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 这是建立非人类灵长类动物发育基因型 - 组织表达（NHP DGTEX）的提议 研究中心，由俄勒冈州国家灵长类动物研究中心（ONPRC）的科学家开发，麻省理工学院， 布罗德学院和耶鲁大学。该中心将为NIH DGTEX计划提供重要资源 产生两个物种非人类灵长类动物（NHP）资源，具有许多好处，包括访问 产前发育阶段和发展表达计划进化分析的基础。 对于此提案，我们选择从两种物种中生成数据：Macaca Mulata（Rhesus Macaque），一种旧 世界猴子和新世界猴子的Callithrix Jacchus（普通Marmoset）。我们将创建一个组织 在这两个物种的6个发育阶段采样的30种不同组织类型的资源，分析总计 在此过程中的198只动物中。使用参考组织资源，我们将执行转录组测序 以及对单细胞和散装组织的其他基因组分析。为了构成RNA-Seq分析的强大基础，我们 首先从每个物种的组织面板生成全转录测序，将用于 注释基因模型。对于每个物种，我们将从 12个人，从6个时间点采样。我们建议使用多组SNRNA+ATAC测序生成 每个物种的第一代单细胞地图集，涵盖了20个总时间安排，特别强调了 脑。这些RNA-seq资源将通过Chip-Seq和Hi-的战略表观遗传学分析完成。 C用于功能元素的注释。最后，专业技术将用于从 最小的产前阶段。我们将调整Broad Institute的GTEX RNA-seq分析管道以适应 规格特定的信息和生物学，并使用所得管道分析散装RNA-seq和 执行EQTL映射。我们建议为单细胞图书馆开发一个公共交互式平台 启用探索性数据分析，假设检验和跨物种的比较。我们将使用我们的专业知识 在比较基因组学中以识别进化约束的表达模式和功能元素， 以及人类特定的特征，并研究这些特征与人类疾病的关系。我们将 创建项目中所有NHP组织的可搜索清单，并将NHP数据类型标准化为 匹配人类DGTEX规格。支持有关资源可用性和实验性的沟通 结果，该中心将将NHP数据和组织清单数据库集成到主要DGTEX门户 由Broad Institute生成和维护。该项目的成功完成将创造一个独特的 资源完成了全面的NHP生物测量存储库，该存储库涵盖成人早期的早期生活，并且 相应的基因组数据库将被广泛访问，这将提供基础和 多项未来研究的基础设施。