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Biomarker Discovery Using NMR-Based Metabolomics of Tissue

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NMR-Based Metabolomics

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2037))

Abstract

NMR-based metabolomics has shown promise in the diagnosis of diseases as it enables identification and quantification of metabolic biomarkers. Using high-resolution magic-angle-spinning (HR-MAS) NMR spectroscopy, metabolic profiles from intact tissue specimens can be obtained with high spectral resolution. In addition, HR-MAS NMR requires minimal sample preparation and the sample is kept intact for subsequent analyses. In this chapter, we describe a typical protocol for NMR-based metabolomics of tissue samples. We cover all major steps ranging from tissue sample collection to determination of biomarkers, including experimental precautions taken to ensure reproducible and reliable reporting of data in the area of clinical application.

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References

  1. Følling A (1934) Utskillelse av fenylpyrodruesyre i urinen som stoffskifteanomali i forbindelse med imbecillitet. Nord Med 8:1054–1059

    Google Scholar 

  2. Austdal M, Thomsen LC, Tangeras LH, Skei B, Mathew S, Bjorge L, Austgulen R, Bathen TF, Iversen AC (2015) Metabolic profiles of placenta in preeclampsia using HR-MAS MRS metabolomics. Placenta 36(12):1455–1462

    Article  CAS  PubMed  Google Scholar 

  3. Hu JZ, Rommereim DN, Minard KR, Woodstock A, Harrer BJ, Wind RA et al (2008) Metabolomics in lung inflammation:a high-resolution (1)h NMR study of mice exposedto silica dust. Toxicol Mech Methods 18(5):385–398

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Prabakaran S, Swatton JE, Ryan MM, Huffaker SJ, Huang JT, Griffin JL et al (2004) Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry 9(7):684–697, 643

    Article  CAS  PubMed  Google Scholar 

  5. Sun G, Wang J, Zhang J, Ma C, Shao C, Hao J et al (2014) High-resolution magic angle spinning (1)H magnetic resonance spectroscopy detects choline as a biomarker in a swine obstructive chronic pancreatitis model at an early stage. Mol BioSyst 10(3):467–474

    Article  CAS  PubMed  Google Scholar 

  6. Andrew ER, Bradbury A, Eades RG (1958) Nuclear magnetic resonance spectra from a crystal rotated at high speed. Nature 182:1659

    Article  CAS  Google Scholar 

  7. Hashim F, Denis C-M, Ronald S, Wolfgang B, William MK, André JS (2013) HR-MAS NMR spectroscopy: a practical guide for natural samples. Curr Org Chem 17(24):3013–3031

    Article  CAS  Google Scholar 

  8. Ramadhar TR, Amador F, Ditty MJT, Power WP (2008) Inverse H-C ex situ HRMAS NMR experiments for solid-phase peptide synthesis. Magn Reson Chem 46(1):30–35

    Article  CAS  PubMed  Google Scholar 

  9. Bharti S, Sinha N, Shankar Joshi B, Kumar Mandal S, Roy R, Khetrapal CL (2008) Improved quantification from 1H-NMR spectra using reduced repetition times. Metabolomics 4:367–376

    Article  CAS  Google Scholar 

  10. Savorani F, Tomasi G, Engelsen SB (2010) Icoshift: a versatile tool for the rapid alignment of 1D NMR spectra. J Magn Reson 202(2):190–202

    Article  CAS  PubMed  Google Scholar 

  11. Nielsen N-PV, Carstensen JM, Smedsgaard J (1998) Aligning of single and multiple wavelength chromatographic profiles for chemometric data analysis using correlation optimised warping. J Chromatogr A 805(1):17–35

    Article  CAS  Google Scholar 

  12. Giskeødegård GF, Bloemberg TG, Postma G, Sitter B, Tessem M-B, Gribbestad IS et al (2010) Alignment of high resolution magic angle spinning magnetic resonance spectra using warping methods. Anal Chim Acta 683(1):1–11

    Article  PubMed  CAS  Google Scholar 

  13. Dieterle F, Ross A, Schlotterbeck G, Senn H (2006) Probabilistic quotient normalization as robust method to account for dilution of complex biological mixtures. Application in 1H NMR metabonomics. Anal Chem 78(13):4281–4290

    Article  CAS  PubMed  Google Scholar 

  14. Wishart DS, Jewison T, Guo AC, Wilson M, Knox C, Liu Y et al (2013) HMDB 3.0--the human Metabolome database in 2013. Nucleic Acids Res 41(Database issue):D801–D807

    CAS  PubMed  Google Scholar 

  15. Giskeodegard GF, Bertilsson H, Selnaes KM, Wright AJ, Bathen TF, Viset T et al (2013) Spermine and citrate as metabolic biomarkers for assessing prostate cancer aggressiveness. PLoS One 8(4):e62375

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Heinzer-Schweizer S, De Zanche N, Pavan M, Mens G, Sturzenegger U, Henning A et al (2010) In-vivo assessment of tissue metabolite levels using 1H MRS and the electric REference to access in vivo concentrations (ERETIC) method. NMR Biomed 23(4):406–413

    CAS  PubMed  Google Scholar 

  17. Wider G, Dreier L (2006) Measuring protein concentrations by NMR spectroscopy. J Am Chem Soc 128(8):2571–2576

    Article  CAS  PubMed  Google Scholar 

  18. Wright AJ, Fellows GA, Griffiths JR, Wilson M, Bell BA, Howe FA (2010) Ex-vivo HRMAS of adult brain tumours: metabolite quantification and assignment of tumour biomarkers. Mol Cancer 9:66

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Hao J, Astle W, De Iorio M, Ebbels TMD (2012) BATMAN—an R package for the automated quantification of metabolites from nuclear magnetic resonance spectra using a Bayesian model. Bioinformatics 28(15):2088–2090

    Article  CAS  PubMed  Google Scholar 

  20. Euceda LR, Haukaas TH, Bathen TF, Giskeodegard GF (2018) Prediction of clinical endpoints in breast cancer using NMR metabolic profiles. Methods Mol Biol 1711:167–189

    Article  CAS  PubMed  Google Scholar 

  21. Westerhuis JA, Hoefsloot HCJ, Smit S, Vis DJ, Smilde AK, van Velzen EJJ et al (2008) Assessment of PLSDA cross validation. Metabolomics 4(1):81–89

    Article  CAS  Google Scholar 

  22. Giskeodegard GF, Cao MD, Bathen TF (2015) High-resolution magic-angle-spinning NMR spectroscopy of intact tissue. Methods Mol Biol 1277:37–50

    Article  PubMed  CAS  Google Scholar 

  23. Findeisen M, Brand T, Berger S (2006) A 1H-NMR thermometer suitable for cryoprobes. Magn Reson Chem 45(2):175–178

    Article  CAS  Google Scholar 

  24. Piotto M, Elbayed K, Wieruszeski JM, Lippens G (2005) Practical aspects of shimming a high resolution magic angle spinning probe. J Magn Reson 173(1):84–89

    Article  CAS  PubMed  Google Scholar 

  25. De Meyer T, Sinnaeve D, Van Gasse B, Tsiporkova E, Rietzschel ER, De Buyzere ML et al (2008) NMR-based characterization of metabolic alterations in hypertension using an adaptive, intelligent binning algorithm. Anal Chem 80(10):3783–3790

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Circulation and Medical Imaging, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

    Maria T. Grinde, Guro F. Giskeødegård, Trygve Andreassen, May-Britt Tessem, Tone F. Bathen & Siver A. Moestue

Authors
  1. Maria T. Grinde
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  2. Guro F. Giskeødegård
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  3. Trygve Andreassen
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  4. May-Britt Tessem
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  5. Tone F. Bathen
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  6. Siver A. Moestue
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Corresponding author

Correspondence to Tone F. Bathen .

Editor information

Editors and Affiliations

  1. Northwest Metabolomics Research Center, Mitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA, USA

    G. A. Nagana Gowda

  2. Northwest Metabolomics Research Center, Mitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington, Fred Hutch Cancer Research Center, Seattle, WA, USA

    Daniel Raftery

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Grinde, M.T., Giskeødegård, G.F., Andreassen, T., Tessem, MB., Bathen, T.F., Moestue, S.A. (2019). Biomarker Discovery Using NMR-Based Metabolomics of Tissue. In: Gowda, G., Raftery, D. (eds) NMR-Based Metabolomics. Methods in Molecular Biology, vol 2037. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9690-2_15

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  • DOI: https://doi.org/10.1007/978-1-4939-9690-2_15

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9689-6

  • Online ISBN: 978-1-4939-9690-2

  • eBook Packages: Springer Protocols

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