Optimization of human plasma 1H NMR spectroscopic data processing for high-throughput metabolic phenotyping studies and detection of insulin resistance related to type 2 diabetes

Anal Chem. 2008 Oct 1;80(19):7354-62. doi: 10.1021/ac801053g. Epub 2008 Aug 30.

Abstract

Optimizing NMR experimental parameters for high-throughput metabolic phenotyping requires careful examination of the total biochemical information obtainable from (1)H NMR data, which includes concentration and molecular dynamics information. Here we have applied two different types of mathematical transformation (calculation of the first derivative of the NMR spectrum and Gaussian shaping of the free-induction decay) to attenuate broad spectral features from macromolecules and enhance the signals of small molecules. By application of chemometric methods such as principal component analysis (PCA), orthogonal projections to latent structures discriminant analysis (O-PLS-DA) and statistical spectroscopic tools such as statistical total correlation spectroscopy (STOCSY), we show that these methods successfully identify the same potential biomarkers as spin-echo (1)H NMR spectra in which broad lines are suppressed via T2 relaxation editing. Finally, we applied these methods for identification of the metabolic phenotype of patients with type 2 diabetes. This "virtual" relaxation-edited spectroscopy (RESY) approach can be particularly useful for high-throughput screening of complex mixtures such as human plasma and may be useful for extraction of latent biochemical information from legacy or archived NMR data sets for which only standard 1D data sets exist.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 2 / blood*
  • Discriminant Analysis
  • Fourier Analysis
  • Glucose Tolerance Test
  • Humans
  • Insulin Resistance / physiology*
  • Nuclear Magnetic Resonance, Biomolecular / methods*
  • Phenotype
  • Principal Component Analysis