PDF(Pubmed)
Abstract：
Inflammation and thrombosis are two distinct yet interdependent physiological processes. The inflammation results in the activation of the coagulation system that directs the immune system and its activation, resulting in the initiation of the pathophysiology of thrombosis, a process termed immune-thrombosis. Still, the shared underlying molecular mechanism related to the immune system and coagulation has not yet been explored extensively. Inspired to answer this, we carried out a comprehensive gene expression meta-analysis using publicly available datasets of four diseases, including venous thrombosis, systemic lupus erythematosus, rheumatoid arthritis, and inflammatory bowel disease. A total of 609 differentially expressed genes (DEGs) shared by all four datasets were identified based on the combined effect size approach. The pathway enrichment analysis of the DEGs showed enrichment of various epigenetic pathways such as histone-modifying enzymes, posttranslational protein modification, chromatin organization, chromatin-modifying enzymes, HATs acetylate proteins. Network-based protein-protein interaction analysis showed epigenetic enzyme coding genes dominating among the top hub genes. The miRNA-interacting partner of the top 10 hub genes was determined. The predomination of epitranscriptomics regulation opens a layout for the meta-analysis of miRNA datasets of the same four diseases. We identified 30 DEmiRs shared by these diseases. There were 9 common DEmiRs selected from the list of miRNA-interacting partners of top 10 hub genes and shared significant DEmiRs from microRNAs dataset acquisition. These common DEmiRs were found to regulate genes involved in epigenetic modulation and indicate a promising epigenetic aspect that needs to be explored for future molecular studies in the context of immunothrombosis and inflammatory disease.
摘要：
炎症和血栓形成是两个不同但相互依赖的生理过程。炎症导致指导免疫系统的凝血系统的激活及其激活，导致血栓形成的病理生理学的开始，一个被称为免疫血栓形成的过程。尽管如此，与免疫系统和凝血相关的共同的潜在分子机制尚未得到广泛探索。启发回答这个问题，我们使用四种疾病的公开数据集进行了全面的基因表达荟萃分析，包括静脉血栓形成,系统性红斑狼疮,类风湿性关节炎,和炎症性肠病.基于组合效应大小方法鉴定了所有四个数据集共有的总共609个差异表达基因(DEGs)。DEGs的途径富集分析显示了各种表观遗传途径的富集，如组蛋白修饰酶，翻译后蛋白质修饰，染色质组织，染色质修饰酶，HAT乙酰化蛋白。基于网络的蛋白质-蛋白质相互作用分析显示，表观遗传酶编码基因在顶级枢纽基因中占主导地位。确定了前10个hub基因的miRNA相互作用伴侣。表观组学调控的主导为相同四种疾病的miRNA数据集的荟萃分析打开了布局。我们确定了这些疾病共有的30个DEmiR。从前10个hub基因的miRNA相互作用伴侣列表中选择了9个常见的DEmiR，并且从microRNA数据集获取中共享了重要的DEmiR。发现这些常见的DEmiR调节与表观遗传调节有关的基因，并表明有希望的表观遗传方面，需要在免疫血栓形成和炎性疾病的背景下进行未来的分子研究。
