ASICS: an automatic method for identification and quantification of metabolites in complex 1D 1H NMR spectra

Abstract

Experiments in metabolomics rely on the identification and quantification of metabolites in complex biological mixtures. This remains one of the major challenges in NMR/mass spectrometry analysis of metabolic profiles. These features are mandatory to make metabolomics asserting a general approach to test a priori formulated hypotheses on the basis of exhaustive metabolome characterization rather than an exploratory tool dealing with unknown metabolic features. In this article we propose a method, named ASICS, based on a strong statistical theory that handles automatically the metabolites identification and quantification in proton NMR spectra. A statistical linear model is built to explain a complex spectrum using a library containing pure metabolite spectra. This model can handle local or global chemical shift variations due to experimental conditions using a warping function. A statistical lasso-type estimator identifies and quantifies the metabolites in the complex spectrum. This estimator shows good statistical properties and handles peak overlapping issues. The performances of the method were investigated on known mixtures (such as synthetic urine) and on plasma datasets from duck and human. Results show noteworthy performances, outperforming current existing methods. ASICS is a completely automated procedure to identify and quantify metabolites in 1H NMR spectra of biological mixtures. It will enable empowering NMR-based metabolomics by quickly and accurately helping experts to obtain metabolic profiles.