Janeckova Hana, Kalivodova Alzbeta, Najdekr Lukas, Friedecky David, Hron Karel, Bruheim Per, Adam Tomas
Laboratory for Inherited Metabolic Disorders, Department of Clinical Biochemistry, University Hospital Olomouc, Czech Republic.
Laboratory of Metabolomics, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2015 Dec;159(4):582-5. doi: 10.5507/bp.2014.048. Epub 2014 Nov 7.
Metabolomics is becoming an important tool in clinical research and the diagnosis of human diseases. It has been used in the diagnosis of inherited metabolic disorders with pronounced biochemical abnormalities. The aim of this study was to determine if it could be applied in the diagnosis of inherited metabolic disorders (IMDs) with less clear biochemical profiles from urine samples using an untargeted metabolomic approach.
A total of 14 control urine samples and 21 samples from infants with cystinuria, maple syrup urine disease, adenylosuccinate lyase deficiency and galactosemia were tested. Samples were analyzed by liquid chromatography on aminopropyl column in aqueous normal phase separation system using gradient elution of acetonitrile/ammonium acetate. Detection was performed by time-of-flight mass spectrometer fitted with electrospray ionisation in positive mode. The data were statistically processed using principal component analysis (PCA), principal component discriminant function analysis (PCA-DFA) and partial least squares (PLS) regression.
All patient samples were first distinguished from controls using unsupervised PCA. Discrimination of the patient samples was then unambiguously verified using supervised PCA-DFA. Known markers of the diseases in question were successfully confirmed and a potential new marker emerged from the PLS regression.
This study showed that untargeted metabolomics can be applied in the diagnosis of mild IMDs with less clear biochemical profiles.
代谢组学正成为临床研究和人类疾病诊断中的一项重要工具。它已被用于诊断具有明显生化异常的遗传性代谢紊乱。本研究的目的是确定使用非靶向代谢组学方法，能否根据尿液样本诊断生化特征不太明确的遗传性代谢紊乱（IMD）。
共检测了14份对照尿液样本以及21份来自患有胱氨酸尿症、枫糖尿症、腺苷琥珀酸裂解酶缺乏症和半乳糖血症婴儿的样本。在水相正相分离系统中，采用乙腈/醋酸铵梯度洗脱，通过氨基丙基柱上的液相色谱对样本进行分析。采用配备电喷雾电离的飞行时间质谱仪在正模式下进行检测。使用主成分分析（PCA）、主成分判别函数分析（PCA-DFA）和偏最小二乘（PLS）回归对数据进行统计处理。
首先使用无监督PCA将所有患者样本与对照区分开来。然后使用有监督的PCA-DFA明确验证了患者样本的判别。成功确认了相关疾病的已知标志物，并且从PLS回归中出现了一个潜在的新标志物。
本研究表明，非靶向代谢组学可用于诊断生化特征不太明确的轻度IMD。
