ImmGen: gene expression and regulation in immune cells

免疫基因组计划（ImmGen）是一个免疫学和计算生物学实验室的合作小组，他们在当前的资助期内使用严格的数据生成和QC管道，对小鼠免疫系统中超过250个定义的细胞群中的基因表达及其调控进行了彻底的剖析。这些数据被用来计算定义共调节基因模块和预测推定的监管机构。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。建议中的延续措施，将可发挥入境处的集体力量。它将完成现有的简编（缺失或最近描述的群体，细胞迁移后的转录组变化）。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、过敏性激发）的反应：未识别的靶细胞是否有反应，转录激活如何在系统范围内产生次级共振？该分析还将扩展到非编码mlRNA和lincRNA，并应用高通量RNA测序来增加和完善微阵列数据。此外，我们将建立在我们的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（ChIP-seq）检测的染色质免疫沉淀将用于将表达谱与已经在ImmGen中分析的一组30种细胞类型中的潜在染色质结构、Pol-II加载和DNA甲基化相关联。这将提供一个独特的视角在原代细胞在体内的染色质/转录的关系。我们还将与国际敲除小鼠项目（KOMP）合作，在一组200公斤的动物中分析转录变化及其免疫学后果。其中50个将被选择用于靶向转录因子（TF），这些转录因子被我们现有的研究预测为重要节点;作为补充，这些TF的基因组位置将由Genentech的合作者通过ChIP-seq进行定位。ImmGen数据和元数据满足了免疫学研究的需求，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，丰富所呈现的数据及其连通性。将继续支持智能手机/平板电脑信息空间，丰富本地提供的或通过在线查询提供的内容。

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.