A network-based systems biology approach for identification of shared Gene signatures between male and female in COVID-19 datasets

Abstract

The novel coronavirus (SARS-CoV-2) has expanded rapidly worldwide. Now it has covered more than 150 countries worldwide. It is referred to as COVID-19. SARS-CoV-2 mainly affects the respiratory systems of humans that can lead up to serious illness or even death in the presence of different comorbidities. However, most COVID-19 infected people show mild to moderate symptoms, and no medication is suggested. Still, drugs of other diseases have been used to treat COVID-19. Nevertheless, the absence of vaccines and proper drugs against the COVID-19 virus has increased the mortality rate. Albeit sex is a risk factor for COVID-19, none of the studies considered this risk factor for identifying biomarkers from the RNASeq count dataset. Men are more likely to undertake severe symptoms with different comorbidities and show greater mortality compared with women. From this standpoint, we aim to identify shared gene signatures between males and females from the human COVID-19 RNAseq count dataset of peripheral blood cells using a robust voom approach. We identified 1341 overlapping DEGs between male and female datasets. The gene ontology (GO) annotation and pathway enrichment analysis revealed that DEGs are involved in various BP categories such as nucleosome assembly, DNA conformation change, DNA packaging, and different KEGG pathways such as cell cycle, ECM-receptor interaction, progesterone-mediated oocyte maturation, etc. Ten hub-proteins (UBC, KIAA0101, APP, CDK1, SUMO2, SP1, FN1, CDK2, E2F1, and TP53) were unveiled using PPI network analysis. The top three miRNAs (mir-17–5p, mir-20a-5p, mir-93–5p) and TFs (PPARG, E2F1 and KLF5) were uncovered. In conclusion, the top ten significant drugs (roscovitine, curcumin, simvastatin, fulvestrant, troglitazone, alvocidib, L-alanine, tamoxifen, serine, and doxorubicin) were retrieved using drug repurposing analysis of overlapping DEGs, which might be therapeutic agents of COVID-19.