Comprehensive lipid and lipid-related gene investigations of host immune responses to characterize metabolism-centric biomarkers for pulmonary tuberculosis

Abstract

Despite remarkable success in the prevention and treatment of tuberculosis (TB), it remains one of the most devastating infectious diseases worldwide. Management of TB requires an efficient and timely diagnostic strategy. In this study, we comprehensively characterized the plasma lipidome of TB patients, then selected candidate lipid and lipid-related gene biomarkers using a data-driven, knowledge-based framework. Among 93 lipids that were identified as potential biomarker candidates, ether-linked phosphatidylcholine (PC O–) and phosphatidylcholine (PC) were generally upregulated, while free fatty acids and triglycerides with longer fatty acyl chains were downregulated in the TB group. Lipid-related gene enrichment analysis revealed significantly altered metabolic pathways (e.g., ether lipid, linolenic acid, and cholesterol) and immune response signaling pathways. Based on these potential biomarkers, TB patients could be differentiated from controls in the internal validation (random forest model, area under the curve [AUC] 0.936, 95% confidence interval [CI] 0.865–0.992). PC(O-40:4), PC(O-42:5), PC(36:0), and PC(34:4) were robust biomarkers able to distinguish TB patients from individuals with latent infection and healthy controls, as shown in the external validation. Small changes in expression were identified for 162 significant lipid-related genes in the comparison of TB patients vs. controls; in the random forest model, their utilities were demonstrated by AUCs that ranged from 0.829 to 0.956 in three cohorts. In conclusion, this study introduced a potential framework that can be used to identify and validate metabolism-centric biomarkers.

Lysophosphatidylcholine Acetyltransferase 2 (LPCAT2) Influences the Gene Expression of the Lipopolysaccharide Receptor Complex in Infected RAW264.7 Macrophages, Depending on the E. coli Lipopolysaccharide Serotype

“…Moreover, LPCAT2 has been implicated as a biomarker for inflammatory disorders such as cedar pollen allergenic rhinitis [31], pneumonia [32], and pulmonary tuberculosis [33]. All these publications support evidence that LPCAT2 is pro-inflammatory; however, data on the effect of LPCAT2 on various pro-inflammatory molecules are unavailable.…”

Push forward LC-MS-based therapeutic drug monitoring and pharmacometabolomics for anti-tuberculosis precision dosing and comprehensive clinical management

“…Horizontal (metabolomics and lipidomics) and vertical (genomics, transcriptomics, proteomics, and metabolomics) multi-omics data integration present a powerful approach to capture a holistic view of the molecular landscape, which could provide a comprehensive understanding of an individual's response to anti-TB drugs [ 123 , 124 ]. These approaches are described as prospects to improve the better-personalized medicine of TB and allow the discovery of biosignatures for treatment monitoring and clinical outcomes (efficacy and AEs) [ 123 , [125] , [126] , [127] ]. Long et al.…”

Multi-omics phenotyping characterizes molecular divergence underlying different clinical scenarios of inflammatory bowel disease

“…Metabolomics and lipidomics experiments followed our previously established procedure [23][24][25] . For metabolite extraction, 50 μL of the serum sample (−80 °C) was first thawed on ice for about 30 min and then vortexed extensively for 10 s. Afterward, 150 μL precooled extraction solvent, which was the pre-dissolved of the 6 internal standards in MeOH, was pipetted into each sample.…”

“…The instrumental analysis consisting of the Shimadzu Nexera LC system (Kyoto, Japan) and the X500R Quadrupole Time-of-Flight mass spectrometer combined with Turbo V™ ion source and TwinSpray probe (SCIEX, MA, USA) was utilized [23][24][25] . For metabolomics, ACQUITY UPLC HSS T3 column (50 mm × 2.1 mm; 1.8 μm) coupled with ACQUITY UPLC HSS T3 VanGuard pre-column (5 mm × 2.1 mm; 1.8 μm) was used.…”