Aishwarya S, Gunasekaran K
Department of Bioinformatics, Stella Maris College (Autonomous), Chennai, India.
CAS in Crystallography and Biophysics, University of Madras, Chennai, India.
Biochem Genet. 2024 Feb;62(1):311-332. doi: 10.1007/s10528-023-10414-9. Epub 2023 Jun 19.
Gastrointestinal manifestations in COVID-19 were attributed to 74-86% of the hospitalised patients due to severe or prolonged pathogenesis. Though it is a respiratory disease, the impact it elicits on the gastrointestinal tract and brain are intense. Inflammatory bowel disease including Crohn's disease and ulcerative colitis are idiopathic inflammatory disorders of the gastrointestinal tract. The intrinsic mechanisms involved in gut inflammations due to a respiratory viral disease can be deciphered when the gene expression profiles of COVID-19 and IBD are compared. The current study utilises an integrated bioinformatics approach to unravel them. The publicly available gene expression profiles of colon transcriptomes infected with COVID-19, Crohn's disease and Ulcerative colitis were retrieved, integrated and analysed for the identification of differentially expressed genes. The inter-relational analysis along with gene annotation and pathway enrichment detailed the functional and metabolic pathways of the genes during normal and diseased conditions. The protein-protein interactions deduced from the STRING database and the identified hub genes predicted potential biomarker candidates for COVID-19, Crohn's disease and ulcerative colitis. The inflammatory response pathways were upregulated and enrichment of chemokine signalling, altered lipid metabolism, coagulation and complement cascades were seen in all three conditions along with impaired transport mechanisms. CXCL11, MMP10, and CFB are predicted to be overexpressed biomarkers, whilst GUCA2A, SLC13A2, CEACAM, and IGSF9 as downregulated novel biomarker candidates for colon inflammations. The three miRNAs hsa-miR-16-5p, hsa-miR-21-5p, and hsa-miR-27b-5p exhibited significant interactions with the upregulated hub genes and four long non-coding RNAs NEAT1, KCNQ1OT1, and LINC00852 capable of regulating miRNA were also predicted. This study offers significant information on the underlying molecular mechanisms of inflammatory bowel disease with identification of potential biomarkers.
由于严重或长期的发病机制，74%至86%的新冠住院患者出现了胃肠道表现。尽管它是一种呼吸系统疾病，但其对胃肠道和大脑的影响却很强烈。炎症性肠病，包括克罗恩病和溃疡性结肠炎，是胃肠道的特发性炎症性疾病。当比较新冠和炎症性肠病的基因表达谱时，可以解读由呼吸道病毒疾病引起的肠道炎症所涉及的内在机制。本研究采用综合生物信息学方法来揭示这些机制。检索、整合并分析了公开可用的新冠、克罗恩病和溃疡性结肠炎感染的结肠转录组基因表达谱，以鉴定差异表达基因。关联分析以及基因注释和通路富集详细阐述了正常和患病状态下基因的功能和代谢通路。从STRING数据库推导的蛋白质-蛋白质相互作用以及鉴定出的枢纽基因预测了新冠、克罗恩病和溃疡性结肠炎潜在的生物标志物候选物。在所有三种情况下，炎症反应通路均上调，趋化因子信号传导富集、脂质代谢改变、凝血和补体级联反应出现，同时转运机制受损。CXCL11、MMP10和CFB被预测为过表达的生物标志物，而GUCA2A、SLC13A2、CEACAM和IGSF9作为结肠炎症下调的新型生物标志物候选物。三种微小RNA（hsa-miR-16-5p、hsa-miR-21-5p和hsa-miR-27b-5p）与上调的枢纽基因表现出显著相互作用，还预测了四种能够调节微小RNA的长链非编码RNA（NEAT1、KCNQ1OT1和LINC00852）。本研究通过鉴定潜在生物标志物，提供了关于炎症性肠病潜在分子机制的重要信息。
