Poster Presentation AUS-oMicS 2025

Multi-Platform Proteomic Analysis for Early Plasma Leakage Biomarker Discovery in Dengue Infection (#216)

Samaneh Moallemi 1 2 , Anne Poljak 1 , Nicodemus Tedla 1 , Chathurani Sigera 3 , Praveen Weeratunga 3 , Deepika Fernando 3 , Senaka Rajapakse 3 , Andrew Lloyd 2 , Chaturaka Rodrigo 1 2
  1. School of Biomedical Sciences, Faculty of Medicine, University of New South Wales, Sydney, NSW,2052, Australia
  2. Viral Immunology Systems Program, Kirby Institute, UNSW, Sydney, NSW, 2052, Australia
  3. Faculty of Medicine, University of Colombo, 25, Kynsey Road, CO008, Colombo, Sri Lanka

Background: Dengue infection remains a significant global health concern, with plasma leakage being a critical determinant of disease severity. Early identification of patients at risk for plasma leakage within the first 96 hours of fever remains challenging, highlighting the need for reliable early-stage biomarkers.

Methods: A nested case-control discovery proteomics study was conducted using plasma samples from the Colombo Dengue Study (Sri Lanka). The study included pooled plasma samples from seven groups: plasma leakage positive/negative with/without previous dengue infection (n=50 each), severe dengue (n=22), healthy controls (n=6), and non-dengue fever controls (n=50). A dual-platform approach was employed: discovery phase using DDA LC-MS/MS analyzed through Fragpipe complemented by using SomaScan aptamer-based proteomics.

Results: LC-MS/MS analysis identified 2,022 proteins, with 1,656 also detected by SomaScan. Differential expression analysis revealed 170 proteins significantly altered in the FragPipe analysis (p≤0.1) and 2,020 in SomaScan. Cross-platform validation identified 33 proteins consistently differentially expressed in both platforms (p≤0.1 in FragPipe, p≤0.5 in SomaScan, with consistent fold-change direction). While protein-protein interaction analysis indicated that these proteins do not form a highly interconnected network (PPI enrichment p=0.389), functional enrichment analysis revealed significant associations with extracellular exosomes, extracellular space, vesicles, and cytosol. The enriched tissue terms highlighted particular relevance to liver and hematopoietic system functions.

Conclusion: This comprehensive proteomics analysis identified potential early biomarkers for dengue-associated plasma leakage, with 33 proteins validated across two independent platforms. The enrichment of proteins involved in extracellular processes suggests potential mechanisms for plasma leakage and identifies promising circulating biomarker candidates. These findings provide a foundation for developing early risk stratification tools in dengue infection management.