@article{366d2ce787804df0b6e1aafbd3058994,
title = "NMR and Metabolomics—A Roadmap for the Future",
abstract = "Metabolomics investigates global metabolic alterations associated with chemical, biological, physiological, or pathological processes. These metabolic changes are measured with various analytical platforms including liquid chromatography-mass spectrometry (LC-MS), gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR). While LC-MS methods are becoming increasingly popular in the field of metabolomics (accounting for more than 70% of published metabolomics studies to date), there are considerable benefits and advantages to NMR-based methods for metabolomic studies. In fact, according to PubMed, more than 926 papers on NMR-based metabolomics were published in 2021—the most ever published in a given year. This suggests that NMR-based metabolomics continues to grow and has plenty to offer to the scientific community. This perspective outlines the growing applications of NMR in metabolomics, highlights several recent advances in NMR technologies for metabolomics, and provides a roadmap for future advancements.",
keywords = "NMR spectroscopy, advances, imaging, metabolomics, review",
author = "Wishart, {David S.} and Cheng, {Leo L.} and Val{\'e}rie Copi{\'e} and Edison, {Arthur S.} and Eghbalnia, {Hamid R.} and Hoch, {Jeffrey C.} and Gouveia, {Goncalo J.} and Wimal Pathmasiri and Robert Powers and Schock, {Tracey B.} and Sumner, {Lloyd W.} and Mario Uchimiya",
note = "Funding Information: NMR is the gold standard for establishing molecular connectivity and three-dimensional structures of small molecules. While its relatively lower sensitivity is often considered an Achilles{\textquoteright} heel, NMR sensitivity has significantly improved over the past couple of decades. The advent and advancement of very high field magnets have brought about significant improvements in sensitivity, which is non-linearly proportional to the magnetic field strength. Increased magnetic fields also provide improvements in spectral resolution and the simplification of scalar couplings, which can improve the accuracy of spectral deconvolution and thus also improve sensitivity. Most research-intensive universities have multiple high-field (e.g., 500 to 900 MHz) NMR instruments, while ultra-high field instruments (e.g., >900 MHz) are becoming accessible via shared resource centers. For example, the highest field NMR instrument, a 1.5 GHz instrument located at the USA National High Magnetic Field Laboratory (Tallahassee, FL, USA), is now available (~20 weeks, only short-duration experiments). Likewise, the National Science Foundation (NSF) has recently funded a 1.2 GHz instrument at Ohio State University and two NSF-funded 1.1 GHz instruments will be available through the Network for Advanced Nuclear Magnetic Resonance (NAN) and located at the University of Wisconsin, Madison and the University of Georgia, Athens. Despite the clear importance and growing need for ultra-high field instruments by the NMR community, the US lags in the acquisition of GHz instruments, whereas more than ten 1.2 GHz instruments have been delivered or are on order throughout Europe, including Florence (CERM), Italy, Zurich, Switzerland, Grenoble, France, and Utrecht, Netherlands. Many of these instruments are beginning to be used in metabolomics applications, as they often double the number of metabolites that can be detected and quantified relative to more conventional (500–600 MHz) magnets. provides a comparison of experimental data collected at 700 MHz and 1.1 GHz using the same sample of human urine. The increased spectral dispersion at 1.1 GHz resolves many overlapping regions where multiplet structures were ambiguous at 700 MHz. Spectra improve at higher field for several reasons: First, the coupling (in Hz) is independent of field strength, while the chemical shifts (in Hz) are proportional to field strength. Consequently, multiplets appear narrower and thus better resolved at higher field strength. The second very important effect is a reduction of strong coupling, which distorts resonances when the chemical shift difference between two coupled nuclei is close to the size of their coupling. also reveals several peaks observable at 1.1 GHz that are too small to interpret at 700 MHz. This is not surprising, because urine contains thousands of metabolites, many of which fall below the limits of detection in lower-field NMR. Thus, using GHz-class instruments for 1D metabolomics analysis will result in more quantified metabolites in a metabolomics study. Thus, to further enable advances in NMR-based metabolomics, we encourage US funding agencies to continue to support and prioritize the acquisition of GHz NMR instruments to increase their accessibility to the metabolomics community. Funding Information: This research was funded by NIH AG070257 and CA243255 (to L.L.C.), NIH U2CES030167 and NSF 1946970 (to A.S.E.), NIH R01DK117473 and NSF MCB-1714556 (to V.C.), NIH R01GM109046 and P41GM111135 (to J.C.H. and H.R.E.) NSF 1660921 (to R.P.), NIH R01AI148160 (to R.P.) and the Nebraska Center for Integrated Biomolecular Communication (NIH P20 GM113126). L.W.S. acknowledges current financial support from NCCIH 5U24AT010811-02, NIFA 2021-51181-35860, and NIH R01AI162321. Publisher Copyright: {\textcopyright} 2022 by the authors.",
year = "2022",
month = aug,
doi = "10.3390/metabo12080678",
language = "English (US)",
volume = "12",
journal = "Metabolites",
issn = "2218-1989",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "8",
}