High-throughput 1H NMR-based metabolic analysis of human serum and urine for large-scale epidemiological studies: validation study
1Biomolecular Medicine, SORA Division, Faculty of Medicine, Imperial College London, Exhibition Road, London SW7 2AZ, UK.
2Department of Epidemiology and Public Health, Faculty of Medicine, Imperial College London, St Mary's campus, Norfolk Place, London W2 1PG, UK.
* Corresponding author. Biomolecular Medicine, Faculty of Medicine, Imperial College London, Exhibition Rd, London SW7 2AZ. E-mail: r.barton{at}ic.ac.uk
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Abstract |
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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 1H 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°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°C were easily paired and the split-specimen matching task was reduced to a workable size. 1H 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°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 metabolite was implicated.
Conclusions For the purposes of NMR-based analysis, storage of urine and serum for up to t = 24 h at 4°C does not detectably affect the metabolic profile and the methodology is robust. Future application of multivariate methods to data-rich studies should substantially enhance information recovery from epidemiological studies.
Keywords Metabonomics, urine, serum, NMR, molecular epidemiology, multivariate
Accepted 10 December 2007
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