Multispecies NHP dGTEx Research Center

多物种 NHP dGTEx 研究中心

• 批准号: 10460849
• 负责人: KRISTIN ARDLIE
• 金额: $ 321.64万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10460849
• 关键词: Address; Adult; Animals; Atlases; Biological Specimen Banks; Biology; Brain; Breeding; Callithrix; Callithrix jacchus jacchus; Cebidae; Cells; Cercopithecidae; ChIP-seq; Communication; Communities; Comparative Study; Complement; Data; Data Analyses; Databases; Defect; Development; Developmental Process; Disease; Dissection; Elements; Equipment and supply inventories; Fetus; Gene Expression Profile; Generations; Genes; Genetic; Genomics; Genotype; Genotype-Tissue Expression Project; Hi-C; Human; Human Development; Individual; Infrastructure; Institutes; Laboratories; Life; Macaca; Macaca mulatta; Modeling; Molecular; Oregon; Pan troglodytes; Papio; Partner in relationship; Pathology; Pattern; Positioning Attribute; Pregnancy; Primates; Process; Protocols documentation; RNA analysis; Research; Research Personnel; Resources; Rhesus; Sampling; Scientist; Small Nuclear RNA; Standardization; Techniques; Testing; Time; Tissue Sample; Tissues; Transcript; United States National Institutes of Health; Universities; XCL1 gene; analysis pipeline; animal colony; base; comparative genomics; data integration; epigenetic profiling; human disease; improved; insight; nonhuman primate; postnatal; prenatal; programs; research study; single cell analysis; tissue resource; transcriptome sequencing; transcriptomics

PROJECT SUMMARY This is a proposal to establish a Nonhuman Primate Developmental Genotype-Tissue Expression (NHP dGTEx) Research Center, developed by scientists at the Oregon National Primate Research Center (ONPRC), MIT, the Broad Institute, and Yale University. This Center will provide a vital resource to the NIH dGTEx program by generating a two-species nonhuman primate (NHP) resource with numerous benefits, including access to prenatal developmental stages and a basis for evolutionary analysis of developmental expression programs. For this proposal we have elected to generate data from two species: Macaca mulata (rhesus macaque), an old- world monkey, and Callithirix jacchus (common marmoset), a new-world monkey. We will create a tissue resource of 30 different tissues types sampled across 6 developmental stages in both species, profiling a total of 198 animals in the process. Using the reference tissue resource, we will perform transcriptome sequencing and other genomic analysis of single-cell and bulk tissues. To form a robust basis for analysis of RNA-seq, we begin by generating full-transcript sequencing from a panel of tissues of each species, which will be used for annotating gene models. For each species we will then generate bulk RNA-sequencing of 30 tissues each from 12 individuals, sampled from 6 timepoints. We propose to use multiome snRNA+ATAC sequencing to generate a first generation single-cell atlas for each species, covering 20 total tissues, with a special emphasis on the brain. These RNA-seq resources will be complemented with strategic epigenetic profiling by CHIP-seq and Hi- C for annotation of functional elements. Finally, specialized techniques will be used to generate data from the smallest prenatal stages. We will adapt the Broad Institute’s GTEx RNA-seq analysis pipeline to accommodate species-specific information and biology, and use the resulting pipelines to analyze the bulk RNA-seq and perform eQTL mapping. We propose to develop a public, interactive platform for the single-cell atlases that enables exploratory data analysis, hypothesis testing, and comparison across species. We will use our expertise in comparative genomics to identify evolutionarily constrained expression patterns and functional elements, as well as human-specific features, and investigate the relationship of these features to human disease. We will create a searchable inventory of all NHP tissues sampled in the project, and standardize NHP data types to match the human dGTEx specifications. To facilitate communicationabout resource availabilityand experimental results, the Center will integrate the NHP data and tissue inventory database into the primary dGTEx portal to be generated and maintained by the Broad Institute. The successful completionof the project will create a unique resource comprising a comprehensive NHP biospecimen repository spanning early prenatal to adult life, and a corresponding genomic database to be made widely accessible which will provide the groundwork and infrastructure for multiple future research studies.

项目摘要 这是建立非人灵长类发育基因型-组织表达（NHP dGTEx）的建议 研究中心，由科学家在俄勒冈州国家灵长类动物研究中心（ONPRC），麻省理工学院， 布罗德研究所和耶鲁大学。该中心将通过以下方式为NIH dGTEx计划提供重要资源： 产生具有许多益处的两种非人灵长类动物（NHP）资源，包括获得 产前发育阶段和发育表达程序的进化分析的基础。 对于这个提议，我们选择从两个物种中生成数据：猕猴（恒河猴），一种古老的， 世界猴，和Callithirix jacchus（普通绒猴），一种新世界猴。我们将创造一种组织 在两个物种的6个发育阶段取样的30种不同组织类型的资源， 198只动物在此过程中使用参考组织资源，我们将进行转录组测序 以及单细胞和大块组织的其他基因组分析。为了形成用于RNA-seq分析的稳健基础，我们 开始，从每个物种的一组组织中产生全转录测序，这将用于 注释基因模型。对于每个物种，我们将对每个物种的30个组织进行批量RNA测序， 12名个体，从6个时间点取样。我们建议使用多组snRNA+ATAC测序来产生 每个物种的第一代单细胞图谱，涵盖20个组织，特别强调 个脑袋这些RNA-seq资源将通过CHIP-seq和Hi- C用于功能元素的注释。最后，将使用专门的技术从 最小的产前阶段。我们将调整布罗德研究所的GTEx RNA-seq分析管道，以适应 物种特异性信息和生物学，并使用由此产生的管道来分析批量RNA-seq和 进行eQTL作图。我们建议为单细胞地图集开发一个公共的交互式平台， 支持探索性数据分析、假设检验和跨物种比较。我们将利用我们的专业知识 在比较基因组学中，以确定进化上受限制的表达模式和功能元件， 以及人类特有的特征，并研究这些特征与人类疾病的关系。我们将 创建一个项目中所有NHP组织样本的可搜索目录，并标准化NHP数据类型， 符合人体dGTEx规格促进关于资源可用性和实验性的沟通 结果，该中心将把NHP数据和组织库存数据库整合到主要的dGTEx门户网站， 由布罗德研究所生成和维护。该项目的成功完成将创造一个独特的 资源包括一个全面的NHP生物标本库，涵盖早期产前到成年生活， 相应的基因组数据库将被广泛使用，这将提供基础， 为未来多项研究提供基础设施。