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合作小组，他们在当前的资助期内使用严格的数据生成和QC管道，对小鼠免疫系统中bbbb250个定义细胞群中的基因表达及其调控进行了彻底的解剖。这些数据用于计算定义共调控基因模块和预测假定的调控。ImmGen数据已成为免疫学社区的重要资源，经常咨询网络和智能手机支持。拟议的延续将利用imgen集团的集体力量。它将完成现有的纲要（缺失或最近描述的种群，细胞迁移时转录组的变化）。联盟实验室将分析对一组分子触发因素（疫苗接种、佐剂、肠道微生物、超级抗原、TLR配体、过敏挑战）的反应：在未识别的靶细胞中是否存在反应，转录激活如何在全系统范围内产生二次共振？分析还将扩展到非编码mlrna和lincRNAs，并应用高通量rna测序来增加和完善微阵列数据。此外，我们将建立对调控网络的计算分析，验证和加强这些预测，并评估其分子基础。通过测序（ChlP-seq）检测的染色质免疫沉淀将用于将表达谱与潜在的染色质结构，装载pol - 1和DNA甲基化联系起来，在imgen中已经分析的30种细胞类型中。这将为体内原代细胞的染色质/转录关系提供一个独特的视角。我们还将与国际敲除小鼠项目（KOMP）合作，分析200公斤动物的转录变化及其免疫学后果。我们将选择其中的50个靶向转录因子（TFs），这些转录因子被我们现有的研究预测为基本节点；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。ImmGen数据和元数据服务于免疫学研究的需要，被广泛使用。这一重要资源将得到维护和管理，扩展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，丰富所呈现的数据及其连接性。智能手机/平板电脑信息空间将继续得到支持，丰富本地服务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.