Laboratory, Data Analysis, and Coordinating Center (LDACC) for the Developmental Human Genotype-Tissue Expression Project

项目摘要 我们建议建立实验室、数据分析和协调中心(LDACC)以促进发展 基因-组织表达(DGTEx)项目，以生成、分析和集成来自 不同的组织，侧重于多个大脑区域，跨越4个年龄组：婴儿期、幼儿期、晚期 童年和青春期。我们将开发一份整合了基因分型数据和功能基因组的图谱 有助于预测非编码基因组变异对基因表达的功能影响的数据，无论是常见的还是罕见的。 我们的项目将解决两个关键的知识差距。首先，GTEx和其他财团的大规模努力已经 侧重于成人或出生前年龄，仅在有限程度上，从出生起关注出生后发育年龄 到了青春期，关键时期是因为人类有较长的后天发育，尤其突出 在大脑里。第二，在特定细胞类型的水平上的分辨率在许多研究中是缺乏的。研究产后发育 在特定细胞类型水平上的发育是至关重要的，因为遗传变异对基因调控的影响 通常是特定于细胞类型的。为了解决这些关键的知识差距，我们建议1)创建一个地图集 儿童组织基因在块状组织和单细胞群体中的表达；2)基因差异分析 表达、调节和已知的表达QTL和剪接QTL跨越出生后人类发育， 以及3)建立并提供尽可能多的组织的生物库(每个捐赠者最多50个组织)； 用于进一步表征的相关数据。4)为数据传播和整合开发一个数据门户 我们的数据与基因类型组织表达(GTEx)、脑主动细胞普查网络(BICCN)和其他 财团。通过这样做，我们将从根本上扩展GTEx早先的努力，并创建一个全面和 关于人类发育组织的广泛可用的社区资源，以帮助推动 多个研究领域，通常是任何疾病。

PROJECT ABSTRACT We propose to establish the Laboratory, Data Analysis, and Coordinating Center (LDACC) for the Developmental Genotype-Tissue Expression (dGTEx) Project to generate, analyze, and integrate multimodal genomic data from various tissues, with emphasis on multiple brain regions, across 4 age groups: infancy, early childhood, late childhood and adolescence. We will develop an atlas that integrates genotyping data and functional genomic data to help predict functional impact of noncoding genomic variants, both common and rare on gene expression. Our project will address two key knowledge gaps. First, large-scale efforts by GTEx and other consortia have focused on adult or prenatal ages and only to a limited extent, on the postnatal developmental ages from birth to adolescence, critical periods because humans have prolonged postnatal development, particularly prominent in the brain. Second, resolution at the level of specific cell types in lacking in many studies. Studying postnatal development at the level of specific cell types is critical because the effects of genetic variants on gene regulation are often cell-type specific. To address these critical knowledge gaps, we propose to 1) create an atlas of pediatric tissue gene expression in bulk tissues and single cell populations, 2) analyze differences in gene expression, regulation, and known expression QTLs and splicing QTLs across postnatal human development, and 3) create and make available a biobank of as many tissues as possible (up to 50 tissues per donor), and associated data for further characterization. 4) develop a data portal for data dissemination as well as integration of our data with Genotype Tissue Expression (GTEx), Brain Initiative Cell Census Network (BICCN) and other consortia. By so doing, we will radically expand upon earlier efforts by GTEx and create a comprehensive and broadly available community resource on human developmental tissues, to help drive research forward in multiple research fields, and generally any disease.