# The disturbance of ABC transporters in patients with dengue fever: integration of metabolomics and transcriptomics

## TL;DR

This study explores how dengue fever disrupts ABC transporters and metabolic pathways, identifying potential biomarkers and key genes involved in the disease.

## Contribution

The integration of metabolomics and transcriptomics reveals novel insights into ABC transporter disturbances and potential diagnostic biomarkers in dengue fever.

## Key findings

- 61 up-regulated and 136 down-regulated metabolites were identified in dengue patients.
- Top 10 up-regulated metabolites with high AUC values are potential diagnostic biomarkers for dengue fever.
- ABC transporters and related metabolic pathways are significantly disturbed in dengue patients.

## Abstract

DENV virus (DENV) infection can cause various symptoms and organ damage, even severe dengue fever. However, the underlying host response products and interfering metabolic pathways and mechanisms of DENV infection remain unclear. In this study, we characterized the metabolites and metabolic pathway changes during DENV infection using liquid chromatography- (LC-MS) and gas chromatography-mass spectrometry (GC-MS). And identify the hub differentially expressed targets associated with major metabolism pathways combining transcriptomics.

Plasma from adult patients infected with DENV infection was characterized by untargeted metabolomics using LC-MS and GC-MS. Potential diagnostic biomarkers for dengue fever were indicated using ROC curve analysis. KEGG and GSEA functional enrichment analysis was the strategy to determine the mechanisms of key metabolic pathways in dengue fever. Potential targets were identified by combining transcriptomic in Gene Expression Omnibus (GEO) datasets, and gene databases from GeneCards and the Comparative Toxicogenomics Database (CTD).

A total of 41 dengue patients and 23 healthy volunteers were recruited for the study. 61 up-regulated and 136 down-regulated metabolites were identified via untargeted metabolomics. The top10 up-regulated metabolites with high AUC values included trans-cinnamic acid, L-Acetylcarnitine, SM(d17:1/17:0), 1,2,4,5-cyclohexanetetrol, 5-(hydroxymethyl) pyrrolidin-2-one, 1,2,3,4-tetrahydro-6-propanoylpyridine, 2-C-methyl-D-erythritol-4-phosphate, Physalolactone, S-Japonin, and 9-tridecynoic acid, and they were supposed to be the potential diagnostic biomarkers for dengue fever. The disturbance of ATP-binding cassette (ABC) transporters, protein digestion and absorption, aminoacyl-tRNA biosynthesis, mineral absorption, and D-amino acid metabolism were enriched in the metabolic pathways. ABCC5, ABCB1, and ABCG5 were identified as hub differentially expressed targets through transcriptome profiling and protein-protein interaction networks.

The current study revealed a shift in metabolite profiles and disturbance in ABC transporters in dengue fever, which can be used for further functional verification.