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Updated: Oct 22, 2025
High-Throughput Transcriptome Analysis for Investigating Host-Pathogen Interactions
Published on: March 5, 2022
Weighted Gene Co-Expression Network Analysis Combined with Machine Learning Validation to Identify Key Modules and
Hassan Karami1, Afshin Derakhshani2,3, Mohammad Ghasemigol4
1Student Research Committee, Birjand University of Medical Sciences, Birjand 9717853577, Iran.
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.
Insights
Researchers identified novel hub genes, PGLYRP4 and HEPHL1, and 17 FDA-approved drugs for treating COVID-19. These findings offer potential therapeutic targets and prognostic biomarkers for coronavirus disease-2019.
Area of Science:
- Genomics and Bioinformatics
- Computational Biology
- Infectious Disease Research
Background:
- The COVID-19 pandemic caused significant mortality, with no definitive antiviral drug available.
- Identifying key genes and pathways is crucial for developing effective treatments and biomarkers for COVID-19.
- Understanding transcriptional changes in lung cells during SARS-CoV-2 infection is vital for elucidating disease mechanisms.
Purpose of the Study:
- To characterize transcriptional changes in bronchial epithelium cells during SARS-CoV-2 infection using advanced computational methods.
- To identify key genes and pathways associated with COVID-19 pathogenicity.
- To discover potential therapeutic targets and FDA-approved drugs for COVID-19 treatment.
Main Methods:
- Weighted gene co-expression network analysis (WGCNA) to identify gene networks correlated with COVID-19.
- Explainable artificial intelligence (LIME) to analyze transcriptional data from NHPE and A549 lung cell lines.
- Enrichment analysis to determine biological processes and KEGG pathways associated with identified hub genes.
- Drug-target network analysis to identify potential therapeutic candidates.
Main Results:
- A significant gene network correlated with COVID-19 pathogenicity was detected in both NHPE and A549 cells.
- Novel hub genes, including PGLYRP4 and HEPHL1, were identified as potential key players in COVID-19 pathogenesis.
- Enrichment analysis highlighted the involvement of type I interferon, IL-17 signaling, and cytokine-mediated pathways in viral response.
- Seventeen FDA-approved drugs were identified as potential candidates for COVID-19 treatment by targeting identified hub genes.
Conclusions:
- The identified hub genes (PGLYRP4, HEPHL1) show promise as prognostic and therapeutic targets for COVID-19.
- The study provides a foundation for translational medicine approaches to combat COVID-19.
- Further in vitro and in vivo studies are warranted to validate the role of these hub genes and candidate drugs in COVID-19 treatment.
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