Identification of key regulatory genes in the pathogenesis of COVID-19 and sepsis: An observational study

Abstract

Patients with severe COVID-19 and those with sepsis have similar clinical manifestations. We used bioinformatics methods to identify the common hub genes in these 2 diseases. Two RNA-seq datasets from the Gene Expression Omnibus were used to identify common differentially expressed genes (DEGs) in COVID-19 and sepsis. These common genes were used for analysis of functional enrichment; pathway analysis; identification of associated transcription factors, metabolites, and miRNAs; and mapping of protein–protein interaction networks. The major hub genes of COVID-19 and sepsis were identified, and validation datasets were used to assess the value of these hub genes using receiver operating characteristic (ROC) curves. Analysis of the 800 common DEGs for COVID-19 and sepsis, as well as common transcription factors, miRNAs, and metabolites, demonstrated that the immune response had a key role in both diseases. DLGAP5, BUB1, CDK1, CCNB1, and BUB1B were the most important common hub genes. Analysis of a validation cohort indicated these 5 genes had significantly higher expression in COVID-19 patients and sepsis patients than in corresponding controls, and the area under the ROC curves ranged from 0.832 to 0.981 for COVID-19 and 0.840 to 0.930 for sepsis. We used bioinformatics tools to identify common DEGs, miRNAs, and transcription factors for COVID-19 and sepsis. The 5 identified hub genes had higher expression in validation cohorts of COVID-19 and sepsis. These genes had good or excellent diagnostic performance based on ROC analysis, and therefore have potential use as novel markers or therapeutic targets.