[{"content":"（一）单细胞数据集 69个滑膜样本 22个肠样本 91个PBMC体外培养样本 OneK1K cohort （二）Pseudobulk cell type specific eQTL 由于作者关注HLA基因，所以只对相关的髓系细胞、T细胞、B细胞进行了分析 不同cohrt构建不同的PEERs，根据不同群体大小使用不同数量的PEERs 随后单独对每个cohort进行eQTL mapping (P \u0026lt; 4e-9)，找出每个HLA基因对应的lead eQTL，其中91.7% (88/96)具备mean directional concord-ance，证明了不同cohort间存在一致性。 最终分析得到24个与MHC关联的lead eQTL For each cohort: Eresid=βGXG+sex+age+βi(1,2,...,5)PCi(1,2,...,5)+βjPEERj+ϵ E_{resid} = \\beta_G X_G + sex + age + \\beta_{i(1,2,...,5)}PC_{i(1,2,...,5)} + \\beta_j PEER_{j}+ \\epsilon Incorporate all four datasets into a single model (multi-cohort model): Eresid=βGXG+βdatasetXdataset+ϵ E_{resid} = \\beta_G X_G + \\beta_{dataset} X_{dataset} + \\epsilon （三）Determine whether lead eQTLs are cell type dependent 为了验证lead eQTL是否为细胞类型特异，又引入了基因型和细胞类型的交叉效应与个体的随机效应进行线性回归 Eresid=βGXG+βcell_typeXcell_type+βG×cell_typeXG×cell_type+(ϕ∣donor)+ϵ E_{resid} = \\beta_G X_G + \\beta_{cell\\_type}X_{cell\\_type} + \\beta_{G\\times cell\\_type} X_{G\\times cell\\_type} + (\\phi | donor) + \\epsilon （四）3 rounds conditonal analysis 将lead eQTLs作为covar进行再次进行三轮拟合，筛选Secondary eQTLs（P-Value \u0026lt; 5e-8) （五）HLA genes exhibit cell-state-dependent expression 随后使用hPC方法鉴定不同的cell state（类似拟时分析） （六）Modeling dynamic eQTLs at single-cell resolution 非负二项分布混合线性模型 利用each gene的UMI counts作为因变量进行回归分析 对hPC得到的不同cell state进行单细胞层次的eQTL mapping ","permalink":"https://antidington.github.io/posts/hla-single-cell-regulation/","summary":"\u003ch2 id=\"一单细胞数据集\"\u003e（一）单细胞数据集\u003c/h2\u003e\n\u003cul\u003e\n\u003cli\u003e69个滑膜样本\u003c/li\u003e\n\u003cli\u003e22个肠样本\u003c/li\u003e\n\u003cli\u003e91个PBMC体外培养样本\u003c/li\u003e\n\u003cli\u003eOneK1K cohort\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cimg loading=\"lazy\" src=\"/posts/hla-single-cell-regulation/images/17027072677260.jpg\"\u003e\u003c/p\u003e\n\u003ch2 id=\"二pseudobulk-cell-type-specific-eqtl\"\u003e（二）Pseudobulk cell type specific eQTL\u003c/h2\u003e\n\u003cul\u003e\n\u003cli\u003e由于作者关注HLA基因，所以只对相关的髓系细胞、T细胞、B细胞进行了分析\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cimg loading=\"lazy\" src=\"/posts/hla-single-cell-regulation/images/17027078386181.jpg\"\u003e\u003c/p\u003e","title":"Mapping the dynamic genetic regulatory architecture of HLA genes at single-cell resolution"},{"content":"Hi there! 👋🏻\nI’m a PhD student at Beijing Institute of Genomics, Chinese Academy of Science.\nI’m interested in population genetics and single cell genetics, I’m working on integrate both of them to explore the mechanism of diseases including coronary artery diseases.\nYou can reach me through the following email: wenjichen@big.ac.cn\n","permalink":"https://antidington.github.io/about/","summary":"\u003cp\u003eHi there! 👋🏻\u003cbr\u003e\nI’m a PhD student at Beijing Institute of Genomics, Chinese Academy of Science.\u003cbr\u003e\nI’m interested in population genetics and single cell genetics, I’m working on integrate both of them to explore the mechanism of diseases including coronary artery diseases.\u003cbr\u003e\nYou can reach me through the following email: \u003ca href=\"mailto:wenjichen@big.ac.cn\"\u003ewenjichen@big.ac.cn\u003c/a\u003e\u003c/p\u003e","title":"About"}]