A Multi-Omics Study Reveals Pathway-Level Insights and Predictive Biomarkers in pediatric TB.

Background: Tuberculosis (TB) remains a global health threat, affecting over a million children under the age of 15 annually. Many children with TB do not receive treatment due to challenges in diagnosis. Methods: We performed a multi-omics analysis for pediatric TB by integrating plasma proteomics and metabolomics data from children with presumptive TB across four high-burden countries. Pathway enrichment analysis was conducted using multiGSEA to identify relevant immune and metabolic pathways. We also applied mixOmics and multiview approaches for diagnostic biomarker discovery and compared the performance of multi-omics signatures with those derived from single-omics datasets. Results: Enrichment analysis revealed several immune and metabolic pathways, including PTEN and RUNX2 regulation pathways, as well as arginine and proline metabolism, that were uniquely identified through data integration. While the multi-omics model showed marginal improvement over single-omics models, proteomics alone generally outperformed metabolomics and demonstrated greater potential for accurately classifying Confirmed TB versus Unlikely TB in children. Conclusion: These findings demonstrate the advantage of combining complementary molecular layers to gain a deeper understanding of disease mechanisms and highlight the potential of proteomics for improving pediatric TB diagnosis.