ImmGen: a gene expression compendium for immune cells

拟议的资源将产生，一个完整的微阵列解剖基因表达的小鼠 免疫系统，集中于离体原代细胞，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， 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、嗜中性粒细胞）和免疫相关基质。全基因 将通过高通量微阵列技术从这些RNA获得表达谱。此外，本发明还提供了一种方法， 我们将从一组48个近交系中产生T和B淋巴细胞、Treg和NK细胞的表达谱 小鼠品系和分离杂交动物（F2和异质原种小鼠），提供了独特的 在小鼠物种的基因组变异的观点。我们将使用这些数据来定义连通性 在基因和免疫系统运作中发生的调节相互作用之间， 复杂的计算工具，已被证明是非常强大的微生物系统;我们将确定“基因” 标记”，其表征淋巴谱系和通过分化步骤的进展。的 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效应物引入小鼠干细胞或胚胎。 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，评估和部署新的可视化分析交互方法，使用 来自科学可视化领域的复杂图形词汇表。这个资源应该证明非常 有助于支持正常和病理免疫系统的研究。我们将使用高通量 基因组学、生物信息学和计算机图形技术，以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。这将为建立一个 探索免疫和自身免疫疾病。

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.