代谢组学分析鉴定儿童脓毒症亚型间的差异代谢物及潜在诊断生物标志物
Metabolomics analysis identifies differential metabolites and potential diagnostic biomarkers among pediatric sepsis subtypes.
摘要(中文译文)
儿童脓毒症可由多种病原体引起，其中细菌和病毒最为常见。本研究采用代谢组学方法识别导致儿童脓毒症的不同病原体之间代谢谱的差异及潜在生物标志物。从MetaboLights数据库（MTBLS563）获取儿童细菌性和病毒性脓毒症的血清代谢组学图谱。采用主成分分析（PCA）、偏最小二乘判别分析（PLS-DA）和正交PLS-DA探讨代谢差异。通过Wilcoxon秩和检验和变量投影重要性（VIP）评分鉴定差异表达代谢物（DEMs）。进行京都基因与基因组百科全书（KEGG）富集分析、受试者工作特征（ROC）分析、极端梯度提升（XGBoost）建模和Shapley加性解释（SHAP）分析，以确定诊断性代谢物并评估模型性能。PCA和PLS-DA揭示了儿童细菌性脓毒症（PBID_PS）、儿童病毒性脓毒症（VID_PS）和健康对照之间存在明显的代谢谱差异。共鉴定出14种差异代谢物，主要富集于氮代谢、精氨酸生物合成以及丙氨酸、天冬氨酸和谷氨酸代谢通路。其中，胆碱、谷氨酸和谷氨酰胺在PBID_PS与VID_PS之间表现出较强的区分能力。XGBoost和SHAP分析证实这些代谢物为关键诊断指标，实现了优异的预测性能，并揭示了儿童脓毒症不同病因下存在的差异性代谢重编程。代谢组学分析揭示了细菌性与病毒性儿童脓毒症之间不同的代谢特征，谷氨酸、谷氨酰胺和胆碱可作为潜在生物标志物。
Abstract
Sepsis in children can be caused by a variety of pathogens, with bacteria and viruses being the most common. This study used metabolomics to identify differences in metabolic profiles and potential biomarkers among pathogens causing pediatric sepsis. Serum metabolomic profiles of pediatric bacterial and viral sepsis were obtained from the MetaboLights database (MTBLS563). Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal PLS-DA were employed to explore metabolic distinctions. Differential expression metabolites (DEMs) were identified using the Wilcoxon rank-sum test and variable importance in projection (VIP) scores. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, receiver operating characteristic (ROC) analysis, Extreme Gradient Boosting (XGBoost) modeling, and Shapley Additive exPlanations (SHAP) analysis were conducted to determine diagnostic metabolites and evaluate model performance. PCA and PLS-DA revealed distinct metabolic profiles among bacterial pediatric sepsis (PBID_PS), viral pediatric sepsis (VID_PS), and healthy controls. Fourteen differential metabolites were identified, primarily enriched in nitrogen metabolism, arginine biosynthesis, and the metabolism of alanine, aspartate, and glutamate. Among them, choline, glutamate, and glutamine exhibited strong discriminatory ability between PBID_PS and VID_PS. XGBoost and SHAP analyses confirmed these metabolites as key diagnostic indicators, achieving excellent predictive performance and revealing distinct metabolic reprogramming underlying different etiologies of pediatric sepsis. Metabolomic profiling revealed distinct metabolic signatures between bacterial and viral pediatric sepsis, with glutamate, glutamine, and choline serving as potential biomarkers.
如何引用
AMA
Sisi Zhuang, Lili Zuo. Metabolomics analysis identifies differential metabolites and potential diagnostic biomarkers among pediatric sepsis subtypes.. PloS one. 2026; doi:10.1371/journal.pone.0351295.
APA
Sisi Zhuang, Lili Zuo (2026). Metabolomics analysis identifies differential metabolites and potential diagnostic biomarkers among pediatric sepsis subtypes.. PloS one. https://doi.org/10.1371/journal.pone.0351295
GB/T 7714
Sisi Zhuang, Lili Zuo. Metabolomics analysis identifies differential metabolites and potential diagnostic biomarkers among pediatric sepsis subtypes.[J]. PloS one, 2026 doi:10.1371/journal.pone.0351295.
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