Developmental GTEx Laboratory, Data Analysis and Coordination Center

GTEx发展实验室、数据分析与协调中心

• 批准号: 10662497
• 负责人: KRISTIN ARDLIE
• 金额: $ 311.62万
• 依托单位: BROAD INSTITUTE, INC.
• 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/10662497
• 关键词: 21 year old; ATAC-seq; Adolescence; Adult; Affect; Age; Anatomy; Autopsy; Biological Assay; Biology; Brain; Cell model; Cells; Cellular Assay; Childhood; Collaborations; Communities; Compensation; Complex; Computational Biology; Computing Methodologies; Consent; Data; Data Analyses; Development; Developmental Process; Disease; Disease susceptibility; Elements; Ensure; Epigenetic Process; Gene Expression; Genes; Genetic; Genetic Diseases; Genetic Transcription; Genetic Variation; Genome; Genomics; Genotype-Tissue Expression Project; Goals; Heart; Human; Human Cell Line; Human Development; Human Genetics; Immune; Individual; Investments; Laboratories; Link; Logistics; Lung; Maps; Masks; Measures; Mediation; Methods; Modeling; Molecular; Molecular Profiling; Multiomic Data; Nucleic Acid Regulatory Sequences; Process; Production; Protocols documentation; Proxy; Quantitative Trait Loci; RNA; RNA Splicing; Regulation; Regulator Genes; Regulatory Element; Research; Resolution; Resources; Sample Size; Sampling; Science; Specificity; Structure; Technology; Time; Tissue Sample; Tissues; Untranslated RNA; Variant; Work; XCL1 gene; biobank; cell type; computerized tools; cost; data integration; data management; data sharing; epigenomics; gene regulatory network; genetic analysis; genetic variant; genome wide association study; human disease; human tissue; innovation; interest; meetings; model organism; multiple omics; operation; postnatal; postnatal development; postnatal human; preservation; programs; rare variant; scaffold; single cell technology; single nucleus RNA-sequencing; spatial relationship; spatiotemporal; trait; transcriptome; transcriptome sequencing; transcriptomics

ABSTRACT Understanding the transcriptional programs governing cell identity and function is key to many outstanding questions in biology and biomedicine. Most variants associated with common diseases and traits lie in non- coding, regulatory regions of the genome, and to interpret their function, we need to identify the genes they affect and how those are expressed in the different cells of a tissue within individuals, and quantify how their expression varies across individuals. How these mechanisms are regulated during human development remains poorly understood, and most studies to date have relied on human cell lines or model organisms as proxies. GTEx did not profile tissues from postnatal stages of human development. Regulatory elements and gene networks are highly cell type–specific, and may only be active during precise developmental stages, during which they may also contribute to disease susceptibility. Thus, there is a critical need for measuring the transcriptional and regulatory landscape of tissues and cell types during human development. We will serve as the LDACC for the creation of the developmental GTEx (dGTEx) resource. (1) We will work with the BPC to establish a biobank of 30 tissues from each of 120 human postnatal postmortem donors, consented for broad research use and data sharing. (2) We will select 4 tissues of importance for common diseases, and in which there is tissue remodelling during development - brain, gut, lung and heart. We will profile these tissues with multiple single cell assays including snRNA-seq, multiomic RNA/ATAC, and spatial transcriptomics to create deep molecular maps for variant characterization. (3) We will perform baseline molecular profiling of genome sequence and bulk transcriptome for all samples, and integrate the resource with GTEx. We will use these collective data to identify e/sQTLs; create maps of element-gene relationships across tissues; chart differentiation hierarchies within tissues and across age ranges; nominate cell types in which a set of variants manifest; and map cellular and spatial relationships among cells, cellular programs, and tissue features. This project brings together a team with expertise in human genetics, production science (GTEx, ENCODE), computational biology, single cell technologies, and common disease genetics. We will create a data and biospecimen resource for the scientific community that will underpin studies to understand cellular and tissue changes during human development, genome regulation, and common disease variant interpretation.

抽象的 了解控制单元格身份和功能的转录程序是许多杰出的关键 生物学和生物医学的问题。与常见疾病和特征相关的大多数变体都在于非 - 编码，基因组的调节区域以及解释其功能，我们需要确定它们影响的基因 以及它们如何在个体内部组织的不同细胞中表达，并量化其表达方式 各个人的多样性。在人类发展期间如何调节这些机制的方式仍然很差 理解，迄今为止，大多数研究都依赖于人类细胞系或模型生物作为代理。 GTEX做到了 不是人类发育后阶段的组织。监管元素和基因网络是 高度细胞型特异性，并且只能在精确的发育阶段处于活动状态，在此期间 也有助于疾病的易感性。那是衡量转录和 人类发育过程中组织和细胞类型的调节景观。 我们将作为创建发展GTEX（DGTEX）资源的LDACC。 （1）我们会的 与BPC合作，建立来自120个人类后死后供体中每一个组织的30个组织的生物库， 同意进行广泛的研究用途和数据共享。 （2）我们将选择4种重要性的组织 疾病，在发育过程中进行组织重塑 - 大脑，肠道，肺和心脏。我们将概括 这些时机具有多个单细胞测定法，包括snRNA-seq，多组分RNA/ATAC和空间 转录组学创建深层分子图以进行变异表征。 （3）我们将执行基线 所有样品的基因组序列和批量转录组的分子分析，并将资源与 GTEX。我们将使用这些集体数据来识别E/SQTL；在跨越元素 - 基因关系的地图 组织；图表分化的层次结构和跨年龄范围；提名的单元类型 变体的表现；以及细胞，细胞程序和组织之间的细胞和空间关系 特征。 该项目汇集了一个具有人类遗传学专业知识的团队，生产科学（GTEX， 编码），计算生物学，单细胞技术和常见疾病遗传学。我们将创建一个数据 和科学界的生物循环资源，这些资源将了解细胞和组织 人类发育，基因组调节和常见疾病变异解释的变化。