Identification of Hub Genes and Key Pathways in TNF-α and IFN-γ Induced Cytokine Storms via Bioinformatics

Cytokine storms, an overaggressive immune response due to the overexpression of pro-inflammatory cytokines, have been identified to play a significant role in COVID-19 infections. Studies have shown that TNF-α and IFN-γ are integral to the process, however, its genetic mechanisms have yet to be fully elucidated. Herein, the key changes in the gene expression of TNF-α and IFN-γ induced cytokine storms are identified through differential gene analysis on the publicly available GEO GSE160163 dataset. GO and KEGG enrichment were used to annotate identified DEGs, and a PPI network was constructed based on the STRING database. A total of 446 differentially expressed genes were identified. Up-regulated genes and downregulated genes were enriched in viral immune response and infection pathways, and steroid biosynthesis and metabolic pathways, respectively. PPI construction revealed 1,834 interactions between 428 proteins, indicating their biological connectivity. Module analysis identified nine (9) hub genes: STAT1, CXCL10, CD274, CXCL9, IRF1, PSMB9, CD86, STAT3, and CXCR4, involved in viral immune response and three (3) significant modules involved in NOD-like receptor signaling, steroid biosynthesis, and viral infections. These identified DEGs, hub genes, and their respective enriched pathways aid us in understanding the molecular mechanisms of cytokine storms, as well as provide potential gene targets and druggable receptors for the treatment of cytokine storms.