Blind separation of analytes in nuclear magnetic resonance spectroscopy: Improved model for nonnegative matrix factorization

We introduce an improved model for sparseness-constrained nonnegative matrix factorization (sNMF) of amplitude nuclear magnetic resonance (NMR) spectra of mixtures into a greater number of component spectra. In the proposed method, the selected sNMF algorithm is applied to the square of the amplitude of the NMR spectrum of the mixture instead of to the amplitude spectrum itself. Afterwards, the square roots of separated squares of the component spectra and the concentration matrix yield estimates of the true component amplitude spectrum and of the concentration matrix. The proposed model remains linear on average when the number of overlapping components is increasing, while the model based on the amplitude spectra of the mixtures deviates from the linear one when the number of overlapping components is increased. This is demonstrated through the conducted sensitivity analysis. Thus, the proposed model improves the capability of the sparse NMF algorithms to separate correlated (overlapping) component spectra from the smaller number of mixture NMR spectra. This is demonstrated in two experimental scenarios: extraction of three correlated component spectra from two H-1 NMR mixture spectra and extraction of four correlated component spectra from three COSY NMR mixture spectra. The proposed method can increase efficiency in a spectral library search by reducing the occurrence of false positives and false negatives. That, in turn, can yield better accuracy in biomarker identification studies, which makes the proposed method important for natural product research and the field of metabolic studies. (C) 2014 Elsevier B.V. All rights reserved.