Functional Analysis of Monkeypox and Interrelationship between Monkeypox and COVID-19 by Bioinformatic Analysis

Abstract

The outbreak of monkeypox may be considered a novel and urgent threat after the coronavirus disease (COVID-19). No wide-ranging studies have been conducted on this disease since it was first reported. We systematically assessed the functional role of gene expression in cells infected with the monkeypox virus using transcriptome profiling and compared the functional relation with that of COVID-19. Based on the Gene Expression Omnibus database, we obtained 212 differentially expressed genes (DEGs) of GSE36854 and GSE21001 of monkeypox datasets. Enrichment analyses, including KEGG and gene ontology (GO) analyses, were performed to identify the common function of 212 DEGs of GSE36854 and GSE21001. CytoHubba and Molecular Complex Detection were performed to determine the core genes after a protein-protein interaction (PPI). Metascape/COVID-19 was used to compare DEGs of monkeypox and COVID-19. GO analysis of 212 DEGs of GSE36854 and GSE21001 for monkeypox infection showed cellular response to cytokine stimulus, cell activation, and cell differentiation regulation. KEGG analysis of 212 DEGs of GSE36854 and GSE21001 for monkeypox infection showed involvement of monkeypox in COVID-19, cytokine-cytokine receptor interaction, inflammatory bowel disease, atherosclerosis, TNF signaling, and T cell receptor signaling. By comparing our data with published transcriptome of severe acute respiratory syndrome coronavirus 2 infections in other cell lines, the common function of monkeypox and COVID-19 includes cytokine signaling in the immune system, TNF signaling, and MAPK cascade regulation. Thus, our data suggest that the molecular connections identified between COVID-19 and monkeypox elucidate the causes of monkeypox.

Figure 1

Flowchart of the present study. (a) Study design of the present study. DEG, differentially expressed genes; GO, gene ontology. (b) A Venn diagram between 212 DEGs of GSE21001 and GSE36854. 212 DEGs are shared across the GSE21001 and GSE36854 datasets. hpi, hour postinfection.

Figure 2

CytoHubba gene and MCODE enrichment analyses of monkeypox infection. (a) Analysis of the hub genes from 212 DEGs of monkeypox infection datasets (GSE21001 and GSE36854) from the PPI network with maximal clique centrality (MCC) algorithm in cytoHubba. Edges represent the protein-protein associations and display the protein-protein links. The red nodes show genes with a high MCC score. (b) The MCODE networks from 212 DEGs of monkeypox datasets of GSE21001 and GSE36854. The MCODE networks were analyzed using Metascape (https://metascape.org), which was accessed on May 11, 2022.

Figure 3

Gene ontology enrichment analysis and interaction of 212 DEGs between GSE36854 and GSE21001 of monkeypox infection. A network of GO BP terms (a) and KEGG pathway (b) of 212 DEGs of GSE36854 and GSE21001 of monkeypox infection by using the SHINEY GO 0.76 online tool (https://bioinformatics.sdstat.edu). (c) The top ten drugs related to monkeypox using 212 DEGs of GSE36854 and GSE21001 for MPXV infection by drug matador from the SHINEY GO 0.76 online tool.

Figure 4

DisGeNET, TRRUST, and PaGenBase of monkeypox infection. (a) DisGeNET database of 212 DEGs of GSE36854 and GSE21001 for enrichment analyses of diseases. (b) TRRUST database of 212 DEGs of GSE35854 and GSE21001 for enrichment of transcriptional regulators. (c) PaGenBase database for tissue characteristics of 212 DEGs of GSE36854 and GSE21001.

Figure 5

Comparison of biological function between monkeypox and COVID-19. (a) Hierarchical clustering of the enriched terms of 212 DEGs of GSE36854 and GSE21001 from monkeypox (my list) and as compared to COVID-19 cell lines analyzed through the metascape database. The metascape/COVID-19 database was accessed on May 11, 2022. (b) Network plot of enriched terms for DEGs of monkeypox infection compared to SARS-CoV-2 infection cell lines analyzed through the metascape database.

Figure 6

Comparison of the results of the DisGeNET and TRRUST analyses between monkeypox and SARS-CoV-2 infections. (a) DisGeNET database was used in the comparison between 212 DEGs of GSE36854 and GSE21001 from monkeypox infection (my list) and COVID-19 by Metascape/COVID-19 for enrichment analysis of diseases. (b) TRRUST database used for enrichment of transcriptional regulators; results of monkeypox and COVID-19 were compared using Metascape/COVID-19, which was accessed on May 11, 2022. My list means 212 DEGs from GSE36854 and GSE21001 for MPXV infection.