Sex-Specific Extracellular Vesicles Signatures in Alcohol Use Disorder: Insights from Multiomics Integration

Poster presented in the XV Symposium on Bioinformatics – JBI2025Abstract: Recent advances in multiomics integration have accelerated biomarker discovery. Here, we applied an integrated miRNome and lipidome approach to plasma extracellular vesicles (EVs) from individuals with alcohol use disorder (AUD), including both sexes, to gain a comprehensive understanding of the molecular mechanisms underlying AUD. EVs were isolated from the plasma samples of AUD patients and controls. miRNAs and lipids were independently extracted from the same individuals, quantified, processed, and normalized according to omics-specific protocols to ensure suitability for integration. To explore combined molecular alterations, we employed the block.sPLS method (N-integration framework) from the mixOmics R package. The predictor matrix (X) included normalized miRNA and lipid expression values, while the response matrix (Y) encoded experimental groups based on sex and AUD condition. A three-component model with full design was optimized to select the most discriminative features. We identified a robust AUD Signature—20 miRNAs (e.g., hsa-miR-99b-3p) and 20 lipids (e.g., Cer_NDS d39:1)—with potential diagnostic and prognostic utility. Additionally, a Sex-AUD Signature— 10 miRNAs (e.g., hsa-miR-1301-3p) and 10 lipids (e.g., PC 39:4)—revealed distinct alcohol-induced molecular responses in males and females, supporting a sex-informed perspective of AUD pathophysiology. Notably, the strength of these signatures lies in their combined profile rather than in individual features. This is the first study to integrate EV-derived miRNA and lipid data in AUD, revealing novel sex-related molecular networks. Our findings highlight the added value of multiomics integration for identifying clinically relevant signatures and advancing precision medicine.https://carpercle.shinyapps.io/SexEVEthOmics/