Research Resources: Epigenomic and Transcriptomic Profile of Human Immune Cells

项目摘要 虽然大量的遗传变异与人类疾病的风险有关，但这些变异是如何产生的？ 影响各种细胞类型中基因表达的变异在很大程度上仍是未知的。为了弥补这一差距， 免疫细胞，以及确定哪些免疫细胞类型最容易受到疾病的影响- 风险变异，DICE（免疫细胞表达数据库，表达数量性状基因座（eQTL）和 表观基因组学）项目成立于2014年，由目前的R24资源赠款（R24 AI 108564）资助。我们 目前的数据集揭示了疾病风险相关的SNP对常见免疫细胞类型的影响（http：//dice-cn. org/cn/cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn-cn database.org）。然而，这个数据集还远未完成;疾病风险变异对几个非常重要的基因的影响， 重要但罕见和/或难以分离的细胞，如循环先天免疫细胞和组织驻留细胞， 免疫细胞，还有待研究。在完成了第一笔DICE赠款的目标后，我们现在建议 通过以下具体目标建立我们的研究结果：在目标1中，我们将eQTL分析扩展到（A）稀有 循环免疫细胞类型，例如树突状细胞、先天性淋巴样细胞（ILC）、不变NKT细胞、gdT细胞 和CD 4-CTL亚群，分离自库中冷冻保存的白细胞分离样品（>100）， DICE项目，（B）离体活化的循环免疫细胞，和（C）组织驻留记忆（TRM）T细胞类型 例如从100名受试者的肺组织样品中分离的CD 8 + TRM、CD 4 + TRM和组织驻留NK细胞， 绘制组织特异性免疫eQTL组织驻留免疫细胞类型。在目标2中，我们将定义远程 免疫细胞类型中增强子-启动子3D相互作用以预测功能重要的非编码GWAS SNPs。在目标3中，我们将扩展我们现有的网站（http：dice-database.org）， 产生的实验数据和分析工具提供给社区。

PROJECT SUMMARY While an enormous number of genetic variants have been associated with risk for human disease, how these variants affect gene expression in various cell types remains largely unknown. To address this gap as it relates to immune cells, as well as to identify which immune cell types are most susceptible to the effects of disease- risk variants, the DICE (Database of Immune Cell Expression, Expression quantitative trait loci (eQTLs) and Epigenomics) project was established in 2014, funded by the current R24 resource grant (R24AI108564). Our current datasets reveal the effects of disease risk-associated SNPs on common immune cell types (http://dice- database.org). However, this dataset is far from complete; the effects of disease-risk variants on several very important but rare and/or difficult to isolate cells, such as circulating innate immune cells and tissue-resident immune cells, have yet to be studied. Having accomplished the aims of the first DICE grant, we now propose to build on our findings through the following specific aims: In Aim 1, we will expand eQTL analysis to (A) Rare circulating immune cell types such as dendritic cells, innate lymphoid cells (ILCs), invariant NKT cells, gdT cells and CD4-CTL subsets, isolated from banked cryopreserved leukapheresis samples (>100) collected via the DICE project, (B) circulating immune cells activated ex vivo, and (C) Tissue-resident memory (TRM) T cell types such as CD8+ TRM, CD4+ TRM and tissue-resident NK cells isolated from lung tissue samples of 100 subjects to map tissue-specific immune eQTLs tissue-resident immune cell types. In Aim 2, we will define long-range enhancer-promoter 3D interactions in immune cell types to predict functionally important non-coding GWAS SNPs. In Aim 3, we will expand our existing website (http://dice-database.org) to make current and newly generated experimental data and analysis tools available to the community.