ImmGen: a gene expression compendium for immune cells

建议的资源将产生一个完整的小鼠基因表达的微阵列分析 免疫系统，主要集中在体外的原始细胞，处于基础状态或对遗传或 环境扰动。一组免疫学专家将在标准化条件下准备， 来自先天性免疫系统和获得性免疫系统的175个群体的RNA。这将包括所有淋巴样细胞 类型、它们的前体及其在淋巴器官和不同组织中的变体以及主要的 髓系(DC、巨噬细胞、中性粒细胞)和免疫相关的间质。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，并隔离杂交动物(F2和异种系小鼠)，提供独特的 小鼠物种基因组变异性的研究进展。我们将使用这些数据来定义连接性 在基因和免疫系统运行中发生的调节相互作用之间，使用 复杂的计算工具，在微生物系统中被证明是非常强大的；我们将识别“基因 特征“，描述淋巴谱系和分化过程。 然后，将通过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效应器导入小鼠干细胞或胚胎。 表达谱概要、菌株变异性以及基因组网络和签名的描述 将通过电子手段向公众开放，并在ImmGen网站上迅速发布数据。在……里面 此外，我们将开发、评估和部署用于视觉分析的新的交互方法，使用 来自科学可视化领域的复杂图形词汇表。这种资源应该被证明是非常 有助于支持对正常和病理免疫系统的研究。我们将使用高通量 基因组、生物信息学和计算机图形技术，以统一和可靠地确定完整的 免疫系统中基因活性的分布和调节。这将形成一个重要的基础 探索免疫和自身免疫性疾病。

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.