Identification of potential biomarkers in dengue via integrated bioinformatic analysis

Abstract

Dengue fever virus (DENV) is a global health threat that is becoming increasingly critical. However, the pathogenesis of dengue has not yet been fully elucidated. In this study, we employed bioinformatics analysis to identify potential biomarkers related to dengue fever and clarify their underlying mechanisms. The results showed that there were 668, 1901, and 8283 differentially expressed genes between the dengue-infected samples and normal samples in the GSE28405, GSE38246, and GSE51808 datasets, respectively. Through overlapping, a total of 69 differentially expressed genes (DEGs) were identified, of which 51 were upregulated and 18 were downregulated. We identified twelve hub genes, including MX1, IFI44L, IFI44, IFI27, ISG15, STAT1, IFI35, OAS3, OAS2, OAS1, IFI6, and USP18. Except for IFI44 and STAT1, the others were statistically significant after validation. We predicted the related microRNAs (miRNAs) of these 12 target genes through the database miRTarBase, and finally obtained one important miRNA: has-mir-146a-5p. In addition, gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were carried out, and a protein–protein interaction (PPI) network was constructed to gain insight into the actions of DEGs. In conclusion, our study displayed the effectiveness of bioinformatics analysis methods in screening potential pathogenic genes in dengue fever and their underlying mechanisms. Further, we successfully predicted IFI44L and IFI6, as potential biomarkers with DENV infection, providing promising targets for the treatment of dengue fever to a certain extent. Author summary Dengue fever is a mosquito borne viral disease caused by a single stranded RNA virus with four serotypes. DENV infection can cause various diseases, such as breakbone fever, haemorrhagic fever, and shock syndrome. As one of the most viral diseases leading to incidence rate and mortality in animal arthropods, Dengue fever has become an increasingly serious global health threat. However, the pathogenesis of dengue fever has not been fully elucidated. In this study, we used bioinformatics analysis to identify potential biomarkers associated with dengue fever and elucidate their underlying mechanisms. Finally, we predicted that IFI44L and IFI6 might be potential biomarkers of DENV infection. This finding provides a promising target for the treatment of dengue fever to a certain extent. In addition, the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein–protein interaction (PPI) network were implemented to analyze the key differentially expressed genes after DENV infection, and the related mechanisms were illuminated by this study.