A Bayesian Model of NMR Spectra for the Deconvolution and Quantification of Metabolites in Complex Biological Mixtures
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 designed 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.
If you experience problems downloading a file, check if you have the proper application to view it first. In case of further problems read the IDEAS help page. Note that these files are not on the IDEAS site. Please be patient as the files may be large.
As the access to this document is restricted, you may want to look for a different version under "Related research" (further below) or search for a different version of it.
Volume (Year): 107 (2012)
Issue (Month): 500 (December)
|Contact details of provider:|| Web page: http://www.tandfonline.com/UASA20|
|Order Information:||Web: http://www.tandfonline.com/pricing/journal/UASA20|
When requesting a correction, please mention this item's handle: RePEc:taf:jnlasa:v:107:y:2012:i:500:p:1259-1271. See general information about how to correct material in RePEc.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: (Michael McNulty)
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
If references are entirely missing, you can add them using this form.
If the full references list an item that is present in RePEc, but the system did not link to it, you can help with this form.
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your profile, as there may be some citations waiting for confirmation.
Please note that corrections may take a couple of weeks to filter through the various RePEc services.