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

人类发育基因型组织表达项目实验室、数据分析和协调中心 (LDACC)

• 批准号: 10709553
• 负责人: Mark Bender Gerstein
• 金额: $ 171.18万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-22 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10709553
• 关键词: Address; Adolescence; Adult; Affect; Age; Alleles; Animals; Area; Atlases; BRAIN initiative; Biologic Characteristic; Biological; Birth; Brain; Brain region; Cell Nucleus; Cells; Censuses; Childhood; Chromatin; Collaborations; Collecting Cell; Communities; Complement; Consent Forms; DNA; Data; Data Analyses; Databases; Development; Dimensions; Disease; Epigenetic Process; Funding; Gene Expression; Gene Expression Profiling; Gene Expression Regulation; Generations; Genes; Genotype; Genotype-Tissue Expression Project; Human; Human Development; Knowledge; Laboratories; Life; Link; Mammals; Measures; Modification; Monitor; Neocortex; Organ; Pattern; Population; Production; Protocols documentation; Quality Control; Quantitative Trait Loci; RNA Splicing; Recommendation; Regulation; Reporting; Research; Resolution; Resources; Review Committee; Risk; Sampling; Specimen; Spliced Genes; Standardization; System; Testing; Tissue Procurements; Tissues; Untranslated RNA; Variant; Whole Blood; age group; biobank; cell type; critical period; data dissemination; data integration; data portal; early childhood; fetal; functional genomics; genetic variant; genome sequencing; genome wide association study; genomic data; genomic locus; histopathological examination; human disease; infancy; insight; multimodal data; multimodality; multiple omics; neocortical; perinatal period; postnatal; postnatal development; postnatal human; postnatal period; prenatal; single nucleus RNA-sequencing; transcriptome; transcriptome sequencing

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.

项目摘要 我们建议建立实验室，数据分析和协调中心（LDACC）， 基因型-组织表达（dGTEx）项目，用于生成、分析和整合来自 各种组织，重点是多个大脑区域，跨越4个年龄组：婴儿期，幼儿期，晚期 儿童和青少年时期。我们将开发一个图谱，整合基因分型数据和功能基因组学数据， 数据，以帮助预测非编码基因组变异的功能影响，常见和罕见的基因表达。 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 侧重于成人或产前年龄，仅在有限程度上侧重于出生后发育年龄 到青春期，关键时期，因为人类有延长产后发展，特别突出， 在大脑中。其次，许多研究缺乏在特定细胞类型水平上的分辨率。产后学习 在特定细胞类型水平的发育是至关重要的，因为遗传变异对基因调控的影响 通常是细胞类型特异性的。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， 儿科组织基因在大块组织和单细胞群体中的表达，2）分析基因表达的差异， 表达、调控和已知的表达QTL和剪接QTL跨越出生后人类发育， 以及3）创建并提供尽可能多的组织的生物库（每个供体多达50个组织），以及 用于进一步表征的相关数据。4)开发一个数据门户，用于数据传播和整合 我们的数据与基因型组织表达（GTEx），脑倡议细胞普查网络（BICCN）和其他 财团。通过这样做，我们将从根本上扩大GTEx早期的努力，并创建一个全面的， 关于人类发育组织的广泛可用的社区资源，以帮助推动研究， 多个研究领域，一般来说，任何疾病。