Recursive segment-wise peak alignment of biological (1)h NMR spectra for improved metabolic biomarker recovery

Anal Chem. 2009 Jan 1;81(1):56-66. doi: 10.1021/ac8011544.


Chemical shift variation in small-molecule (1)H NMR signals of biofluids complicates biomarker information recovery in metabonomic studies when using multivariate statistical and pattern recognition tools. Current peak realignment methods are generally time-consuming or align major peaks at the expense of minor peak shift accuracy. We present a novel recursive segment-wise peak alignment (RSPA) method to reduce variability in peak positions across the multiple (1)H NMR spectra used in metabonomic studies. The method refines a segmentation of reference and test spectra in a top-down fashion, sequentially subdividing the initial larger segments, as required, to improve the local spectral alignment. We also describe a general procedure that allows robust comparison of realignment quality of various available methods for a range of peak intensities. The RSPA method is illustrated with respect to 140 (1)H NMR rat urine spectra from a caloric restriction study and is compared with several other widely used peak alignment methods. We demonstrate the superior performance of the RSPA alignment over a wide range of peaks and its capacity to enhance interpretability and robustness of multivariate statistical tools. The approach is widely applicable for NMR-based metabolic studies and is potentially suitable for many other types of data sets such as chromatographic profiles and MS data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / analysis*
  • Biomarkers / chemistry
  • Biomarkers / urine
  • Caloric Restriction
  • Male
  • Metabolomics / methods*
  • Nuclear Magnetic Resonance, Biomolecular / methods*
  • Rats
  • Rats, Sprague-Dawley
  • Urinalysis / methods


  • Biomarkers