Integrated clinical and metabolomic analysis of dengue infection shows molecular signatures associated with host-pathogen interaction in different phases of the disease.

ABSTRACT

PURPOSE: Dengue is a mosquito vector-borne disease caused by the dengue virus, which affects 125 million people globally. The disease causes considerable morbidity. The disease, based on symptoms, is classified into three characteristic phases, which can further lead to complications in the second phase. Molecular signatures that are associated with the three phases have not been well characterized. We performed an integrated clinical and metabolomic analysis of our patient cohort and compared it with omics data from the literature to identify signatures unique to the different phases. METHODS: The dengue patients are recruited by clinicians after standard-of-care diagnostic tests and evaluation of symptoms. Blood from the patients was collected. NS1 antigen, IgM, IgG antibodies, and cytokines in serum were analyzed using ELISA. Targeted metabolomics was performed using LC-MS triple quad. The results were compared with analyzed transcriptomic data from the GEO database and metabolomic data sets from the literature. RESULTS: The dengue patients displayed characteristic features of the disease, including elevated NS1 levels. TNF-α was found to be elevated in all three phases compared to healthy controls. The metabolic pathways were found to be deregulated compared to healthy controls only in phases I and II of dengue patients. The pathways represent viral replication and host response mediated pathways. The major pathways include nucleotide metabolism of various amino acids and fatty acids, biotin, etc. CONCLUSION: The results show elevated TNF-α and metabolites that are characteristic of viral infection and host response. IL10 and IFN-γ were not significant, consistent with the absence of any complications.