High-throughput 1H NMR-based metabolic analysis of human serum and urine for large-scale epidemiological studies: validation study

作者：Richard H. Barton, Jeremy Kirk Nicholson, Paul Elliott, Elaine C. Holmes · 发表于：International Journal of Epidemiology · 年份：2008 · DOI：10.1093/ije/dym284 · 被引用次数：133 · 研究领域：Metabolomics and Mass Spectrometry Studies、Advanced MRI Techniques and Applications、Advanced Proteomics Techniques and Applications

BACKGROUND: Metabolic profiling of biofluid specimens is an established method for investigating disease states in clinical studies but is only recently being applied to large-scale human population studies. As part of protocol development for the UK Biobank study, a (1)H nuclear magnetic resonance (NMR)-based metabonomic analysis of specimen storage effects and analytical reproducibility was carried out using urine and serum specimens from 40 volunteers. METHODS: Aliquots of each specimen were stored for t = 0 and t = 24 h at 4 degrees C prior to freezing, and in the case of serum samples for a further 12 h (t = 36), to determine whether the storage times affected specimen composition and quality. A blinded split-specimen matching exercise was implemented to assign candidate spectral pairs stored for different times using multivariate statistical analysis of the NMR data. RESULTS: Using a chemometric strategy, split specimens at time t = 0 and t = 24 or 36 h after storage at 4 degrees C were easily paired and the split-specimen matching task was reduced to a workable size. (1)H NMR profiling established that the t = 24 h urine and serum groups showed no systematic metabolite changes, indicating biochemical stability. Some small differences in serum specimens stored for t = 36 h at 4 degrees C were detectable only by multivariate analysis, and were attributed to generalized alterations in proteins and protein fragments, and possibly trimethylamine-N-oxide. No other specific m...