Interferon gamma and inflammatory response genes by weighted gene co-expression network analysis reveal significant associations with severe dengue infection in India

Objective: Dengue virus, with four serotypes (DENV 1-4), is transmitted by Aedes aegypti . India carries 34% of global cases, yet studies to understand how the immune system reacts to dengue infection remain limited. Design: This study uncovers early transcriptional signatures from whole blood of 112 NS1 positive hospital reported dengue patients and dissect biological processes linked to varying disease severities “with (WS ) and without (-WS ) warning signs”. Results: Differential gene expression analysis showed suppressed innate response in WS patients, with downregulated cytokines ( CXCL8, CXCL16, CXCL2, IL1B) and disrupted platelet function. Upregulation was observed in genes related to glycosylation, nervous system, and metabolism. WGCNA module-trait analysis identified interferon response and inflammation as positively correlated with platelet count, highlighting key genes, IFI44L , IFI35 , OAS1 , HERC6 and SAMDL9 contributing to comparative severe outcomes. CTTN involved in maintenance of vascular permeability showed highest significant association with low platelet count. IFI44L emerged as a significant marker, showing highest transcript count difference between patients with platelet counts below 100 × 10^9/L and those between 100 and 140 × 10^9/L. Conclusion: This study advances understanding of dengue infection and identifying probable clinical biomarkers at the initial phase of infection. These findings might hold potential for improving diagnostic and therapeutic strategies.