Public databases of NMR spectra of low molecular weight metabolites must be constructed to remove the major bottleneck of metabolite identification and quantification in the analysis of metabolomics data. Two-dimensional (2-D) 1H J-resolved spectroscopy represents a popular alternative to 1-D NMR methods, resolving the highly overlapped signals characteristic of complex metabolite mixtures across two frequency dimensions. Here we report the design, measurement and curation of, primarily, a database of 2-D J-resolved NMR spectra. Metabolites were selected based upon their importance within metabolic pathways and their detection potential by NMR, and prepared for analysis at pH 6.6, 7.0 and 7.4. Sixteen NMR spectra were recorded for each metabolite using a 500 MHz spectrometer, including 1-D and 2-D J-resolved spectra, different water suppression methods and different acquisition parameters. Some metabolites were removed due to limited solubility, poor NMR signal quality or contamination, and the final dataset comprised of 3328 NMR spectra arising from 208 metabolite standards. These data are housed in a purpose-built MySQL database (Birmingham Metabolite Library; BML-NMR) containing over 100 separate tables and allowing the efficient storage of raw free-induction-decays (FIDs), 1-D and 2-D NMR spectra and associated metadata. The database is compliant with the Metabolomics Standards Initiative (MSI) endorsed reporting requirements, with some necessary amendments. Library data can be accessed freely and searched through a custom written web interface (www.bml-nmr.org). FIDs, NMR spectra and associated metadata can be downloaded according to a newly implemented MSI-compatible XML schema.
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Aue, W. P., Karhan, J., & Ernst, R. R. (1976). Homonuclear broad-band decoupling and 2-dimensional J-resolved NMR spectroscopy. Journal of Chemical Physics, 64, 4226–4227.
Braun, S., Kalinowski, H. O., & Berger, S. (1998). 150 and more basic NMR experiments. Weinheim: Wiley VCH.
Cui, Q., Lewis, I. A., Hegeman, A. D., et al. (2008). Metabolite identification via the Madison Metabolomics Consortium Database. Nature Biotechnology, 26, 162–164.
Fiehn, O., Robertson, D., Griffin, J., et al. (2007). The metabolomics standards initiative (MSI). Metabolomics, 3, 175–178.
Foxall, P. J. D., Parkinson, J. A., Sadler, I. H., Lindon, J. C., & Nicholson, J. K. (1993). Analysis of biological fluids using 600 MHz proton NMR spectroscopy—application of homonuclear 2-dimensional J-resolved spectroscopy to urine and blood plasma for spectral simplification and assignment. Journal of Pharmaceutical and Biomedical, 11, 21–31.
Hines, A., Oladiran, G. S., Bignell, J. P., Stentiford, G. D., & Viant, M. R. (2007). Direct sampling of organisms from the field and knowledge of their phenotype: Key recommendations for environmental metabolomics. Environmental Science and Technology, 41, 3375–3381.
Hwang, T. L., & Shaka, A. J. (1995). Water suppression that works—excitation sculpting using arbitrary wave-forms and pulsed-field gradients. Journal of Magnetic Resonance, Series A, 112, 275–279.
Kanehisa, M., Goto, S., Hattori, M., et al. (2006). From genomics to chemical genomics: New developments in KEGG. Nucleic Acids Research, 34, D354–D357.
Ludwig, C., & Viant, M. R. (2010). Two-dimensional J-resolved NMR spectroscopy: Review of a key methodology in the metabolomics toolbox. Phytochemical Analysis, 21, 22–32.
Lutz, N. W., Maillet, S., Nicoli, F., Viout, P., & Cozzone, P. J. (1998). Further assignment of resonances in H-1 NMR spectra of cerebrospinal fluid (CSF). FEBS Letters, 425, 345–351.
Moore, G. J., & Sillerud, L. O. (1994). The pH-dependence of chemical-shift and spin–spin coupling for citrate. Journal of Magnetic Resonance Series B, 103, 87–88.
Nicholson, J. K., Foxall, P. J. D., Spraul, M., Farrant, R. D., & Lindon, J. C. (1995). 750 MHz H-1 and H-1-C-13 NMR spectroscopy of human blood plasma. Analytical Chemistry, 67, 793–811.
Parsons, H. M., Ludwig, C., Günther, U. L., & Viant, M. R. (2007). Improved classification accuracy in 1- and 2-dimensional NMR metabolomics data using the variance stabilising generalised logarithm transformation. BMC Bioinformatics, 8, 234.
Parsons, H. M., Ludwig, C., & Viant, M. R. (2009). Line-shape analysis of J-resolved NMR spectra: Application to metabolomics and quantification of intensity errors from signal processing and high signal congestion. Magnetic Resonance in Chemistry, 47, S86–S95.
Pence, H. E., & Williams, A. (2010). ChemSpider: An online chemical information resource. Journal of Chemical Education, 87, 1123–1124.
Rubtsov, D. V., Jenkins, H., Ludwig, C., et al. (2007). Proposed reporting requirements for the description of NMR-based metabolomics experiments. Metabolomics, 3, 223–229.
Sumner, L. W., Amberg, A., Barrett, D., et al. (2007). Proposed minimum reporting standards for chemical analysis. Metabolomics, 3, 211–221.
Thrippleton, M. J., Edden, R. A. E., & Keeler, J. (2005). Suppression of strong coupling artefacts in J-spectra. Journal of Magnetic Resonance, 174, 97–109.
Tiziani, S., Lodi, A., Ludwig, C., Parsons, H. M., & Viant, M. R. (2008). Effects of the application of different window functions and projection methods on processing of H-1J-resolved nuclear magnetic resonance spectra for metabolomics. Analytica Chimica Acta, 610, 80–88.
Viant, M. R. (2003). Improved methods for the acquisition and interpretation of NMR metabolomic data. Biochemical and Biophysics Research Communication, 310, 943–948.
Wang, Y. L., Bollard, M. E., Keun, H., et al. (2003). Spectral editing and pattern recognition methods applied to high-resolution magic-angle spinning H-1 nuclear magnetic resonance spectroscopy of liver tissues. Analytical Biochemistry, 323, 26–32.
Wishart, D. S., Tzur, D., Knox, C., et al. (2007). HMDB: The human metabolome database. Nucleic Acids Research, 35, D521–D526.
Xi, Y. X., de Ropp, J. S., Viant, M. R., Woodruff, D. L., & Yu, P. (2006). Automated screening for metabolites in complex mixtures using 2D COSY NMR spectroscopy. Metabolomics, 2, 221–233.
Yang, W. J., Wang, Y. W., Zhou, Q. F., & Tang, H. R. (2008). Analysis of human urine metabolites using SPE and NMR spectroscopy. Science in China Series B: Chemistry, 51, 218–225.
We thank Tony Pemberton for setting up and maintaining the HP server. We thank the BBSRC for funding this research (BB/F016298/1 to MRV and ULG) and the Wellcome Trust for supporting the Henry Wellcome Building for Biomolecular NMR Spectroscopy (083796). This work was also in part supported by the UK Natural Environmental Research Council (NERC) Biomolecular Analysis Facility at the University of Birmingham (R8-H10-61) and by the University of Birmingham’s Systems Science for Health initiative.
Christian Ludwig, John M. Easton were joint first authors.
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Ludwig, C., Easton, J.M., Lodi, A. et al. Birmingham Metabolite Library: a publicly accessible database of 1-D 1H and 2-D 1H J-resolved NMR spectra of authentic metabolite standards (BML-NMR). Metabolomics 8, 8–18 (2012). https://doi.org/10.1007/s11306-011-0347-7
- Metabolite database
- Metabolomics database
- Metabolic pathway