1H NMR-based metabonomics for the diagnosis of inborn errors of metabolism in urine
1H NMR-based metabonomics for the diagnosis of inborn errors of metabolism in urine
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DOI：
10.1016/j.aca.2005.03.059
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发表时间：
2005-06-29
影响因子：
6.2
通讯作者：
Mikros, E
中科院分区：
文献类型：
--
作者：
Constantinou, MA;Papakonstantinou, E;Mikros, E
应用基于H-1核磁共振的代谢组学技术对尿液中的先天性代谢缺陷进行检测和诊断。本文对47例正常新生儿、9例苯丙酮尿症（PKU）新生儿和1例枫糖尿症（MSUD）新生儿的1DH-1 NMR谱进行了研究。正常，PKU和MSUD样品的尿H-1 NMR谱表现出关于苯丙氨酸（Phe）和支链氨基酸（亮氨酸，缬氨酸，异亮氨酸）共振的差异，分别。应用主成分分析（PCA）和偏最小二乘判别分析（PLS-DA），以建立适当的模型来区分病理和正常样本。光谱的归一化基于总光谱强度或肌酸酐峰。使用了不同的数据转换程序。通过PCA和PLS-DA建立的不同模型对PKU和MSUD样本与正常样本进行区分，比较两种统计分析方法，发现PLS-DA对所有病理样本的区分效果最好。而PCA被证明适合于识别生理样本中的每一个单个病理样本。因此，尿中的H-1 NMR可以被认为是血斑的替代品，以开发一种大规模筛查方法，该方法不需要样品预处理，并避免了新生儿的任何痛苦的过程。(c)2005 Elsevier B. V.保留所有权利。
H-1 NMR-based metabonomics was used for the detection and diagnosis of inborn errors of metabolism from urine samples. ID H-1 NMR spectra from 47 normal, 9 phenylketonuric (PKU) newborns and I maple syrup urine disease (MSUD) child were obtained and investigated. Urine H-1 NMR spectra of normal, PKU and MSUD samples exhibited differences concerning the phenylalanine (Phe) and branched-chain amino acids (leucine, valine, isoleucine) resonances, respectively. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were applied in order to establish adequate models for discrimination between pathological and normal samples. Normalization of the spectra was based to the total spectral intensity or to creatinine peak. Different data transformation procedures were used. Discrimination of PKU and MSUD samples from normal samples was achieved by the different models produced by PCA and PLS-DA. Comparing the two methods of statistical analysis, PLS-DA was found to lead to a most proper discrimination when all pathological samples were used. while PCA proved suitable to identify every single pathological sample among the physiological ones. Thus, H-1 NMR in urine can be considered as an alternative to blood spots in order to develop a mass-screening method, which does not require sample pre-treatment and avoids any painful procedure for the newborns. (c) 2005 Elsevier B.V. All rights reserved.