Using system biology and bioinformatics to identify the influences of COVID-19 co-infection with influenza virus on COPD

Abstract

Coronavirus disease 2019 (COVID-19) has speedily increased mortality globally. Although they are risk factors for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), less is known about the common molecular mechanisms behind COVID-19, influenza virus A (IAV), and chronic obstructive pulmonary disease (COPD). This research used bioinformatics and systems biology to find possible medications for treating COVID-19, IAV, and COPD via identifying differentially expressed genes (DEGs) from gene expression datasets (GSE171110, GSE76925, GSE106986, and GSE185576). A total of 78 DEGs were subjected to functional enrichment, pathway analysis, protein-protein interaction (PPI) network construct, hub gene extraction, and other potentially relevant disorders. Then, DEGs were discovered in networks including transcription factor (TF)-gene connections, protein-drug interactions, and DEG-microRNA (miRNA) coregulatory networks by using NetworkAnalyst. The top 12 hub genes were MPO, MMP9, CD8A, HP, ELANE, CD5, CR2, PLA2G7, PIK3R1, SLAMF1, PEX3, and TNFRSF17. We found that 44 TFs-genes, as well as 118 miRNAs, are directly linked to hub genes. Additionally, we searched the Drug Signatures Database (DSigDB) and identified 10 drugs that could potentially treat COVID-19, IAV, and COPD. Therefore, we evaluated the top 12 hub genes that could be promising DEGs for targeted therapy for SARS-CoV-2 and identified several prospective medications that may benefit COPD patients with COVID-19 and IAV co-infection.

Keywords: COPD; COVID-19; Differentially expressed genes; Drug molecule; Hub genes; Influenza viruses.

Fig. 1

A schematic overview of the study workflow

Fig. 2

Visualization of the number of common differentially expressed genes (DEGs) among three diseases. A The volcano plot of differentially expressed genes in IAV datasets. B The volcano plot of differentially expressed genes in COVID-19 datasets. C The volcano plot of differentially expressed genes in COPD datasets. D Venn diagram showing the overlap of differentially expressed genes among COVID-19, IAV, and COPD

Fig. 3

GO analysis bubble diagram of the common DEGs among COVID-19, IAV, and COPD. A Biological processes. B Molecular function. C Cellular component

Fig. 4

Pathway enrichment analysis of the common DEGs among COVID-19, IAV, and COPD. A Reactome. (B) KEGG 2021. C BioPlanet. D WikiPathway 2021

Fig. 5

Protein-protein interaction (PPI) networks and hub genes for DEGs common to COVID-19, IAV, and COPD. A COVID-19, IAV, and COPD common DEGs in the PPI network. B The intersection of pivotal genes of different algorithms

Fig. 6

Hub gene-transcription factor regulatory interaction network. Blue circles indicate transcription factors, and red circles are hub genes

Fig. 7

Hub gene-miRNA regulatory interaction network. Green triangle nodes indicate miRNAs, and red ovals are hub genes

Fig. 8

Gene-disease association network. The yellow diamond node represents the disease, and the red circle node represents the gene