Abstract
The technical advances in mass spectrometry, particularly the development of (ultra)-high-resolution/mass accuracy measurement capabilities in combination with refinement of soft ionization techniques, have increased the application and success of lipidomics to answer biological questions in relation to lipid metabolism. Together with other omics technologies, lipidomics has become an important tool to practice systems biology as lipids comprise a very significant part of the metabolome and play pleiotropic roles in cellular functions. As an increasing number of disorders are linked to lipid metabolism, lipidomics is used to search for biomarkers, understand disease mechanism and follow the efficacy of therapeutic options. This review provides a first introduction to the major methodological strategies currently used for mass spectrometry-based lipidomics and associated data pre-processing and analysis.
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Abbreviations
- ANOVA:
-
Analysis of variance
- APCI:
-
Atmospheric pressure chemical ionization
- (D)FBA (Dynamic):
-
flux-balance analysis
- ESI:
-
Electrospray ionization
- FDR:
-
False discovery rate
- FWHM:
-
Full width at half maximum
- GSEA:
-
Gene set enrichment analysis
- LC:
-
Liquid chromatography
- MALDI:
-
Matrix-assisted laser desorption/ionization
- MDMS:
-
Multi-dimensional MS
- MSEA:
-
Metabolite set enrichment analysis
- MRM:
-
Multiple reaction monitoring
- PCA:
-
Principal component analysis
- PLS-DA:
-
Partial-least-squares discriminant analysis
- (U)HPLC:
-
(Ultra)-high performance chromatography
- Q:
-
Quadrupole
- QC:
-
Quality control
- QqQ:
-
Triple quadrupole instrument
- TOF:
-
Time-of-flight
References
Abbott SK, Jenner AM, Mitchell TW, Brown SH, Halliday GM, Garner B (2013) An improved high-throughput lipid extraction method for the analysis of human brain lipids. Lipids 48:307–318
Barupal DK, Haldiya PK, Wohlgemuth G et al (2012) MetaMapp: mapping and visualizing metabolomic data by integrating information from biochemical pathways and chemical and mass spectral similarity. BMC Bioinforma 13:99
Berry KA, Hankin JA, Barkley RM, Spraggins JM, Caprioli RM, Murphy RC (2011) MALDI imaging of lipid biochemistry in tissues by mass spectrometry. Chem Rev 111:6491–6512
Bhattacharya SK (2013) Recent advances in shotgun lipidomics and their implication for vision research and ophthalmology. Curr Eye Res 38:417–427
Bligh EG, Dyer WJ (1959) A rapid method of total lipid extraction and purification. Can J Biochem Physiol 37:911–917
Boccard J, Veuthey JL, Rudaz S (2010) Knowledge discovery in metabolomics: an overview of MS data handling. J Sep Sci 33:290–304
Box GEP, Hunter JS, Hunter WG (2005) Statistics for experimenters: design, innovation, and discovery.: Wiley, New York
Brugger B (2014) Lipidomics: analysis of the lipid composition of cells and subcellular organelles by electrospray ionization mass spectrometry. Annu Rev Biochem 83:79–98
Byrdwell WC (2001) Atmospheric pressure chemical ionization mass spectrometry for analysis of lipids. Lipids 36:327–346
Chadeau-Hyam M, Campanella G, Jombart T et al (2013) Deciphering the complex: methodological overview of statistical models to derive OMICS-based biomarkers. Environ Mol Mutagen 54:542–557
Ellis SR, Brown SH, In Het Panhuis M, Blanksby SJ, Mitchell TW (2013) Surface analysis of lipids by mass spectrometry: more than just imaging. Prog Lipid Res 52:329–353
Fahy E, Subramaniam S, Murphy RC et al (2009) Update of the LIPID MAPS comprehensive classification system for lipids. J Lipid Res 50(Suppl):S9–14
Folch J, Lees M, Sloane Stanley GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226:497–509
Fuchs B, Suss R, Schiller J (2010) An update of MALDI-TOF mass spectrometry in lipid research. Prog Lipid Res 49:450–475
Han X, Yang K, Gross RW (2012) Multi-dimensional mass spectrometry-based shotgun lipidomics and novel strategies for lipidomic analyses. Mass Spectrom Rev 31:134–178
Hendriks MMWB, Eeuwijk FA, Jellema RH et al (2011) Data-processing strategies for metabolomics studies. TrAC Trends Anal Chem 30:1685–1698
Herzog R, Schuhmann K, Schwudke D et al (2012) LipidXplorer: a software for consensual cross-platform lipidomics. PLoS ONE 7:e29851
Hyotylainen T, Oresic M (2014) Systems biology strategies to study lipidomes in health and disease. Prog Lipid Res 55C:43–60
Jung HR, Sylvanne T, Koistinen KM, Tarasov K, Kauhanen D, Ekroos K (2011) High throughput quantitative molecular lipidomics. Biochim Biophys Acta 1811:925–934
Karnovsky A, Weymouth T, Hull T et al (2012) Metscape 2 bioinformatics tool for the analysis and visualization of metabolomics and gene expression data. Bioinformatics 28:373–380
Kind T, Liu KH, Lee do Y, DeFelice B, Meissen JK, Fiehn O (2013) LipidBlast in silico tandem mass spectrometry database for lipid identification. Nat Methods 10:755–758
Knittelfelder OL, Weberhofer BP, Eichmann TO, Kohlwein SD, Rechberger GN (2014) A versatile ultra-high performance LC-MS method for lipid profiling. J Chromatogr B: Analyt Technol Biomed Life Sci 951–952:119–128
Kotze HL, Armitage EG, Sharkey KJ et al (2013) A novel untargeted metabolomics correlation-based network analysis incorporating human metabolic reconstructions. BMC Syst Biol 7:107
Li M, Yang L, Bai Y, Liu H (2014) Analytical methods in lipidomics and their applications. Anal Chem 86:161–175
Liu ZY (2012) An introduction to hybrid ion trap/time-of-flight mass spectrometry coupled with liquid chromatography applied to drug metabolism studies. J Mass Spectrom 47:1627–1642
Mahadevan R, Edwards JS, Doyle FJ 3rd (2002) Dynamic flux balance analysis of diauxic growth in Escherichia coli. Biophys J 83:1331–1340
Matyash V, Liebisch G, Kurzchalia TV, Shevchenko A, Schwudke D (2008) Lipid extraction by methyl-tert-butyl ether for high-throughput lipidomics. J Lipid Res 49:1137–1146
Mueller D, Heinzle E (2013) Stable isotope-assisted metabolomics to detect metabolic flux changes in mammalian cell cultures. Curr Opin Biotechnol 24:54–59
Nielsen J (2003) It is all about metabolic fluxes. J Bacteriol 185:7031–7035
Oresic M (2011) Informatics and computational strategies for the study of lipids. Biochim Biophys Acta 1811:991–999
Orth JD, Thiele I, Palsson BO (2010) What is flux balance analysis? Nat Biotechnol 28:245–248
Peskov K, Mogilevskaya E, Demin O (2012) Kinetic modelling of central carbon metabolism in Escherichia coli. FEBS J 279:3374–3385
Reis A, Rudnitskaya A, Blackburn GJ, Mohd Fauzi N, Pitt AR, Spickett CM (2013) A comparison of five lipid extraction solvent systems for lipidomic studies of human LDL. J Lipid Res 54:1812–1824
Saccenti E, Hoefsloot HJ, Smilde A, Westerhuis J, Hendriks MWB (2014) Reflections on univariate and multivariate analysis of metabolomics data. Metabolomics 10:361–374
Salek RM, Haug K, Steinbeck C (2013) Dissemination of metabolomics results: role of MetaboLights and COSMOS. Gigascience 2:8
Sreenivasaiah PK, Rani S, Cayetano J, Arul N, Kim do H (2012) IPAVS: integrated pathway resources, analysis and visualization system. Nucleic Acids Res 40:D803–808
Theodoridis GA, Gika HG, Want EJ, Wilson ID (2012) Liquid chromatography-mass spectrometry based global metabolite profiling: a review. Anal Chim Acta 711:7–16
Want E, Masson P (2011) Processing and analysis of GC/LC-MS-based metabolomics data. Methods Mol Biol 708:277–298
Wolf C, Quinn PJ (2008) Lipidomics: practical aspects and applications. Prog Lipid Res 47:15–36
Xia J, Wishart DS (2011) Web-based inference of biological patterns, functions and pathways from metabolomic data using MetaboAnalyst. Nat Protoc 6:743–760
Acknowledgments
We thank Willem Kulik for critical reading of the manuscript and Henk van Lenthe for technical assistance.
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This article does not contain any studies with human or animal subjects performed by any of the authors.
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Communicated by: Matthias Baumgartner
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Vaz, F.M., Pras-Raves, M., Bootsma, A.H. et al. Principles and practice of lipidomics. J Inherit Metab Dis 38, 41–52 (2015). https://doi.org/10.1007/s10545-014-9792-6
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DOI: https://doi.org/10.1007/s10545-014-9792-6