Center for Genetic Epidemiology & Genomics, Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, Jiangsu 215123, PR China.
Jiangsu Key Laboratory of Preventive & Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, Jiangsu 215123, PR China.
Epigenomics. 2019 Nov;11(14):1601-1612. doi: 10.2217/epi-2019-0028. Epub 2019 Nov 6.
To identify epigenetically regulated network of genes in peripheral blood mononuclear cells significant for rheumatoid arthritis (RA). Differentially expressed genes (DEGs) and their associated differentially expressed miRNAs and differentially methylated positions (DMPs) were identified. Causal inference test (CIT) identified the causal regulation chains. The analyses, for example, weighted gene co-expression network (WGCNA), protein-protein interaction and functional enrichment, evaluated interaction patterns among the DEGs and the associated epigenetic factors. A total of 181 DEGs were identified. The DEGs were significantly regulated by DMPs and/or differentially expressed miRNAs. Causal inference test analyses identified 18 causal chains of DMP-DEG-RA and 16 intermediate DEGs enriched in 'protein kinase inhibitor activity'. was co-expressed with other 9 intermediate genes and 11 known RA-associated genes and played a pivotal role in the co-expression network. Epigenetically regulated network of genes in peripheral blood mononuclear cells (PBMC) contributed to RA. The causal DMPs and key intermediate genes may serve as potential biomarkers for RA.
旨在鉴定与类风湿关节炎（RA）相关的外周血单个核细胞中受表观遗传调控的基因网络。鉴定差异表达基因（DEGs）及其相关的差异表达miRNA 和差异甲基化位置（DMPs）。因果推断测试（CIT）确定了因果调节链。例如，加权基因共表达网络（WGCNA）、蛋白质-蛋白质相互作用和功能富集分析评估了 DEGs 与相关表观遗传因子之间的相互作用模式。鉴定出 181 个差异表达基因。DEGs 受到 DMP 和/或差异表达 miRNA 的显著调控。因果推断测试分析鉴定出 18 条 DMP-DEG-RA 的因果链和 16 个富含“蛋白激酶抑制剂活性”的中间 DEGs。与其他 9 个中间基因和 11 个已知的 RA 相关基因共表达，在共表达网络中起着关键作用。外周血单个核细胞（PBMC）中基因的表观遗传调控网络与 RA 有关。因果 DMPs 和关键中间基因可能作为 RA 的潜在生物标志物。
