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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
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
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
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
Dang L, White DW, Gross S et al (2010) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 465:966
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
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
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
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
Libiseller G, Dvorzak M, Kleb U et al (2015) IPO: a tool for automated optimization of XCMS parameters. BMC Bioinformatics 16:118
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.
Smith CA, O'Maille G, Want EJ et al (2005) METLIN: a metabolite mass spectral database. Ther Drug Monit 27:747–751
Wishart DS, Jewison T, Guo AC et al (2013) HMDB 3.0—the human metabolome database in 2013. Nucleic Acids Res 41:D801–D807
Skogerson K, Wohlgemuth G, Barupal DK, Fiehn O (2011) The volatile compound BinBase mass spectral database. BMC Bioinformatics 12:321
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
Beynon RJ, Pratt JM (2005) Metabolic labeling of proteins for proteomics. Mol Cell Proteomics 4:857–872
Rousseaux M, Petit H, Hache JC et al (1985) Ocular and head movements in infarctions of the thalamic region. Rev Neurol 141:391–403
Fung ET, Enderwick C (2002) ProteinChip clinical proteomics: computational challenges and solutions. Biotechniques Suppl:34–38, 40–41
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
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights 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