Potential core genes associated with COVID-19 identified via weighted gene co-expression network analysis

Abstract

Aims: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel virus belonging to the Coronaviridae family that causes coronavirus disease (COVID-19). This disease rapidly reached pandemic status, presenting a serious threat to global health. However, the detailed molecular mechanism contributing to COVID-19 has not yet been elucidated.

Methods: The expression profiles, including the mRNA levels, of samples from patients infected with SARS-CoV-2 along with clinical data were obtained from the GSE152075 dataset in the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis (WGCNA) was used to identify co-expression modules, which were then implemented to evaluate the relationships between fundamental modules and clinical traits. The differentially expressed genes (DEGs), gene ontology (GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were evaluated using R software packages.

Results: A total of 377 SARS-CoV-2-infected samples and 54 normal samples with available clinical and genetic data were obtained from the GEO database. There were 1444 DEGs identified between the sample types, which were used to screen out 11 co-expression modules in the WGCNA. Six co-expression modules were significantly associated with three clinical traits (SARS-CoV-2 positivity, age, and sex). Among the DEGs in two modules significantly correlated with SARS-CoV-2 positivity, enrichment was observed in the biological process of viral infection strategies (viral translation) in the GO analysis. The KEGG signalling pathway analysis demonstrated that the DEGs in the two modules were commonly enriched in oxidative phosphorylation, ribosome, and thermogenesis pathways. Moreover, a five-core gene set (RPL35A, RPL7A, RPS15, RPS20, and RPL17) with top connectivity with other genes was identified in the SARS-CoV-2 infection modules, suggesting that these genes may be indispensable in viral transcription after infection.

Conclusion: The identified core genes and signalling pathways associated with SARS-CoV-2 infection can significantly supplement the current understanding of COVID-19. The five core genes encoding ribosomal proteins may be indispensable in viral protein biosynthesis after SARS-CoV-2 infection and serve as therapeutic targets for COVID-19 treatment. These findings can be used as a basis for creating a hypothetical model for future experimental studies regarding associations of SARS-CoV-2 infection with ribosomal protein function.