Bioinformatics approach to analyse COVID-19 biomarkers accountable for generation of intracranial aneurysm in COVID-19 patients

利用生物信息学方法分析导致新冠肺炎患者颅内动脉瘤发生的COVID-19生物标志物

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Abstract

COVID-19 became a health emergency on January 30, 2020. SARS-CoV-2 is the causative agent of the coronavirus disease known as COVID-19 and can develop cardiometabolic and neurological disorders. Intracranial aneurysm (IA) is considered the most significant reason for hemorrhagic stroke,and it accounts for approximately 85% of all subarachnoid hemorrhages (SAH). Retinoid signaling abnormalities may explain COVID-19's pathogenesis with inhibition of AEH2, from which COVID-19 infection may enhance aneurysm formation and rupture due to abrupt blood pressure changes, endothelial cell injury, and systemic inflammation. The objective of this study was to investigate the potential biomarkers, differentially expressed genes (DEGs), and metabolic pathways associated with both COVID-19 and intracranial aneurysm (IA) using simulation databases like DIsGeNET. The purpose was to confirm prior findings and gain a comprehensive understanding of the underlying mechanisms that contribute to the development of these conditions. We combined the regulated genes to describe intracranial aneurysm formation in COVID-19. To determine DEGs in COVID-19 and IA patient tissues, we compared gene expression transcriptomic datasets from healthy and diseased individuals. There were 41 differentially expressed genes (DEGs) shared by both the COVID-19 and IA datasets (27 up-regulated genes and 14 down-regulated genes). Using protein-protein interaction analysis, we were able to identify hub proteins (C3, NCR1, IL10RA, OXTR, RSAD2, CD38, IL10RB, MX1, IL10, GFAP, IFIT3, XAF1, USP18, OASL, IFI6, EPSTI1, CMPK2, and ISG15), which were not described as key proteins for both COVID-19 and IA before. We also used Gene Ontology analysis (6 significant ontologies were validated), Pathway analysis (the top 20 were validated), TF-Gene interaction analysis, Gene miRNA analysis, and Drug-Protein interaction analysis methods to comprehend the extensive connection between COVID-19 and IA. In Drug-Protein interaction analysis, we have gotten the following three drugs: LLL-3348, CRx139, and AV41 against IL10 which was both common for COVID-19 and IA disease. Our study with different cabalistic methods has showed the interaction between the proteins and pathways with drug analysis which may direct further treatment development for certain diseases.

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