Identification of toll-like receptor 5 and acyl-CoA synthetase long chain family member 1 as hub genes are correlated with the severe forms of COVID-19 by Weighted gene co-expression network analysis

Since a 25% mortality rate occurred in critical Coronavirus disease 2019 (COVID-19) patients, investigating the potential drivers remains to be important. Here, the authors applied Weighted Gene Co-expression Network Analysis to identify the potential drivers in the blood samples of multiple COVID-19 expression profiles. The authors found that the darkslateblue module was significantly correlated with critical COVID-19, and Gene Ontology analysis indicated terms associated with the inflammation pathway and apoptotic process. The authors intersected differentially expressed genes, Maximal Clique Centrality calculated hub genes, and COVID-19 related genes in the Genecards dataset, and two genes, toll-like receptor 5 (TLR5) and acyl-CoA synthetase long chain family member 1 (ACSL1), were screened out. The Gene Set Enrichment Analysis further supports their core role in the inflammatory pathway. Furthermore, the cell-type identification by estimating relative subsets of RNA transcript demonstrated that TLR5 and ACSL1 were associated with neutrophil enrichment in critical COVID-19 patients. Collectively, the aurthors identified two hub genes that were strongly correlated with critical COVID-19. These may help clarify the pathogenesis and assist the immunotherapy development.