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. 2020 Oct;10(10):422.
doi: 10.1007/s13205-020-02406-y. Epub 2020 Sep 11.

Identification of potential mRNA panels for severe acute respiratory syndrome coronavirus 2 (COVID-19) diagnosis and treatment using microarray dataset and bioinformatics methods

Basavaraj Vastrad  1 , Chanabasayya Vastrad  2 , Anandkumar Tengli  3
Affiliations

Identification of potential mRNA panels for severe acute respiratory syndrome coronavirus 2 (COVID-19) diagnosis and treatment using microarray dataset and bioinformatics methods

Basavaraj Vastrad et al. 3 Biotech. 2020 Oct.

Abstract

The goal of the present investigation is to identify the differentially expressed genes (DEGs) between SARS-CoV-2 infected and normal control samples to investigate the molecular mechanisms of infection with SARS-CoV-2. The microarray data of the dataset E-MTAB-8871 were retrieved from the ArrayExpress database. Pathway and Gene Ontology (GO) enrichment study, protein-protein interaction (PPI) network, modules, target gene-miRNA regulatory network, and target gene-TF regulatory network have been performed. Subsequently, the key genes were validated using an analysis of the receiver operating characteristic (ROC) curve. In SARS-CoV-2 infection, a total of 324 DEGs (76 up- and 248 down-regulated genes) were identified and enriched in a number of associated SARS-CoV-2 infection pathways and GO terms. Hub and target genes such as TP53, HRAS, MAPK11, RELA, IKZF3, IFNAR2, SKI, TNFRSF13C, JAK1, TRAF6, KLRF2, CD1A were identified from PPI network, target gene-miRNA regulatory network, and target gene-TF regulatory network. Study of the ROC showed that ten genes (CCL5, IFNAR2, JAK2, MX1, STAT1, BID, CD55, CD80, HAL-B, and HLA-DMA) were substantially involved in SARS-CoV-2 patients. The present investigation identified key genes and pathways that deepen our understanding of the molecular mechanisms of SARS-CoV-2 infection, and could be used for SARS-CoV-2 infection as diagnostic and therapeutic biomarkers.

Keywords: Bioinformatics analysis; Biomarkers; Differentially expressed genes; Protein–protein interaction (PPI) network; SARS-CoV-2 infection.

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Conflict of interest statement

Conflict of interestThe authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
The workflow representing the methodology and the major outcome of the study. SARS-CoV-2—Severe acute respiratory syndrome coronavirus 2 infection - breast cancer, GO—gene ontology, miRNA—MicroRNA, TF-transcription factor, DEGs—deferential expressed genes
Fig. 2
Fig. 2
Box plots of the normalized data. a 22 SARS-CoV-2 infected samples b 10 normal control samples. Horizontal axis represents the sample symbol and the vertical axis represents the gene expression values. The black line in the box plot represents the median value of gene expression
Fig. 3
Fig. 3
Volcano plot of differentially expressed genes. Genes with a significant change of more than twofold were selected. Green dot on right side ( formula image ) represented up regulated significant genes and red dot on left side (formula image ) represented down regulated significant genes
Fig. 4
Fig. 4
Heat map of up regulated differentially expressed genes. Legend on the top left indicate log fold change of genes. White represents decreased expression of genes; light green represents not significant expression of genes; dark green represents increased expression of genes. (A1–A10 = Normal control samples; B1–B22 = SARS-CoV-2 infected samples)
Fig. 5
Fig. 5
Heat map of down regulated differentially expressed genes. Legend on the top left indicate log fold change of genes. White represents decreased expression of genes; light pink represents not significant expression of genes; dark pink represents increased expression of genes. (A1–A10 = Normal control samples; B1–B22 = SARS-CoV-2 infected samples)
Fig. 6
Fig. 6
Protein–protein interaction network of up regulated genes. Green nodes (formula image ) denotes up regulated genes; Blue lines (formula image ) denotes edges (Interactions)
Fig. 7
Fig. 7
Scatter plot for up regulated genes. (A—Node degree; B—Betweenness centrality; C—Stress centrality; D—Closeness centrality; E—Clustering coefficient)
Fig. 8
Fig. 8
Protein–protein interaction network of down regulated genes. Red nodes (formula image ) denotes down regulated genes; Pink lines (formula image ) denotes edges (Interactions)
Fig. 9
Fig. 9
Scatter plot for down regulated genes. (A—Node degree; B—Betweenness centrality; C—Stress centrality; D—Closeness centrality; E—Clustering coefficient)
Fig. 10
Fig. 10
Modules in PPI network. The green nodes denote the up regulated genes. Green nodes (formula image ) denotes up regulated genes; Blue lines (formula image ) denotes edges (Interactions)
Fig. 11
Fig. 11
Modules in PPI network. The red nodes denote the down regulated genes. Red nodes (formula image ) denotes down regulated genes; Pink lines (formula image ) denotes edges (Interactions)
Fig. 12
Fig. 12
The network of up regulated genes and their related miRNAs. The green circles nodes (formula image ) are the up regulated genes; yellow diamond nodes (formula image ) are the miRNAs; Pink lines (formula image ) denotes edges (Interactions)
Fig. 13
Fig. 13
The network of down regulated genes and their related miRNAs. The red circles nodes (formula image ) are the down regulated genes; blue diamond nodes (formula image ) are the miRNAs; Sku blue lines (formula image ) denotes edges (Interactions)
Fig. 14
Fig. 14
The network of up regulated genes and their related TFs. The green circles nodes (formula image ) are the up regulated genes; Blue triangle nodes (formula image ) are the TFs; Purple line (formula image ) denotes edges (Interactions)
Fig. 15
Fig. 15
The network of down regulated genes and their related TFs. The Red circles nodes (formula image ) are the down regulated genes; Blue triangle nodes (formula image ) are the TFs; Yelow line (formula image ) denotes edges (Interactions)
Fig. 16
Fig. 16
ROC curve validated the sensitivity, specificity of hub genes as a predictive biomarker for SARS-CoV-2 diagnosis. a CCL5 b IFNAR2 c JAK2 d MX1 e STAT1 f BID g CD55 h CD80 i HAL-B j HLA-DMA
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References

    1. Alaoui L, Palomino G, Zurawski S, Zurawski G, Coindre S, Dereuddre-Bosquet N, Lecuroux C, Goujard C, Vaslin B, Bourgeois C, et al. Early SIV and HIV infection promotes the LILRB2/MHC-I inhibitory axis in cDCs. Cell Mol Life Sci. 2018;75(10):1871–1887. doi: 10.1007/s00018-017-2712-9. - DOI - PMC - PubMed
    1. Alturaiki W, McFarlane AJ, Rose K, Corkhill R, McNamara PS, Schwarze J, Flanagan BF. Expression of the B cell differentiation factor BAFF and chemokine CXCL13 in a murine model of respiratory syncytial virus infection. Cytokine. 2018;110:267–271. doi: 10.1016/j.cyto.2018.01.014. - DOI - PubMed
    1. Amet T, Ghabril M, Chalasani N, Byrd D, Hu N, Grantham A, Liu Z, Qin X, He JJ, Yu Q. CD59 incorporation protects hepatitis C virus against complement-mediated destruction. Hepatology. 2012;55(2):354–363. doi: 10.1002/hep.24686. - DOI - PMC - PubMed
    1. Anderson SL, Carton JM, Lou J, Xing L, Rubin BY. Interferon-induced guanylate binding protein-1 (GBP-1) mediates an antiviral effect against vesicular stomatitis virus and encephalomyocarditis virus. Virology. 1999;256(1):8–14. doi: 10.1006/viro.1999.9614. - DOI - PubMed
    1. Antunes KH, Becker A, Franceschina C, de Freitas DD, Lape I, da Cunha MD, Leitão L, Rigo MM, Pinto LA, Stein RT, et al. Respiratory syncytial virus reduces STAT3 phosphorylation in human memory CD8 T cells stimulated with IL-21. Sci Rep. 2019;9(1):17766. doi: 10.1038/s41598-019-54240-9. - DOI - PMC - PubMed