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Molecular perturbations in pulmonary tuberculosis patients identified by pathway-level analysis of plasma metabolic featuresopen access

Authors
Nguyen Phuoc LongDa Young HeoPark, SeongohNguyen Thi Hai YenCho, Yong-SoonShin, Jae-GookOh, Jee YounKim, Dong-Hyun
Issue Date
24-1월-2022
Publisher
PUBLIC LIBRARY SCIENCE
Citation
PLOS ONE, v.17, no.1
Indexed
SCIE
SCOPUS
Journal Title
PLOS ONE
Volume
17
Number
1
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/141986
DOI
10.1371/journal.pone.0262545
ISSN
1932-6203
Abstract
Insight into the metabolic biosignature of tuberculosis (TB) may inform clinical care, reduce adverse effects, and facilitate metabolism-informed therapeutic development. However, studies often yield inconsistent findings regarding the metabolic profiles of TB. Herein, we conducted an untargeted metabolomics study using plasma from 63 Korean TB patients and 50 controls. Metabolic features were integrated with the data of another cohort from China (35 TB patients and 35 controls) for a global functional meta-analysis. Specifically, all features were matched to a known biological network to identify potential endogenous metabolites. Next, a pathway-level gene set enrichment analysis-based analysis was conducted for each study and the resulting p-values from the pathways of two studies were combined. The meta-analysis revealed both known metabolic alterations and novel processes. For instance, retinol metabolism and cholecalciferol metabolism, which are associated with TB risk and outcome, were altered in plasma from TB patients; proinflammatory lipid mediators were significantly enriched. Furthermore, metabolic processes linked to the innate immune responses and possible interactions between the host and the bacillus showed altered signals. In conclusion, our proof-of-concept study indicated that a pathway-level meta-analysis directly from metabolic features enables accurate interpretation of TB molecular profiles.
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