Precision High-Throughput Proton NMR Spectroscopy of Human Urine, Serum, and Plasma for Large-Scale Metabolic Phenotyping

被引:393
作者
Dona, Anthony C. [1 ,3 ]
Jimenez, Beatriz [1 ,4 ]
Schaefer, Hartmut [2 ]
Humpfer, Eberhard [2 ]
Spraul, Manfred [2 ]
Lewis, Matthew R. [1 ,3 ]
Pearce, Jake T. M. [1 ,3 ]
Holmes, Elaine [1 ]
Lindon, John C. [1 ]
Nicholson, Jeremy K. [1 ,3 ,4 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, Div Computat & Syst Med, Dept Surg & Canc, London SW7 2AZ, England
[2] Bruker Biospin GmbH, D-76287 Rheinstetten, Germany
[3] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, MRC NIHR Natl Phenome Ctr, London W12 0NN, England
[4] Univ London Imperial Coll Sci Technol & Med, St Marys Hosp, Imperial Clin Phenotypng Ctr, London W2 1NY, England
基金
英国医学研究理事会;
关键词
NUCLEAR-MAGNETIC-RESONANCE; HIGH-RESOLUTION H-1-NMR; ANALYTICAL REPRODUCIBILITY; METABONOMIC TOXICOLOGY; PATTERN-RECOGNITION; DISEASE RISK; BLOOD; TOXICITY; RATS; H-1;
D O I
10.1021/ac5025039
中图分类号
O65 [分析化学];
学科分类号
070302 [分析化学];
摘要
Proton nuclear magnetic resonance (NMR)-based metabolic phenotyping of urine and blood plasma/serum samples provides important prognostic and diagnostic information and permits monitoring of disease progression in an objective manner. Much effort has been made in recent years to develop NMR instrumentation and technology to allow the study of general population samples from epidemiological collections for biomarkers of disease risk. The challenge remains to develop highly reproducible methods and standardized protocols that minimise technical or experimental bias, allowing realistic interlaboratory comparisons of subtle biomarker information. Here we present a detailed set of updated protocols that carefully consider major experimental conditions, including sample preparation, spectrometer parameters, NMR pulse sequences throughput reproducibility quality control, and resolution. These results provide an experimental platform that facilitates NMR spectroscopy usage across different large cohorts of biofluid samples enabling integration of global metabolic profiling that is a prerequiste for personalized healthcare.
引用
收藏
页码:9887 / 9894
页数:8
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