人体组织中的体细胞嵌合体，从所有三个 发展层次。SMaHT网络计划将创建一个新的，最先进的研究资源， 支持生物学和疾病机制的新发现，这些发现是由体细胞基因组学推动的。 在人体组织中的改变，并促进新的临床方法的发展， 体细胞遗传变异 OMB编号0925-0001/0002（修订版03/2020批准至02/28/2023）页码继续格式页码

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