Pediatric Biospecimen Procurement Center (BPC) Supporting the Developmental Gene Expression (dGTEx) Project

项目主任/首席调查员(托马斯·贝尔，J.)： 项目总结： 加速整个儿科研究领域的科学发现需要推进我们的 目前对人类所有健康组织中独特的分子图谱和生理学的了解 尸体。发育基因型-组织表达(DGTEx)项目将建立第一个全面的 儿科各主要器官组织中相关基因表达与遗传变异的公共资源 人体内的系统。该项目将从四种不同的组织类型中确定约30种不同组织的分子图谱 发育组：出生后早期、儿童早期、青春期前和青春期后。DGTEx将利用 关于新的新兴方法，以获取对发育中的大脑的详细评估，并包括以下选项 多个组织的单细胞分析。促进我们对道德、法律和社会影响的理解 (ELSI)在儿科组织捐赠方面，dGTEx还包括一项ELSI研究，以分析这些因素。 来自dGTEx的数据将为临床医生和科学家提供无与伦比的研究资源，以获得新的见解 关于指导健康组织发育的调控过程的分子里程碑。支持 为了推进dGTEx，这项提议将建立儿科生物谱系采购中心(BPC)，以 为儿科实验室数据分析收集中心(LDACC)提供合适的组织样本 分析。我们的建议包括在儿科康复方面拥有广泛专业知识的多机构努力， 研究、病理学、成像、生物库、脑研究和尖端分子技术，如Single 细胞分析。我们BPC恢复团队的目标将由以下各方共同努力来实现：1)国家 疾病研究交流(NDRI)提供项目管理和协调恢复收集 TSS网络的努力，2)费城儿童医院(CHOP)处理、存储和协调 所有非脑组织的病理回顾和管理生物信息学工作流程，以及3)神经生物库，位于 马里兰大学(NBB-马里兰)对大脑进行处理、存储和提供病理检查。这一广度 专业知识对于BPC提供注解良好的、合适的生物标本至关重要，以使 LDACC的尖端实验方法和严格的数据解释得出了可重复性的结果。 提高我们对儿科组织捐赠中ELSI特有挑战的理解是一项尚未得到满足的需求 研究社区。为了能够对这些挑战进行更全面的分析，约翰霍普金斯儿童基金会 医院(JHACH)将协调dGTEx ELSI研究，以包括对组织请求者(TRs)和 已故和高危儿童的家庭决策者(FDM)。总体而言，我们的BPC团队致力于 为dGTEx项目开发一个包罗万象、无与伦比的BPC，以推动 儿科研究，ELSI挑战，以及治疗儿科疾病的新临床方法的开发。 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: Accelerating scientific discoveries across the entire spectrum of pediatric research requires advancing our current understanding of the unique molecular profiles and physiologies in all healthy tissues across the human body. The developmental Genotype-Tissue Expression (dGTEx) project will establish the first comprehensive public resource correlating gene expression and genetic variation in pediatric tissues from all major organ systems in the human body. This project will identify the molecular profiles in ~30 distinct tissue types from four developmental groups: Early post-natal, Early childhood, Pre-pubertal, and Post-pubertal. dGTEx will capitalize on new emerging methodologies to capture detailed evaluations on the developing brain and include options for single cell analysis on multiple tissues. To advance our understanding of the Ethical, Legal, Social Implications (ELSI) in pediatric tissue donation, dGTEx also includes an ELSI study to analyze these factors. The data from dGTEx will provide an unrivaled research resource for clinicians and scientists to gain new insights on the molecular milestones of regulatory processes that direct the development of healthy tissues. To support the advancement of dGTEx, this proposal will establish the pediatric Biospecimen Procurement Center (BPC) to provide the pediatric Laboratory Data Analysis Collection Center (LDACC) with suitable tissue samples for their analysis. Our proposal includes a multi-institutional effort with extensive expertise in pediatric recoveries, research, pathology, imaging, biobanking, brain research, and cutting-edge molecular techniques, such as single cell analysis. The objectives for our BPC recovery team will be led by a collaborative effort amongst: 1) National Disease Research Interchange (NDRI) to provide project management and coordinate the recovery collection effort from a network of TSS, 2) Children's Hospital of Philadelphia (CHOP) to process, store, and coordinate pathological review of all non-brain tissues and manage the bioinformatics workflow, and 3) NeuroBiobank at University of Maryland (NBB-Maryland) to process, store, and provide pathological review of brains. This breadth of expertise is essential for the BPC to provide well-annotated, suitable biospecimens to enable reliable and reproducible results from the LDACC's cutting-edge experimental methods and rigorous data interpretations. Improving our understanding of ELSI-specific challenges in pediatric tissue donation is an unmet need for the research community. To enable a more complete analysis of these challenges, Johns Hopkins All Children's Hospital (JHACH) will coordinate the dGTEx ELSI study to include evaluations of Tissue Requesters (TRs) and Family Decision Makers (FDMs) of Deceased and At-Risk Children. Collectively, our BPC team is committed to developing an all-encompassing, unparalleled BPC for the dGTEx project to empower the advancement of pediatric research, ELSI challenges, and the development of new clinical approaches to treat pediatric disorders. OMB No. 0925-0001/0002 (Rev. 03/2020 Approved Through 02/28/2023) Page Continuation Format Page