Bioinformatics analyses of significant genes, related pathways, and candidate diagnostic biomarkers and molecular targets in SARS-CoV-2/COVID-19

Gene Rep. 2020 Dec;21:100956. doi: 10.1016/j.genrep.2020.100956. Epub 2020 Nov 4.


Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) infection is a leading cause of pneumonia and death. The aim of this investigation is to identify the key genes in SARS-CoV-2 infection and uncover their potential functions. We downloaded the expression profiling by high throughput sequencing of GSE152075 from the Gene Expression Omnibus database. Normalization of the data from primary SARS-CoV-2 infected samples and negative control samples in the database was conducted using R software. Then, joint analysis of the data was performed. Pathway and Gene ontology (GO) enrichment analyses were performed, and the protein-protein interaction (PPI) network, target gene - miRNA regulatory network, target gene - TF regulatory network of the differentially expressed genes (DEGs) were constructed using Cytoscape software. Identification of diagnostic biomarkers was conducted using receiver operating characteristic (ROC) curve analysis. 994 DEGs (496 up regulated and 498 down regulated genes) were identified. Pathway and GO enrichment analysis showed up and down regulated genes mainly enriched in the NOD-like receptor signaling pathway, Ribosome, response to external biotic stimulus and viral transcription in SARS-CoV-2 infection. Down and up regulated genes were selected to establish the PPI network, modules, target gene - miRNA regulatory network, target gene - TF regulatory network revealed that these genes were involved in adaptive immune system, fluid shear stress and atherosclerosis, influenza A and protein processing in endoplasmic reticulum. In total, ten genes (CBL, ISG15, NEDD4, PML, REL, CTNNB1, ERBB2, JUN, RPS8 and STUB1) were identified as good diagnostic biomarkers. In conclusion, the identified DEGs, hub genes and target genes contribute to the understanding of the molecular mechanisms underlying the advancement of SARS-CoV-2 infection and they may be used as diagnostic and molecular targets for the treatment of patients with SARS-CoV-2 infection in the future.

Keywords: Bioinformatics; CBL, Cbl proto-oncogene; DEGs, differentially expressed genes; Diagnosis; GO, Gene ontology; ISG15, ISG15 ubiquitin like modifier; Key genes; NEDD4, NEDD4 E3 ubiquitin protein ligase; PML, promyelocyticleukemia; PPI, protein-protein interaction; Pathways; REL, REL proto-oncogene, NF-kB subunit; ROC, receiver operating characteristic; SARS-CoV-2 infection; SARS-CoV-2, Severe acute respiratory syndrome corona virus 2.