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，彻底剖析基因表达及其在免疫中的调节， 鼠标系统共享的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数据，作为经常查阅的公共资源， 参考已经开发了机器学习方法来推断潜在的遗传调控网络。 这些主题将继续：1，图表转录组。我们会继续发展入境处 基因表达纲要，将群体RNAseq与单细胞RNAseq/CITEseq相结合， 免疫细胞在淋巴和实质器官中的分布，对生物体的谱系共适应 位置、感染/自身免疫挑战或遗传或性别特异性变异。我们将扩大正在进行的 所有主要谱系的细胞因子标签目录。绘制“暗转录组”（未识别 标准参考文献中缺失的转录物或剪接变体），将进行长读直接RNA测序。 在基线或强激活后应用。2、绘制免疫基因组学调控网络。我们将 进一步ImmGen的表观基因组制图：（i）正在进行的组蛋白翻译后 修改代码将扩展到非标准的PTM，这些PTM揭示了代码的微妙方面。 实施;（ii）我们将产生跨谱系的全基因组甲基化组谱;（iii）多模式 匹配染色质可及性和跨单细胞mRNA的策略（SHAREseq）将应用于 涵盖表型变异范围的给定谱系（T、B、ILC、髓样）的细胞“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中的遗传变异 与染色质活化的结合基序。这些多层数据将作为正在进行的人工智能的输入。 免疫细胞分化调控网络的智能解码。第三章：从数据到公众 参考ImmGen数据作为社区参考的作用将得到扩大。交互式 ImmGen网络和智能手机应用程序上的数据浏览器将得到扩展和优化（以细胞类型为中心 查询，RNA-蛋白质匹配）。在参考数据同质化的主旨下，我们将引入和协调 多模式免疫基因组学数据集的集合，补充内部产生的数据集。这 同质资源将提供方便公众浏览，并将支持：（i）免疫的定义 基于统计客观距离和连续性标准的细胞类型（ii）参考地图（交叉） 器官或跨谱系）供公众使用，新的研究可以通过标签转移软件与之对齐， （iii）鉴定细胞类型或共调节基因的表达特征组 模块。这项参考工作将征求社区的反馈和参与，通过主持电子 论坛。为了实现轻松的计算和重用，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).