Library-assisted nonlinear blind separation and annotation of pure components from a single 1H nuclear magnetic resonance mixture spectra

Abstract

Due to its capability for high-throughput screening ¹H nuclear magnetic resonance (NMR) spectroscopy is commonly used for metabolite research. The key problem in ¹H NMR spectroscopy of multicomponent mixtures is overlapping of component signals and that is increasing with the number of components, their complexity and structural similarity. It makes metabolic profiling, that is carried out through matching acquired spectra with metabolites from the library, a hard problem. Here, we propose a method for nonlinear blind separation of highly correlated components spectra from a single ¹H NMR mixture spectra. The method transforms a single nonlinear mixture into multiple high-dimensional reproducible kernel Hilbert Spaces (mRKHSs). Therein, highly correlated components are separated by sparseness constrained nonnegative matrix factorization in each induced RKHS. Afterwards, metabolites are identified through comparison of separated components with the library comprised of 160 pure components. Thereby, a significant number of them are expected to be related with diabetes type 2. Conceptually similar methodology for nonlinear blind separation of correlated components from two or more mixtures is presented in the Supplementary material. Single-mixture blind source separation is exemplified on: (i) annotation of five components spectra separated from one ¹H NMR model mixture spectra; (ii) annotation of fifty five metabolites separated from one ¹H NMR mixture spectra of urine of subjects with and without diabetes type 2. Arguably, it is for the first time a method for blind separation of a large number of components from a single nonlinear mixture has been proposed. Moreover, the proposed method pinpoints urinary creatine, glutamic acid and 5-hydroxyindoleacetic acid as the most prominent metabolites in samples from subjects with diabetes type 2, when compared to healthy controls.

Keywords: (1)H NMR spectroscopy; Metabolic profiling; Multiple reproducible kernel Hilbert spaces; Nonlinear blind source separation; Nonnegative sparse matrix factorization; Single mixture.