ImmGen: a gene expression compendium for immune cells

ImmGen：免疫细胞基因表达纲要

• 批准号: 7320020
• 负责人: CHRISTOPHE O. BENOIST
• 金额: $ 96.59万
• 依托单位: JOSLIN DIABETES CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-18 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7320020
• 关键词: Adopted; Animals; Autoimmune Diseases; B-Lymphocytes; Binding; Bioinformatics; Biological Phenomena; Biomedical Engineering; Boston; CD4 Positive T Lymphocytes; Cell Lineage; Cell Separation; Cells; Collaborations; Complex; Computer Graphics; Computer Simulation; Condition; Data; Data Analyses; Data Set; Development; Diabetes Mellitus; Disruption; Dissection; Electronics; Embryo; Engineering; Facility Construction Funding Category; Family; Foundations; Gene Expression; Gene Expression Microarray Analysis; Gene Expression Regulation; Generations; Genes; Genetic; Genetic Variation; Genome; Genomics; Goals; Homeostasis; Human; Imagery; Immune; Immune system; Immunologist; Immunology; Inbred Strains Mice; Internet; Investigation; Knock-out; Laboratories; Lentivirus Vector; Location; Lymphocyte; Lymphoid; Lymphoid Cell; Measures; Mediator of activation protein; Meta-Analysis; Methods; Microarray Analysis; Mind; Molecular Profiling; Monoclonal Antibody R24; Mouse Strains; Mus; Myelogenous; Natural Killer Cells; Ontology; Operative Surgical Procedures; Organ; Pathway interactions; Pattern; Pattern Recognition; Phenotype; Population; Preparation; Proteomics; Protocols documentation; RNA; RNA Interference; Regulator Genes; Research; Research Personnel; Resources; Sampling; Site; Speed; Staging; Stem cells; Structure; Suggestion; System; Techniques; Technology; Testing; Tissues; Transgenic Organisms; Universities; Variant; Visual; Visual system structure; Vocabulary; cell preparation; cell type; cohort; complement deficiency; computer science; computerized data processing; computerized tools; cost; gene interaction; grasp; in vivo; knockout animal; knockout gene; macrophage; medical schools; microbial; network models; neutrophil; novel; programs; response; tool; transcription factor; young adult

DESCRIPTION (provided by applicant): The proposed resource will generate a complete microarray dissection of gene expression in the mouse immune system, focused on primary cells ex vivo, in basal conditions or in response to genetic or environmental perturbations. A group of immunology experts will prepare, under standardized conditions, RNA from 175 populations of the innate and adaptive immune systems. These will include all lymphoid cell types, their precursors, and their variants in lymphoid organs and in different tissues, as well as the main myeloid lineages (DC, macrophages, neutrophils) and immunologically relevant stroma. Genome-wide expression profiles will be obtained from these RNAs by high-throughput microarray technology. In addition, we will generate expression profiles for T and B lymphocytes, Treg and NK cells from a panel of 48 inbred mouse strains, and segregating intercross animals (F2 and Heterogeneous Stock mice), providing a unique perspective on genomic variability in the Mus species. We will use these data to define the connectivity between genes and the regulatory interactions that occur in the operation of the immune system, using sophisticated computational tools that have proven very powerful in microbial systems; we will identify "gene signatures" that characterize lymphoid lineages and the progression through differentiation steps. The computational predictions will then be tested/validated by modulating the expression of key genes by RNA interference, using lentiviral vectors to introduce RNAi effectors into mouse stem cells or embryos. The compendium of expression profiles, strain variability and the description of genomic networks and signatures will be made publicly accessible via electronic means, with rapid data release on the ImmGen site. In addition, we will develop, evaluate and deploy novel interactive methods for visual analysis, using sophisticated graphic vocabularies from the scientific visualization field. This resource should prove very useful to support investigations of the normal and pathological immune system. We will use high-throughput genomic, bioinformatic and computer graphic technologies to determine, uniformly and reliably, the complete profiles and regulation of gene activity in the immune system. This will form an essential foundation for the exploration of immune and autoimmune diseases.

描述（由申请人提供）：所提议的资源将生成小鼠免疫系统中基因表达的完整微阵列解剖，重点关注离体、基础条件下或对遗传或环境扰动的反应的原代细胞。一组免疫学专家将在标准化条件下从 175 个先天性和适应性免疫系统群体中制备 RNA。这些将包括所有淋巴样细胞类型、其前体细胞及其在淋巴器官和不同组织中的变体，以及主要的骨髓谱系（DC、巨噬细胞、中性粒细胞）和免疫相关基质。通过高通量微阵列技术从这些 RNA 中获得全基因组表达谱。此外，我们还将生成来自 48 个近交系小鼠品系的 T 和 B 淋巴细胞、Treg 和 NK 细胞的表达谱，并分离杂交动物（F2 和异质小鼠），为小鼠物种的基因组变异性提供独特的视角。我们将使用这些数据来定义基因之间的连接性以及免疫系统运行中发生的调节相互作用，使用在微生物系统中已被证明非常强大的复杂计算工具；我们将识别表征淋巴谱系和分化步骤进展的“基因特征”。然后，通过 RNA 干扰调节关键基因的表达，使用慢病毒载体将 RNAi 效应子引入小鼠干细胞或胚胎中，来测试/验证计算预测。表达谱、菌株变异性以及基因组网络和特征描述的概要将通过电子方式向公众开放，并在 ImmGen 网站上快速发布数据。此外，我们将使用科学可视化领域的复杂图形词汇来开发、评估和部署用于视觉分析的新颖交互方法。该资源对于支持正常和病理免疫系统的研究非常有用。我们将使用高通量基因组、生物信息学和计算机图形技术来统一、可靠地确定免疫系统中基因活性的完整概况和调控。这将为探索免疫和自身免疫疾病奠定重要基础。