These interactions revealed a strong enrichment of genes in severe, like PI3K-associated immune signaling pathways, including IL-4, and IL-13 signaling, estrogen receptor-mediated signaling, AKT, and VEGF-A and VEGFR2 pathways, which is responsible for the vascular permeability and plasma leakage in severe dengue (Fig 4C-I). Here, ESR1 is linked to dengue disease.