Skip to main content

Experimental and Study Design Considerations for Uncovering Oncometabolites

  • Protocol
  • First Online:
Cancer Gene Networks

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1513))

Abstract

Metabolomics as a field has gained attention due to its potential for biomarker discovery, namely because it directly reflects disease phenotype and is the downstream effect of posttranslational modifications. The field provides a “top-down,” integrated view of biochemistry in complex organisms, as opposed to the traditional “bottom-up” approach that aims to analyze networks of interactions between genes, proteins and metabolites. It also allows for the detection of thousands of endogenous metabolites in various clinical biospecimens in a high-throughput manner, including tissue and biofluids such as blood and urine. Of note, because biological fluid samples can be collected relatively easily, the time-dependent fluctuations of metabolites can be readily studied in detail.

In this chapter, we aim to provide an overview of (1) analytical methods that are currently employed in the field, and (2) study design concepts that should be considered prior to conducting high-throughput metabolomics studies. While widely applicable, the concepts presented here are namely applicable to high-throughput untargeted studies that aim to search for metabolite biomarkers that are associated with a particular human disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Dunn WB, Broadhurst DI, Atherton HJ et al (2011) Systems level studies of mammalian metabolomes: the roles of mass spectrometry and nuclear magnetic resonance spectroscopy. Chem Soc Rev 40:387–426

    Article  CAS  PubMed  Google Scholar 

  2. van der Greef J, Stroobant P, van der Heijden R (2004) The role of analytical sciences in medical systems biology. Curr Opin Chem Biol 8:559–565

    Article  PubMed  Google Scholar 

  3. Stepien M, Duarte-Salles T, Fedirko V et al (2016) Alteration of amino acid and biogenic amine metabolism in hepatobiliary cancers: findings from a prospective cohort study. Int J Can 138:348–360

    Article  CAS  Google Scholar 

  4. Dang L, White DW, Gross S et al (2010) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 465:966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ward PS, Patel J, Wise DR et al (2010) The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate. Cancer Cell 17:225–234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Pollard PJ, Briere JJ, Alam NA et al (2005) Accumulation of Krebs cycle intermediates and over-expression of HIF1alpha in tumours which result from germline FH and SDH mutations. Hum Mol Genet 14:2231–2239

    Article  CAS  PubMed  Google Scholar 

  7. Robaglia A, Cau P, Bottini J, Seite R (1989) Effects of isolation and high helium pressure on the nucleolus of sympathetic neurons in the rat superior cervical ganglion. J Auton Neurosci 27:207–219

    CAS  Google Scholar 

  8. Yin P, Peter A, Franken H et al (2013) Preanalytical aspects and sample quality assessment in metabolomics studies of human blood. Clin Chem 59:833–845

    Article  CAS  PubMed  Google Scholar 

  9. Libiseller G, Dvorzak M, Kleb U et al (2015) IPO: a tool for automated optimization of XCMS parameters. BMC Bioinformatics 16:118

    Article  PubMed  PubMed Central  Google Scholar 

  10. Clasquin MF, Melamud E, Rabinowitz JD (2012) LC-MS data processing with MAVEN: a metabolomic analysis and visualization engine. Curr Protoc Bioinform. Chapter 14:Unit14. 11. doi:10.1002/0471250953.bi1411s37.

  11. Smith CA, O'Maille G, Want EJ et al (2005) METLIN: a metabolite mass spectral database. Ther Drug Monit 27:747–751

    Article  CAS  PubMed  Google Scholar 

  12. Wishart DS, Jewison T, Guo AC et al (2013) HMDB 3.0—the human metabolome database in 2013. Nucleic Acids Res 41:D801–D807

    Article  CAS  PubMed  Google Scholar 

  13. Skogerson K, Wohlgemuth G, Barupal DK, Fiehn O (2011) The volatile compound BinBase mass spectral database. BMC Bioinformatics 12:321

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Haug K, Salek RM, Conesa P et al (2013) MetaboLights—an open-access general-purpose repository for metabolomics studies and associated meta-data. Nucleic Acids Res 41:D781–D786

    Article  CAS  PubMed  Google Scholar 

  15. Beynon RJ, Pratt JM (2005) Metabolic labeling of proteins for proteomics. Mol Cell Proteomics 4:857–872

    Article  CAS  PubMed  Google Scholar 

  16. Rousseaux M, Petit H, Hache JC et al (1985) Ocular and head movements in infarctions of the thalamic region. Rev Neurol 141:391–403

    CAS  PubMed  Google Scholar 

  17. Fung ET, Enderwick C (2002) ProteinChip clinical proteomics: computational challenges and solutions. Biotechniques Suppl:34–38, 40–41

    PubMed  Google Scholar 

  18. Warrack BM, Hnatyshyn S, Ott KH et al (2009) Normalization strategies for metabonomic analysis of urine samples. J Chromatogr B Analyt Technol Biomed Life Sci 877:547–552

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Ewy A. Mathé .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media New York

About this protocol

Cite this protocol

Haznadar, M., Mathé, E.A. (2017). Experimental and Study Design Considerations for Uncovering Oncometabolites. In: Kasid, U., Clarke, R. (eds) Cancer Gene Networks. Methods in Molecular Biology, vol 1513. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6539-7_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-6539-7_4

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6537-3

  • Online ISBN: 978-1-4939-6539-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics