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)

基本信息

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
项目类别：
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

项目摘要

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开发的实验室，数据分析和协调中心（LDACC）基因型 - 组织表达（DGTEX）项目，以生成，分析和整合从中的多模式基因组数据各种组织，重点是四个年龄段的多个大脑区域：婴儿期，幼儿期，晚期童年和青春期。我们将开发一个集成基因分型数据和功能基因组的地图集数据有助于预测非编码基因组变体的功能影响，无论是常见还是在基因表达上很少见。我们的项目将解决两个关键知识差距。首先，GTEX和其他财团的大规模努力有专注于成人或产前年龄，仅在有限的程度上，从出生后出生后的发育年龄到青春期，关键时期是因为人类延长了产后发展，特别是显着的在大脑中。其次，在许多研究中缺乏特定细胞类型水平的分辨率。研究产后特定细胞类型水平的开发至关重要，因为遗传变异对基因调节的影响通常是细胞类型的特异性。为了解决这些关键的知识差距，我们建议1）创建一个地图集小儿组织基因表达在大块组织和单细胞种群中，2）分析基因差异在产后人类发育中的表达，调节和已知的表达QTL和剪接QTL， 3）创建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），并且相关数据以进一步表征。 4）开发数据门户以进行数据传播以及集成我们具有基因型组织表达（GTEX），脑启动细胞普查网络（BICCN）和其他数据的数据财团。通过这样做，我们将从根本上扩展GTEX的早期努力，并创建一个全面的和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，通常是任何疾病。