title: Statistical correlation and projection methods for improved information recovery from diffusion-edited NMR spectra of biological samples.
abstract: Although NMR spectroscopic techniques coupled with multivariate statistics can yield much useful information for classifying biological samples based on metabolic profiles, biomarker identification remains a time-consuming and complex procedure involving separation methods, two-dimensional NMR, and other spectroscopic tools. We present a new approach to aid complex biomixture analysis that combines diffusion ordered (DO) NMR spectroscopy with statistical total correlation spectroscopy (STOCSY) and demonstrate its application in the characterization of urinary biomarkers and enhanced information recovery from plasma NMR spectra. This method relies on calculation and display of the covariance of signal intensities from the various nuclei on the same molecule across a series of spectra collected under different pulsed field gradient conditions that differentially attenuate the signal intensities according to translational molecular diffusion rates. We term this statistical diffusion-ordered spectroscopy (S-DOSY). We also have developed a new visualization tool in which the apparent diffusion coefficients from DO spectra are projected onto a 1D NMR spectrum (diffusion-ordered projection spectroscopy, DOPY). Both methods either alone or in combination have the potential for general applications to any complex mixture analysis where the sample contains compounds with a range of diffusion coefficients.
authors.affiliation: Department of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology & Anaesthetics, Faculty of Medicine, Imperial College London, London, SW7 2AZ, UK.
authors.forename: Leon M
authors.initials: LM
authors.lastname: Smith
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Maher
authors.forename: Olivier
authors.initials: O
authors.lastname: Cloarec
authors.forename: Mattias
authors.initials: M
authors.lastname: Rantalainen
authors.forename: Huiru
authors.initials: H
authors.lastname: Tang
authors.forename: Paul
authors.initials: P
authors.lastname: Elliott
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Stamler
authors.forename: John C
authors.initials: JC
authors.lastname: Lindon
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
mesh_terms: D000596:Amino Acids / Q000032:analysis*; D015415:Biomarkers / Q000032:analysis; D002241:Carbohydrates / Q000032:analysis*; D004058:Diffusion; D006801:Humans; D008074:Lipoproteins / Q000097:blood*; D009682:Magnetic Resonance Spectroscopy; D015233:Models, Statistical; D012680:Sensitivity and Specificity; D013997:Time Factors
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D002241:Carbohydrates; D008074:Lipoproteins