ABSTRACT
One-dimensional (1D) proton-nuclear magnetic resonance (1 H-NMR) spectroscopy is an established technique for the deconvolution of complex biological sample types via the identification/quantification of small molecules. It is highly reproducible and could be easily automated for small to large-scale bioanalytical, epidemiological, and in general metabolomics studies. However, chemical shift variability is a serious issue that must still be solved in order to fully automate metabolite identification. Herein, we demonstrate a strategy to increase the confidence in assignments and effectively predict the chemical shifts of various NMR signals based upon the simplest form of statistical models (i.e., linear regression). To build these models, we were guided by chemical homology in serum/plasma metabolites classes (i.e., amino acids and carboxylic acids) and similarity between chemical groups such as methyl protons. Our models, built on 940 serum samples and validated in an independent cohort of 1,052 plasma-EDTA spectra, were able to successfully predict the 1 H NMR chemical shifts of 15 metabolites within ~1.5 linewidths (Δv1/2 ) error range on average. This pilot study demonstrates the potential of developing an algorithm for the accurate assignment of 1 H NMR chemical shifts based solely on chemically defined constraints.
