Title : Bioinformatic approaches on differential gene expression in scrub typhus compared to some other acute febrile infections
Concerning the acute febrile infection (AFI) development of improved diagnostics, particularly the molecular diagnostic intervention with therapeutic potential, is an urgent need for infection control and treatment management. Scrub typhus (caused by Orientia tsutsugamushi infection), without eschar development, is a febrile illness that mimics malaria, dengue, and other rickettsioses. Comparative analysis of microarray gene expression profiles of GSE16463 dataset, obtained from Orientia tsutsugamushi infected monocytes, was performed to identify transcriptional signatures in scrub typhus discriminated from other acute febrile infections, accompanied by functional pathways and enrichment analysis in disease pathogenesis. The GSE16463 expression profile was downloaded (www.ncbi.nlm.nih.gov/geo/), extracted with GEO2R tools, PPI network constructed by STRING, modules and hub genes identified using MCODE and CytoHubba plugin of Cytoscape, functional enrichment using GO and Reactome analysis. There were 333 differentially expressed genes (log2FC>1, adjusted p value <0.01) among scrub typhus (n=65+85=150), dengue (n=189+233=422), murine typhus (n=37+27=64), and malaria (n=45+39=84); n = upregulated + downregulated = total genes. Among the genes, 32 were common to all four diseases, and STAT1, ISG15, IFIT3, TRIM21, respectively were the candidate gene of each group. A unique 39 genes belonged to scrub typhus that could be used as signature genes to distinguish scrub typhus from other febrile illnesses compared. The biological process and functional pathways significantly enriched by the scrub typhus genes were respectively for defense response to the pathogens and interferon signaling, which could further help in diagnosis, treatment, and vaccine development as well.