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

项目负责人/主要研究者（Bell，托马斯，J.）： 项目摘要： 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分子谱和生理学的了解 身体发育基因型-组织表达（dGTEx）项目将建立第一个全面的 所有主要器官的儿科组织中与基因表达和遗传变异相关的公共资源 人体内的系统。该项目将确定来自四个国家的约30种不同组织类型的分子谱。 发育组：出生后早期、幼儿期、青春期前和青春期后。dGTEx将利用 关于新出现的方法，以获取对发展中大脑的详细评价，并包括 多个组织的单细胞分析。提高我们对道德、法律的和社会影响的理解 在儿科组织捐献中，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 在指导健康组织发育的调节过程的分子里程碑上。支持 dGTEx的发展，该提案将建立儿科生物标本采购中心（BPC）， 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.我们的建议包括一个多机构的努力与广泛的专业知识，在儿科康复， 研究，病理学，成像，生物库，大脑研究和尖端分子技术，如单 细胞分析我们的BPC恢复团队的目标将由以下各方的合作努力领导：1）国家 疾病研究交流中心（NDRI）提供项目管理和协调恢复收集 来自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学检查并管理生物信息学工作流程，以及3）NeuroBiobank， 马里兰州大学（NBB-马里兰州）处理、存储和提供大脑病理学检查。这种广度 专业知识对于BPC提供注释良好、合适的生物标本以实现可靠且 从LDACC的尖端实验方法和严格的数据解释可重复的结果。 提高我们对ELSI在儿科组织捐献中的特定挑战的理解是一个未满足的需求， 研究社区。为了能够更全面地分析这些挑战，约翰霍普金斯所有儿童的 医院（JHACH）将协调dGTEx ELSI研究，以包括组织凝固剂（TR）的评价， 死亡和风险儿童的家庭决策者。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， 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（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: 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