| Titre : | High-throughput 1H NMR-based metabolic analysis of human serum and urine for large-scale epidemiological studies : validation study. (2008) |
| Auteurs : | Richard-H BARTON ; ELLIOTT (Paul) : GBR. Department of Epidemiology and Public Health. Faculty of Medicine. Imperial College London. St Mary's campus. London. ; Elaine HOLMES ; Jeremy-K NICHOLSON ; Biomolecular Medicine. Sora Division. Faculty of Medicine. Imperial College London. London. GBR |
| Type de document : | Article |
| Dans : | International journal of epidemiology (vol. 37, 2008) |
| Pagination : | I31-I40 |
| Langues: | Anglais |
| Mots-clés : | Homme ; Sérum ; Urine ; Validation |
| Résumé : | [BDSP. Notice produite par INIST-CNRS R0xBCkJB. Diffusion soumise à autorisation]. 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=24h 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=24h urine and serum groups showed no systematic metabolite changes, indicating biochemical stability. Some small differences in serum specimens stored for t=36h 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=24h 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. |
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