2025/12/29 by Chenglin Zhu, Jiaxi Chen, Ying Li +7 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Malaria Research and Control #Metabolomics and Mass Spectrometry Studies #Tuberculosis Research and Epidemiology
paper · doi:10.1002/mco2.70559
openalex publication_date 2025/12/29 · openalex created_date 2025/12/30 · openalex updated_date 2026/07/22
ABSTRACT Tuberculosis (TB) remains a major global health challenge. In this study, we applied UPLC‐MS/MS lipidomics and data‐independent acquisition proteomics to profile plasma from healthy controls, active TB patients, and cured individuals to identify differentially expressed lipids and proteins. Mendelian randomization prioritized phosphatidylcholine (PC) lipids (PC(18:2/18:2), PC(14:0/20:4) and PC(18:0/20:4)) and proteins (haptoglobin [HP], retinol binding protein 4 [RBP4], coagulation factor XIII B subunit [F13B] and inter‐alpha‐trypsin inhibitor heavy chain 1 [ITIH1]) as candidate diagnostic and cure biomarkers. Binary multi‐omics random‐forest classifiers constructed with these markers achieved strong diagnostic (AUC = 0.967, 95% CI: 0.928–1.000) and cure‐monitoring (AUC = 0.981, 95% CI: 0.956–1.000) performance, which was further assessed with ten‐fold cross‐validation. Integration with transcriptomic data and lipid‐related gene analysis provided additional molecular support for HP. Independent validation in the GSE34608 cohort (AUC = 0.965) and ELISA verification (AUC = 0.969) confirmed HP's diagnostic utility at gene and protein levels. GSVA enrichment implicated HP in iron homeostasis and immune response pathways, suggesting a role in Mycobacterium tuberculosis infection and immune evasion through modulation of host iron metabolism. Overall, we present a robust lipid–protein biomarker panel and accurate multi‐omics models for TB diagnosis and monitoring of cure, and propose HP as a promising biomarker and potential therapeutic target. These tools may improve clinical management and treatment evaluation.