Chanchal Shankar, Sharma Swati, Mohd Syed, Sultan Armiya, Mishra Aastha, Ashraf Mohammad Zahid
Department of Biotechnology, Faculty of Natural Sciences, Jamia Millia Islamia, Delhi, India.
Cardio Respiratory Disease unit, CSIR- Institute of Genomics and Integrative Biology, Delhi, India.
TH Open. 2024 Feb 2;8(1):e81-e92. doi: 10.1055/a-2222-9126. eCollection 2024 Jan.
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.
炎症和血栓形成是两个不同但相互依存的生理过程。炎症会导致凝血系统激活，进而引导免疫系统及其激活，引发血栓形成的病理生理学过程，这一过程被称为免疫血栓形成。然而，与免疫系统和凝血相关的潜在分子机制尚未得到广泛研究。受此启发，我们利用包括静脉血栓形成、系统性红斑狼疮、类风湿性关节炎和炎症性肠病在内的四种疾病的公开可用数据集进行了全面的基因表达荟萃分析。基于综合效应量方法，共鉴定出所有四个数据集共有的609个差异表达基因（DEG）。对这些DEG进行的通路富集分析显示，各种表观遗传通路如组蛋白修饰酶、蛋白质翻译后修饰、染色质组织、染色质修饰酶、组蛋白乙酰转移酶（HATs）使蛋白质乙酰化等均有富集。基于网络的蛋白质-蛋白质相互作用分析表明，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个枢纽基因的miRNA相互作用伙伴。表观转录组学调控的主导地位为对相同四种疾病的miRNA数据集进行荟萃分析奠定了基础。我们鉴定出这些疾病共有的30个差异表达微小RNA（DEmiR）。从10个顶级枢纽基因的miRNA相互作用伙伴列表中选出9个共同的DEmiR，它们与从微小RNA数据集中获取的显著DEmiR相同。这些共同的DEmiR被发现可调控参与表观遗传调控的基因，这表明在免疫血栓形成和炎症性疾病的背景下，一个有前景的表观遗传方面有待未来的分子研究去探索。
