ImmGen: gene expression and regulation in immune cells

免疫基因组计划(ImmGen)是一个由免疫学和计算生物学实验室组成的协作小组，他们在当前的资助期间使用了严格的数据生成和QC管道，彻底剖析了小鼠免疫系统中&gt；250定义的细胞群体中的基因表达及其调控。这些数据被用来计算定义共同调节的基因模块，并预测可能的调节因子。ImmGen数据已经成为免疫学社区的重要资源，经常访问网络和智能手机支持。拟议的延续将利用ImmGen集团的集体力量。它将完善现有的概要(缺失或最近描述的种群，细胞迁移时的转录组变化)。联盟实验室将分析对一系列分子触发因素(疫苗、佐剂、肠道微生物、超级抗原、TLR配体、过敏挑战)的反应：在无法识别的靶细胞中是否有反应，转录激活如何在系统范围内产生二次共振？图谱还将扩展到非编码的mlRNAs和lincRNAs，并应用高通量RNA测序来增强和提炼微阵列数据。此外，我们将建立在我们对调控网络的计算分析的基础上，验证和加强这些预测，并评估它们的分子基础。通过测序检测到的染色质免疫沉淀(ChlP-seq)将被用来将表达谱与潜在的染色质结构、Pol-11的负载以及DNA甲基化联系起来，已经在ImmGen中描述了一组30种细胞类型。这将为研究体内原代细胞中的染色质/转录关系提供一个独特的视角。我们还将与国际基因敲除小鼠项目(KOMP)合作，分析200只KG动物的转录变化及其免疫学后果。其中50个将被选择作为我们现有研究预测的关键节点的转录因子(TF)的靶标；作为补充，这些TF的基因组位置将由Genentech的合作者通过ChlP-seq绘制出来。ImmGen数据和元数据在免疫学研究中服务于需要并被广泛使用。这一重要资源将得到维护和管理，扩大现有的几种浏览模式，以支持更复杂的用户查询和数据请求，丰富所提供的数据及其连通性。智能手机/平板电脑信息空间将继续得到支持，丰富了在本地提供的内容或可通过在线查询寻址的内容。

The Immunological Genome Project (ImmGen) is a collaborative group of immunology and computational biology laboratories who have performed in current grant period using a rigorous data generation and QC pipeline, a thorough dissection of gene expression and its regulation in >250 defined cell populations of the mouse immune system. These data were used to computationally define co-regulated gene modules and predict putative regulators. ImmGen data have become an important resource for the immunology community, with frequently consulted web and smartphone supports. The proposed continuation will harness the collective strengths of the ImmGen group. It will complete the existing compendium (missing or recently described populations, transcriptome changes upon cell migration). Consortium labs will analyze the response to a panel of molecular triggers (vaccination, adjuvants, gut microbes, super-antigens, TLR ligands, allergic challenge): are there responses in un-recognized target cells, how does transcriptional activation resonate secondarily system-wide? The profiling will also extend to non-coding mlRNAs and lincRNAs, and apply high-throughput RNA-sequencing to augment and refine the microarray data. In addition, we will build on our computational analyses of regulatory networks, validating and strengthening these predictions, and assessing their molecular underpinning. Chromatin immunoprecipitation detected by sequencing (ChlP-seq) will be used to relate the expression profiles to the underlying chromatin structure, loading with Pol-ll, and DNA methylation, in a set of 30 cell types already profiled in ImmGen. This will provide a unique perspective on chromatin/transcription relationships in primary cells in vivo. We will also collaborate with the international Knockout Mouse Project (KOMP) to analyze transcriptional changes and their immunological consequences in a panel of 200 KG animals. 50 of these will be chosen to target transcription factors (TFs) predicted to be essential nodes by our existing studies; in complement, the genomic locations of these TFs will be mapped by ChlP-seq by collaborators at Genentech. ImmGen data and meta-data serve a need in Immunology research and are widely used. This important resource will be maintained and curated, expanding the several browsing modes already in place to support more complex user queries and data requests, enriching the data presented and its connectivity. The smartphone/tablet information space will continue to be supported, enriching the content served locally or addressable through on-line queries.