ImmGen: a gene expression compendium for immune cells

ImmGen：免疫细胞基因表达纲要

• 批准号: 7497011
• 负责人: CHRISTOPHE O. BENOIST
• 金额: $ 99.53万
• 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 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7497011
• 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; 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

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 vocabulaires 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.

拟议的资源将生成小鼠基因表达的完整微阵列解剖 免疫系统，专注于离体原代细胞，在基础条件下或响应遗传或 环境扰动。一组免疫学专家将在标准化条件下准备， 来自 175 个先天性和适应性免疫系统群体的 RNA。这些将包括所有淋巴细胞 类型，它们的前体，以及它们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。全基因组 将通过高通量微阵列技术从这些RNA中获得表达谱。此外， 我们将从一组 48 个近交细胞中生成 T 和 B 淋巴细胞、Treg 和 NK 细胞的表达谱 小鼠品系，并分离杂交动物（F2 和异种小鼠），提供了独特的 对Mus物种基因组变异的看法。我们将使用这些数据来定义连接性 基因与免疫系统运行中发生的调节相互作用之间的关系，使用 复杂的计算工具已被证明在微生物系统中非常强大；我们将识别“基因 特征”，表征淋巴谱系和分化步骤的进展。 然后通过 RNA 调节关键基因的表达来测试/验证计算预测 干扰，使用慢病毒载体将RNAi效应子引入小鼠干细胞或胚胎中。 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。在 此外，我们将开发、评估和部署用于视觉分析的新颖的交互式方法，使用 来自科学可视化领域的复杂图形词汇。这个资源应该证明非常 对于支持正常和病理免疫系统的研究很有用。我们将使用高通量 基因组、生物信息和计算机图形技术，统一可靠地确定完整的 免疫系统中基因活性的概况和调节。这将为 免疫和自身免疫疾病的探索。