Abstract
The coronavirus disease-2019 (COVID-19) pandemic has caused an enormous loss of lives. Various clinical trials of vaccines and drugs are being conducted worldwide; nevertheless, as of today, no effective drug exists for COVID-19. The identification of key genes and pathways in this disease may lead to finding potential drug targets and biomarkers. Here, we applied weighted gene co-expression network analysis and LIME as an explainable artificial intelligence algorithm to comprehensively characterize transcriptional changes in bronchial epithelium cells (primary human lung epithelium (NHBE) and transformed lung alveolar (A549) cells) during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our study detected a network that significantly correlated to the pathogenicity of COVID-19 infection based on identified hub genes in each cell line separately. The novel hub gene signature that was detected in our study, including PGLYRP4 and HEPHL1, may shed light on the pathogenesis of COVID-19, holding promise for future prognostic and therapeutic approaches. The enrichment analysis of hub genes showed that the most relevant biological process and KEGG pathways were the type I interferon signaling pathway, IL-17 signaling pathway, cytokine-mediated signaling pathway, and defense response to virus categories, all of which play significant roles in restricting viral infection. Moreover, according to the drug–target network, we identified 17 novel FDA-approved candidate drugs, which could potentially be used to treat COVID-19 patients through the regulation of four hub genes of the co-expression network. In conclusion, the aforementioned hub genes might play potential roles in translational medicine and might become promising therapeutic targets. Further in vitro and in vivo experimental studies are needed to evaluate the role of these hub genes in COVID-19.
Highlights
Since December 2019, millions of people have been directly or indirectly affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) global pandemic
Based on Differentially expressed genes (DEGs) analysis between SARS-CoV-2-treated and mock-treated cell lines, there were a total of 20 genes in A549 cells and 42 genes in NHBE cells (34 up-regulated, eight down-regulated) (Figure S2)
Using expression data from human lung epithelial cells, including independent biological triplicates of primary human lung epithelium (NHBE) and transformed lung alveolar (A549) cells, we performed deeper transcriptomic analysis to better understand the molecular basis of COVID-19 and identify putative markers
Summary
Since December 2019, millions of people have been directly or indirectly affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) global pandemic. Some patients develop severe illnesses, including pneumonia, acute respiratory distress syndrome, pulmonary edema, acute kidney injury, or quick multiple organ failure [2,3,4,5]. The involvement of the lungs suggests viral dissemination after the initial infection. Viral RNA has been identified in symptomatic patients in the upper airways, with greater viral loads in nasal swabs than those collected from the throat [8]. Comparable viral loads have been observed in an asymptomatic patient, suggesting that the nasal epithelium is a significant portal for initial infection and may act as the main reservoir for viral dissemination across the respiratory mucosa, an essential viral transmission mediating locus. To improve diagnostic and therapeutic approaches, it is critical to recognize the cells and mechanisms that host viruses and enable viral replication, and what contributes to the inflammation and pathogenesis of the disease
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