Abstract
Personalized medicine is probably the most promising area being developed in modern medicine. This approach attempts to optimize the therapies and the patient care based on the individual patient characteristics. Its success highly depends on the way the characterization of the disease and its evolution, the patient’s classification, its follow-up and the treatment could be optimized. Thus, personalized medicine must combine innovative tools to measure, integrate and model data. Towards this goal, clinical metabolomics appears as ideally suited to obtain relevant information. Indeed, the metabolomics signature brings crucial insight to stratify patients according to their responses to a pathology and/or a treatment, to provide prognostic and diagnostic biomarkers, and to improve therapeutic outcomes. However, the translation of metabolomics from laboratory studies to clinical practice remains a subsequent challenge. Nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) are the two key platforms for the measurement of the metabolome. NMR has several advantages and features that are essential in clinical metabolomics. Indeed, NMR spectroscopy is inherently very robust, reproducible, unbiased, quantitative, informative at the structural molecular level, requires little sample preparation and reduced data processing. NMR is also well adapted to the measurement of large cohorts, to multi-sites and to longitudinal studies. This review focus on the potential of NMR in the context of clinical metabolomics and personalized medicine. Starting with the current status of NMR-based metabolomics at the clinical level and highlighting its strengths, weaknesses and challenges, this article also explores how, far from the initial “opposition” or “competition”, NMR and MS have been integrated and have demonstrated a great complementarity, in terms of sample classification and biomarker identification. Finally, a perspective discussion provides insight into the current methodological developments that could significantly raise NMR as a more resolutive, sensitive and accessible tool for clinical applications and point-of-care diagnosis. Thanks to these advances, NMR has a strong potential to join the other analytical tools currently used in clinical settings.
Highlights
CLINICAL METABOLOMICS AND PERSONALIZED MEDICINEAmongst “omics” approaches, metabolomics is generally presented as the last that appeared in terms of occurrence and development, and as the final biological and biochemical stones in the complex networks of organisms
Reviewed by: Young Hae Choi, Leiden University, Netherlands Benedicte Elena-Herrmann, INSERM U1209 Institut pour l’Avancée des Biosciences (IAB), France Claudio Luchinat, University of Florence, Italy
Thanks to intrinsic properties such as high reproducibility, the possibility to quantify, a high degree of structural information, its “universal” detection capacity for all organic molecules as well as its adaptability in the analysis of biological samples, Nuclear magnetic resonance spectroscopy (NMR) very early appeared as a platform of choice in clinicals metabolomics
Summary
Amongst “omics” approaches, metabolomics is generally presented as the last that appeared in terms of occurrence and development, and as the final biological and biochemical stones in the complex networks of organisms. These networks are highly controlled by several internal and external patient parameters, and the identification and integration of these parameters is essential for a better understanding of the mechanisms that led to the causality and the development of a pathology Since it allows measuring the occurrence and variations of metabolites in organs, tissues and biofluids to be reported in a spatial and temporal manner, clinical metabolomics is to be an essential tool and will play a major role for the search for biomarkers, the identification of biochemical pathways involved in a pathology, the study of the environment and lifestyle influences and the treatment follow-up. The need to better understand and characterize the metabolome, as well as the advent of concepts such as biological systems and metabolic networks and the use of metabolomics in the discovery of disease-specific biomarkers, have made it necessary to increase the number of metabolites identified, especially those present in lower concentrations In this context, mass spectrometry coupled with chromatographic techniques naturally appeared to be the most suitable analytical platform, thanks to its favorable limit of detection. The three following chapters respectively highlight the current position of NMR in clinical metabolomics, the complementarity of NMR with MS and the recent and future developments of NMR in the same field
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