Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 May 24;23(2):175.
doi: 10.1007/s10142-023-01091-3.

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

Zihao Liang  1 , Xudong Zheng  2 , Yuan Wang  1 , Kai Chu  3 , Yanan Gao  4
Affiliations

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

Zihao Liang et al. Funct Integr Genomics. .

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
A schematic overview of the study workflow
Fig. 2
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
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
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
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
Fig. 6
Hub gene-transcription factor regulatory interaction network. Blue circles indicate transcription factors, and red circles are hub genes
Fig. 7
Fig. 7
Hub gene-miRNA regulatory interaction network. Green triangle nodes indicate miRNAs, and red ovals are hub genes
Fig. 8
Fig. 8
Gene-disease association network. The yellow diamond node represents the disease, and the red circle node represents the gene
See this image and copyright information in PMC

References

    1. Abdel-Aziz MI, Kermani NZ, Neerincx AH, Vijverberg SJH, Guo Y, Howarth P, Dahlen SE, Djukanovic R, Sterk PJ, Kraneveld AD, Maitland-van der Zee AH, Chung KF, Adcock IM, On behalf the UBC Association of endopeptidases, involved in SARS-CoV-2 infection, with microbial aggravation in sputum of severe asthma. Allergy. 2021;76:1917–1921. doi: 10.1111/all.14731. - DOI - PubMed
    1. Arguni E, Supriyati E, Hakim MS, Daniwijaya EW, Makrufardi F, Rahayu A, Rovik A, Saraswati U, Oktoviani FN, Prastiwi N, Nuryastuti T, Wibawa T, Haryana SM. Co-infection of SARS-CoV-2 with other viral respiratory pathogens in Yogyakarta, Indonesia: a cross-sectional study. Ann Med Surg (Lond) 2022;77:103676. doi: 10.1016/j.amsu.2022.103676. - DOI - PMC - PubMed
    1. Bai L, Zhao Y, Dong J, Liang S, Guo M, Liu X, Wang X, Huang Z, Sun X, Zhang Z, Dong L, Liu Q, Zheng Y, Niu D, Xiang M, Song K, Ye J, Zheng W, Tang Z, Tang M, Zhou Y, Shen C, Dai M, Zhou L, Chen Y, Yan H, Lan K, Xu K. Coinfection with influenza A virus enhances SARS-CoV-2 infectivity. Cell Res. 2021;31:395–403. doi: 10.1038/s41422-021-00473-1. - DOI - PMC - PubMed
    1. Baker JR, Fenwick PS, Koss CK, Owles HB, Elkin SL, Fine J, Thomas M, El Kasmi KC, Barnes PJ, Donnelly LE (2022) IL-36 receptor agonist and antagonist imbalance drives neutrophilic inflammation in COPD. JCI Insight 7. 10.1172/jci.insight.155581 - PMC - PubMed
    1. Bankar R, Suvarna K, Ghantasala S, Banerjee A, Biswas D, Choudhury M, Palanivel V, Salkar A, Verma A, Singh A, Mukherjee A, Pai MGJ, Roy J, Srivastava A, Badaya A, Agrawal S, Shrivastav O, Shastri J, Srivastava S. Proteomic investigation reveals dominant alterations of neutrophil degranulation and mRNA translation pathways in patients with COVID-19. iScience. 2021;24:102135. doi: 10.1016/j.isci.2021.102135. - DOI - PMC - PubMed

LinkOut - more resources