Journal
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION
Volume 107, Issue 500, Pages 1259-1271Publisher
AMER STATISTICAL ASSOC
DOI: 10.1080/01621459.2012.695661
Keywords
Block updates; Concentration estimation; Metabolomics; Multicomponent model; Prior information
Categories
Funding
- UK BBSRC grant [BB/E020372/1]
- Discovery Grant from the Natural Sciences and Engineering Council of Canada
- Team Grant from the Fonds de recherche du Quebec-Nature et technologies
- BBSRC [BB/E020372/1] Funding Source: UKRI
- MRC [MC_UP_0801/1] Funding Source: UKRI
- Medical Research Council [MC_UP_0801/1] Funding Source: researchfish
Ask authors/readers for more resources
Nuclear magnetic resonance (NMR) spectra are widely used in metabolomics to obtain profiles of metabolites dissolved in biofluids such as cell supernatants. Methods for estimating metabolite concentrations from these spectra are presently confined to manual peak fitting and to binning procedures for integrating resonance peaks. Extensive information on the patterns of spectral resonance generated by human metabolites is now available in online databases. By incorporating this information into a Bayesian model, we can deconvolve resonance peaks from a spectrum and obtain explicit concentration estimates for the corresponding metabolites. Spectral resonances that cannot be deconvolved in this way may also be of scientific interest; so, we-model them jointly using wavelets. We describe a Markov chain Monte Carlo algorithm that allows us to sample from the joint posterior distribution of the model parameters, using specifically deigned block updates to improve mixing. The strong prior on resonance patterns allows the algorithm to identify peaks corresponding to particular metabolites automatically, eliminating the need for manual peak assignment. We assess our method for peak alignment and concentration estimation. Except in cases when the target resonance signal is very weak, alignment is unbiased and precise. We compare the Bayesian concentration estimates with those obtained from a conventional numerical integration-method and find that our point estimates have six-fold lower mean squared error. Finally, we apply our method to a spectral dataset taken from an investigation of the metabolic response of yeast to recombinant protein expression. We estimate the concentrations of 26 metabolites and compare with manual quantification by five expert spectroscopists. We discuss the reason for discrepancies and the robustness of our method's concentration estimates. This article has supplementary materials online.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available