A Systems Biology Approach to Identify Shared Genetic Signatures, Macromolecular Interactions, and Evolutionary Relationships between Dengue and Comorbidities

Dengue is a virus spread by mosquitoes, and it now worries health officials everywhere, particularly where clinics and hospitals still struggle to stay open. The illness becomes far heavier to carry when patients already live with diabetes, coronary heart disease, hepatitis, COPD, or chronic kidney disease. Although clinical data suggest worsened outcomes for dengue patients with these conditions, the underlying genetic and molecular mechanisms remain insufficiently understood. In this study, we applied a systems biology approach to explore shared molecular signatures between dengue and its major comorbidities. Differentially expressed genes (DEGs) were identified using the Limma package in R, with Benjamini-Hochberg (BH) correction applied for statistical significance. Shared DEGs across diseases were identified-46 with diabetes, 18 with CHD, 242 with hepatitis, 14 with COPD, and 45 with CKD-and were categorized as up regulated or downregulated. We built gene-disease networks (GDNs) to show where the same molecular machinery goes wrong in dengue and its comorbid conditions. Then we ran pathway and gene ontology enrichment tests through Enrichr, checking the results against Reactome, KEGG, BioCarta, and WikiPathways. Protein-protein and protein-drug interaction maps were drawn in STRING and Cytoscape, revealing several hub genes that act as potential drug targets. Gene expression heatmaps also presented clear patterns of up- and down-regulation across the different disease states. Links between conditions were further confirmed with trusted resources like dbGaP and OMIM. Phylogenetic trees made in MEGA and fed with NCBI FASTA sequences traced the evolutionary paths of dengue and its allies. Together, these findings outline strong molecular and evolutionary connections, opening doors for smarter diagnostics, drug design, and clinical care that considers comorbidity.