非靶向与靶向代谢组学在妊娠期糖尿病生物标志物发现中的比较

Comparison of untargeted versus targeted metabolomics for biomarker discovery in gestational diabetes mellitus

目的:比较非靶向与靶向代谢组学在发现妊娠期糖尿病(gestational diabetes mellitus,GDM)生物标志物中的异同。方法:采集20例GDM患者及20例正常孕妇的血清样本,同时进行非靶向代谢组学和靶向代谢组学分析,比较两种技术的质控结果、代谢物检测情况及差异代谢物的诊断效能。结果:两种技术的质量控制均较好,非靶向代谢组学分析的系统稳定性更强。正交-偏最小二乘判别分析模型显示,靶向代谢组学分析的样本分布趋势能更好地区分GDM患者。比较两种方法检测到的代谢物种类,非靶向代谢组学分析检测到639种,主要为脂质,而靶向代谢组学分析仅检测到268种,主要为氨基酸及多肽类似物。靶向代谢组学分析检测到的柠檬酸的诊断效能最高,曲线下面积为0.983。结论:两种技术都可以筛选出具有一定诊断效能的生物标志物,非靶向代谢组学分析可覆盖更广泛的潜在生物标志物,靶向代谢组学分析筛选出的生物标志物具有更高的诊断效能,二者在生物标志物的筛选方面可以优势互补。

Objective:The current study aims to compare the similarities and differences between untargeted and targeted metabolomics in the detection of biomarkers of gestational diabetes mellitus(GDM).Methods:Serum samples were collected from 20 patients with GDM and 20 normal pregnant women.Untargeted metabolomics and targeted metabolomics analyses were performed at the same time to compare the quality control results,metabolite detection and diagnostic efficacy between the two technologies.Results:The quality control of both techniques was good,and the detection system of untargeted metabolomics was more stable.The orthogonal⁃partial least squares⁃discriminant analysis model showed that the sample distribution trend of targeted metabolomics could better differentiate patients with GDM.Comparing the types of metabolites detected by the two methods,the untargeted metabolomics method detected 639,mainly lipids,while the target metabolomics method only detected 268,mainly amino acids and polypeptide analogues.Citric acid detected by targeted metabolomics had the highest diagnostic efficacy with an area under the curve of 0.983.Conclusion:Both technologies can screen out biomarkers with certain diagnostic efficiency,untargeted metabolomics covers a wider range of potential biomarkers,while targeted metabolomics can screen out biomarkers with higher diagnostic efficiency.The two methods have complementary advantages in screening biomarkers.