Today, Bénédicte Buffin-Meyer presented her work on urinary metabolome analysis by CE-MS to discover metabolite-based biomarkers of UPJ obstruction and the 10th meeting of the French metabolomics network in Montpellier (http://10-js-rfmf.sciencesconf.org/).
Most metabolomics studies use nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography coupled to mass spectroscopy (LC/MS). In contrast, capillary electrophoresis coupled to mass spectrometry (CE/MS) has been rarely used for metabolome analysis due to issues related to stable coupling of CE to the MS instrument and the limited loading capacity of CE columns.
Here, we report an optimized CE/MS setup and data analysis pipeline that allows comparing the metabolite content in urine samples analyzed over a period of several years. A novel normalization procedure using endogenous stable urinary metabolites was developed based on the combined metabolome of 75 different urine samples from healthy and disease individuals. Using this new normalization procedure, the CE/MS platform displayed high performance in terms of long-term stability as it allowed comparison of the same sample analyzed nearly 130 times over a range of 4 years. Next we evaluated the clinical utility of the CE/MS pipeline for the discovery of urinary metabolite biomarkers for diagnosis of obstructive nephropathy in infants. We compared the urine metabolome of 34 newborns with ureteropelvic junction (UPJ) obstruction and 15 healthy newborns. This led to the identification of 32 differentially excreted metabolite features. When combined in a SVM classifier, these 32 metabolites predicted with 88% sensibility and 86% specificity whether a new sample belonged to the UPJ obstruction or healthy group in a separate validation cohort of 24 individuals.