ImmGen: Gene Expression and Regulation in Immune Cells

IMmGen是一个由19个免疫学和计算生物学实验室组成的合作小组， 在标准化条件下，彻底剖析免疫中的基因表达及其调节 鼠标的系统。共享的SOP、数据生成和处理管道为跨 可比较的基因表达和表观遗传学数据，作为经常咨询的公共资源和 参考资料。已经开发了机器学习方法来推断潜在的基因调控网络。 这些主要主题将继续下去：1，绘制抄本。我们将继续推动ImmGen的发展 基因表达纲要，结合群体RNAseq和单细胞RNAseq/CITEseq来绘制 免疫细胞横跨淋巴和实质器官的景观，世系对生物体的共同适应 地理位置、传染病/自身免疫挑战、遗传变异或特定性别变异。我们将扩大正在进行的 所有主要血统的细胞因子签名目录。绘制“暗转录组”(未被识别) 转录本或剪接变异体从标准参考文献中缺失)，长读直接RNA测序将是 在基线或强激活后应用。2、绘制免疫基因组调控网络图。我们会 进一步的ImmGen的表观基因组图谱：(I)正在进行的组蛋白翻译后高颗粒图谱 修改代码将扩展到揭示代码的微妙方面的非标准PTM 实施；(2)我们将生成跨谱系的全基因组甲基组谱；(3)多模式 在单个细胞(SHAREseq)中匹配染色质可及性和mRNA的策略将应用于 包含表型变异范围的特定谱系(T、B、ILC、髓系)的细胞的“桶” 在一个谱系内，通过使用F1杂交小鼠作为供体进行内部验证，将Tf-1基因变异联系起来。 结合染色质激活的基序。这些多层数据将作为正在进行的人工智能的输入 免疫细胞分化基础调控网络的智能解码。3：从数据到公共 参考资料。ImmGen数据作为社区参考的作用将会扩大。互动型 ImmGen Web和智能手机应用程序上的数据库行将得到扩展和优化(以单元格为中心 查询，RNA-蛋白质匹配)。以参考数据同质性为主旨，我们将导入和协调 多模式免疫基因组数据集的集合，对内部产生的数据进行补充。这 同源资源将用于方便公众浏览，并将支持：(I)免疫的定义 基于统计上客观的基于距离和连续性的标准的细胞类型(II)参考图(交叉 器官或交叉谱系)以供公众使用，新的研究可通过标记转移软件进行比对， 具有专门的在线服务(Iii)识别细胞类型或共调控基因的表达签名面板 模块。这项参考工作将通过主持的电子邮件征求社区反馈和参与 论坛。为了实现便捷的计算和重用，我们将部署基于云的ImmGen数据访问(Terra)。

ImmGen is a collaborative group of 19 Immunology and Computational Biology laboratories who perform, under standardized conditions, a thorough dissection of gene expression and its regulation in the immune system of the mouse. Shared SOPs, data generation and processing pipelines have made for cross- comparable gene expression and epigenetic data that serve as frequently consulted public resource and reference. Machine learning approaches have been developed to infer underlying genetic regulatory networks. These main themes will be continued: 1, Charting Transcriptomes. We will continue to evolve the ImmGen gene expression compendium, combining population RNAseq with single-cell RNAseq/CITEseq to chart the landscape of immunocytes across lymphoid and parenchymal organs, lineage co-adaptation to organismal locations, infectious/autoimmune challenges, or genetic or sex-specific variation. We will expand the ongoing catalog of cytokines signatures in all the major lineages. To chart the “dark transcriptome” (unrecognized transcripts or splice variants missing from standard references), long-read direct RNA sequencing will be applied, at baseline or after strong activation. 2, Charting Immunogenomic Regulatory Networks. We will further ImmGen’s epigenomic charting: (i) ongoing highly granular mapping of the histone post-translational modification code will be expanded to non-standard PTMs that reveal subtle aspects of the code’s implementation; (ii) we will generate genomewide methylome profiles across lineages; (iii) multimodal strategies that match chromatin accessibility and mRNA across single-cells (SHAREseq) will be applied in “buckets” of cells of a given lineage (T, B, ILC, myeloid) that encompass the range of phenotypic variation within a lineage, internally validated by using F1 intercross mice as donors, relating genetic variation in TF- binding motifs with chromatin activation. These multilayered data will serve as input for ongoing Artificial Intelligence decoding of regulatory networks underlying immunocyte differentiation. 3: From Data to Public Reference. The role that ImmGen data serve as a community reference will be broadened. The interactive databrowsers on the ImmGen web and smartphone app will be expanded and optimized (cell-type centered querying, RNA-protein match). With the leitmotiv of reference data homogeneity, we will import and harmonize a collection of multimodal immunogenomic datasets, complementing those produced internally. This homogenous resource will be served for facilitated public browsing, and will support: (i) definitions of immune cell-types based on statistically objective distance- and continuity-based criteria (ii) Reference Maps (cross- organ or cross-lineages) for public use, against which new studies can be aligned by label transfer software, with a dedicated online service (iii) panels of expression signatures identifying cell-types or co-regulated gene modules. This reference work will solicit community feedback and participation via moderated electronic forums. To enable facile computation and re-use, we will deploy cloud-based ImmGen data access (Terra).