Dataset Information

Combined application of NMR- and GC-MS-based metabonomics yields a superior urinary biomarker panel for bipolar disorder.

ABSTRACT: Bipolar disorder (BD) is a debilitating mental disorder that cannot be diagnosed by objective laboratory-based modalities. Our previous studies have independently used nuclear magnetic resonance (NMR)-based and gas chromatography-mass spectrometry (GC-MS)-based metabonomic methods to characterize the urinary metabolic profiles of BD subjects and healthy controls (HC). However, the combined application of NMR spectroscopy and GC-MS may identify a more comprehensive metabolite panel than any single metabonomic platform alone. Therefore, here we applied a dual platform (NMR spectroscopy and GC-MS) that generated a panel of five metabolite biomarkers for BD-four GC-MS-derived metabolites and one NMR-derived metabolite. This composite biomarker panel could effectively discriminate BD subjects from HC, achieving an area under receiver operating characteristic curve (AUC) values of 0.974 in a training set and 0.964 in a test set. Moreover, the diagnostic performance of this panel was significantly superior to the previous single platform-derived metabolite panels. Thus, the urinary biomarker panel identified here shows promise as an effective diagnostic tool for BD. These findings also demonstrate the complementary nature of NMR spectroscopy and GC-MS for metabonomic analysis, suggesting that the combination of NMR spectroscopy and GC-MS can identify a more comprehensive metabolite panel than applying each platform in isolation.

SUBMITTER: Chen JJ

PROVIDER: S-EPMC5376169 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Combined application of NMR- and GC-MS-based metabonomics yields a superior urinary biomarker panel for bipolar disorder.

Chen Jian-jun JJ Liu Zhao Z Fan Song-hua SH Yang De-yu DY Zheng Peng P Shao Wei-hua WH Qi Zhi-guo ZG Xu Xue-jiao XJ Li Qi Q Mu Jun J Yang Yong-tao YT Xie Peng P

Scientific reports 20140728

Bipolar disorder (BD) is a debilitating mental disorder that cannot be diagnosed by objective laboratory-based modalities. Our previous studies have independently used nuclear magnetic resonance (NMR)-based and gas chromatography-mass spectrometry (GC-MS)-based metabonomic methods to characterize the urinary metabolic profiles of BD subjects and healthy controls (HC). However, the combined application of NMR spectroscopy and GC-MS may identify a more comprehensive metabolite panel than any singl ...[more]

PMID: 25068480

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Project description:BackgroundCalcium deficiency is a global public-health problem. Although the initial stage of calcium deficiency can lead to metabolic alterations or potential pathological changes, calcium deficiency is difficult to diagnose accurately. Moreover, the details of the molecular mechanism of calcium deficiency remain somewhat elusive. To accurately assess and provide appropriate nutritional intervention, we carried out a global analysis of metabolic alterations in response to calcium deficiency.MethodsThe metabolic alterations associated with calcium deficiency were first investigated in a rat model, using urinary metabonomics based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis. Correlations between dietary calcium intake and the biomarkers identified from the rat model were further analyzed to confirm the potential application of these biomarkers in humans.ResultsUrinary metabolic-profiling analysis could preliminarily distinguish between calcium-deficient and non-deficient rats after a 2-week low-calcium diet. We established an integrated metabonomics strategy for identifying reliable biomarkers of calcium deficiency using a time-course analysis of discriminating metabolites in a low-calcium diet experiment, repeating the low-calcium diet experiment and performing a calcium-supplement experiment. In total, 27 biomarkers were identified, including glycine, oxoglutaric acid, pyrophosphoric acid, sebacic acid, pseudouridine, indoxyl sulfate, taurine, and phenylacetylglycine. The integrated urinary metabonomics analysis, which combined biomarkers with regular trends of change (types A, B, and C), could accurately assess calcium-deficient rats at different stages and clarify the dynamic pathophysiological changes and molecular mechanism of calcium deficiency in detail. Significant correlations between calcium intake and two biomarkers, pseudouridine (Pearson correlation, r = 0.53, P = 0.0001) and citrate (Pearson correlation, r = -0.43, P = 0.001), were further confirmed in 70 women.ConclusionsTo our knowledge, this is the first report of reliable biomarkers of calcium deficiency, which were identified using an integrated strategy. The identified biomarkers give new insights into the pathophysiological changes and molecular mechanisms of calcium deficiency. The correlations between calcium intake and two of the biomarkers provide a rationale or potential for further assessment and elucidation of the metabolic responses of calcium deficiency in humans.

Project description:BackgroundBisphenol A (BPA) is typically measured in urine using an indirect method that involves enzymatic deconjugation and extraction. In contrast, the direct method measures free and conjugated BPA concurrently and sums them to estimate urinary BPA concentrations. Statistical comparison of total BPA results using the direct and indirect methods is necessary to accurately interpret biomonitoring data for risk assessments.ObjectivesTo compare urinary BPA concentrations estimated from the indirect and direct methods in duplicate first trimester urine samples collected from 1879 pregnant women from the MIREC Study.MethodsFor the indirect method, we measured urinary BPA concentrations using GC-MS/MS. For the direct method, we summed free and conjugated BPA concentrations measured using LC-MS/MS. We evaluated deviation between the two methods using the Bland-Altman analysis in the total sample and stratified (1) by specific gravity and (2) at the limit of quantification (LOQ).ResultsMedian urinary BPA concentrations for the direct and indirect methods were 0.89 µg BPA equivalents/L and 0.81 µg/L respectively. Concentrations from the direct method were, on average, 8.6% (95% CI: 6.7%, 10.5%) higher than the indirect method in a Bland-Altman analysis. The percent differences between the two methods was 4.0% in urines with specific gravities < 1.02 (n = 1348, 72%) and 20.3% in urine with specific gravity ≥ 1.02. In values below the LOQ (n = 663, 35%), we observed smaller average percent deviation (4.8%) between the two methods but wider limits of agreement.DiscussionResults from this study, based on the largest statistically rigorous comparison of the direct and indirect methods of BPA measurement, contrast previous findings reporting that the indirect method underestimates total BPA exposure. The difference in urinary BPA concentrations we observed with the indirect and direct methods is unlikely to alter the interpretation of health outcome data.

Dataset Information

Combined application of NMR- and GC-MS-based metabonomics yields a superior urinary biomarker panel for bipolar disorder.

Publications

Combined application of NMR- and GC-MS-based metabonomics yields a superior urinary biomarker panel for bipolar disorder.

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