Analytical Methods for Mass Spectrometry-Based Metabolomics Studies
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Abstract
The advancement of mass spectrometry-based analytical platform largely facilitates small-molecule metabolomics studies, which allows simultaneously analysis of a large number of metabolites from bio-samples and give a general picture of metabolic changes related to diseases or environmental alteration. Due to the large diversity of cellular metabolites, globally and precisely examining metabolic profile remains the most challenging part in metabolomic experiment. Mass spectrometry coupled with liquid chromatography enhances sensitivity and resolving power of metabolites identification and quantification, as well as versatility of analyzing a wide array of metabolites. In this chapter, we discussed the technical aspects of each step in the workflow of metabolomics studies we aimed to give technical guidelines for metabolomics investigation design and approach.
Keywords
Metabolomics Liquid chromatography-mass spectrometry HILIC Ion pairing chromatography Polar metabolites Glycolysis Tricarboxylic acids cycle Pentose phosphate pathwayReferences
- 1.Nielsen, J. (2003). It is all about metabolic fluxes. Journal of Bacteriology, 185(24), 7031–7035.PubMedPubMedCentralGoogle Scholar
- 2.Villas-Bôas, S. G., Mas, S., Åkesson, M., Smedsgaard, J., & Nielsen, J. (2005). Mass spectrometry in metabolome analysis. Mass Spectrometry Reviews, 24(5), 613–646.PubMedGoogle Scholar
- 3.Gibney, M. J., Walsh, M., Brennan, L., Roche, H. M., German, B., & Van Ommen, B. (2005). Metabolomics in human nutrition: Opportunities and challenges. The American Journal of Clinical Nutrition, 82(3), 497–503.PubMedGoogle Scholar
- 4.Armitage, E. G., & Barbas, C. (2014). Metabolomics in cancer biomarker discovery: Current trends and future perspectives. Journal of Pharmaceutical and Biomedical Analysis, 87, 1–11.PubMedGoogle Scholar
- 5.Brown, D. G., Rao, S., Weir, T. L., O’Malia, J., Bazan, M., Brown, R. J., et al. (2016). Metabolomics and metabolic pathway networks from human colorectal cancers, adjacent mucosa, and stool. Cancer & Metabolism, 4(1), 11.Google Scholar
- 6.Wang, Z., Klipfell, E., Bennett, B. J., Koeth, R., Levison, B. S., DuGar, B., et al. (2011). Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature, 472(7341), 57.PubMedPubMedCentralGoogle Scholar
- 7.Wang, Z., Tang, W. W., Buffa, J. A., Fu, X., Britt, E. B., Koeth, R. A., et al. (2014). Prognostic value of choline and betaine depends on intestinal microbiota-generated metabolite trimethylamine-N-oxide. European Heart Journal, 35(14), 904–910.PubMedPubMedCentralGoogle Scholar
- 8.Warrier, M., Shih, D. M., Burrows, A. C., Ferguson, D., Gromovsky, A. D., Brown, A. L., et al. (2015). The TMAO-generating enzyme flavin monooxygenase 3 is a central regulator of cholesterol balance. Cell Reports, 10(3), 326–338.PubMedPubMedCentralGoogle Scholar
- 9.Gregory, J. C., Buffa, J. A., Org, E., Wang, Z., Levison, B. S., Zhu, W., et al. (2015). Transmission of atherosclerosis susceptibility with gut microbial transplantation. The Journal of Biological Chemistry, 290(9), 5647–5660.PubMedGoogle Scholar
- 10.Ward, P. S., Patel, J., Wise, D. R., Abdel-Wahab, O., Bennett, B. D., Coller, H. A., et al. (2010). The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting α-ketoglutarate to 2-hydroxyglutarate. Cancer Cell, 17(3), 225–234.PubMedPubMedCentralGoogle Scholar
- 11.Yang, M., Soga, T., & Pollard, P. J. (2013). Oncometabolites: Linking altered metabolism with cancer. The Journal of Clinical Investigation, 123(9), 3652–3658.PubMedPubMedCentralGoogle Scholar
- 12.Xia, J., Broadhurst, D. I., Wilson, M., & Wishart, D. S. (2013). Translational biomarker discovery in clinical metabolomics: An introductory tutorial. Metabolomics, 9(2), 280–299.PubMedGoogle Scholar
- 13.Stewart, N. A., Buch, S. C., Conrads, T. P., & Branch, R. A. (2011). A UPLC-MS/MS assay of the “Pittsburgh cocktail”: Six CYP probe-drug/metabolites from human plasma and urine using stable isotope dilution. Analyst, 136(3), 605–612.PubMedGoogle Scholar
- 14.Zhu, H., Bogdanov, M. B., Boyle, S. H., Matson, W., Sharma, S., Matson, S., et al. (2013). Pharmacometabolomics of response to sertraline and to placebo in major depressive disorder–possible role for methoxyindole pathway. PLoS One, 8(7), e68283.PubMedPubMedCentralGoogle Scholar
- 15.Ellero-Simatos, S., Lewis, J., Georgiades, A., Yerges-Armstrong, L., Beitelshees, A., Horenstein, R., et al. (2014). Pharmacometabolomics reveals that serotonin is implicated in aspirin response variability. CPT: Pharmacometrics & Systems Pharmacology, 3(7), 1–9.Google Scholar
- 16.Villas-Bôas, S. G. (2007). Sampling and sample preparation. In Metabolome analysis: An introduction (pp. 39–82). NJ: John Wiley & Sons.Google Scholar
- 17.Mushtaq, M. Y., Choi, Y. H., Verpoorte, R., & Wilson, E. G. (2014). Extraction for metabolomics: Access to the metabolome. Phytochemical Analysis: PCA, 25(4), 291–306.PubMedGoogle Scholar
- 18.Liu, X., Sadhukhan, S., Sun, S., Wagner, G. R., Hirschey, M. D., Qi, L., et al. (2015). High-resolution metabolomics with acyl-CoA profiling reveals widespread remodeling in response to diet. Molecular & Cellular Proteomics: MCP, 14(6), 1489–1500.PubMedGoogle Scholar
- 19.Fan, J., Ye, J., Kamphorst, J. J., Shlomi, T., Thompson, C. B., & Rabinowitz, J. D. (2014). Quantitative flux analysis reveals folate-dependent NADPH production. Nature, 510(7504), 298.PubMedPubMedCentralGoogle Scholar
- 20.Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., et al. (2008). Global metabolic profiling of Escherichia coli cultures: An evaluation of methods for quenching and extraction of intracellular metabolites. Analytical Chemistry, 80(8), 2939–2948.PubMedGoogle Scholar
- 21.Want, E. J., Masson, P., Michopoulos, F., Wilson, I. D., Theodoridis, G., Plumb, R. S., et al. (2013). Global metabolic profiling of animal and human tissues via UPLC-MS. Nature Protocols, 8(1), 17.PubMedGoogle Scholar
- 22.Theobald, U., Mailinger, W., Reuss, M., & Rizzi, M. (1993). In vivo analysis of glucose-induced fast changes in yeast adenine nucleotide pool applying a rapid sampling technique. Analytical Biochemistry, 214(1), 31–37.PubMedGoogle Scholar
- 23.Villas-Bôas, S. G., Højer-Pedersen, J., Åkesson, M., Smedsgaard, J., & Nielsen, J. (2005). Global metabolite analysis of yeast: Evaluation of sample preparation methods. Yeast, 22(14), 1155–1169.PubMedGoogle Scholar
- 24.Jang, C., Chen, L., & Rabinowitz, J. D. (2018). Metabolomics and isotope tracing. Cell, 173(4), 822–837.PubMedPubMedCentralGoogle Scholar
- 25.Wittmann, C., Krömer, J. O., Kiefer, P., Binz, T., & Heinzle, E. (2004). Impact of the cold shock phenomenon on quantification of intracellular metabolites in bacteria. Analytical Biochemistry, 327(1), 135–139.PubMedGoogle Scholar
- 26.Beltran, A., Suarez, M., Rodriguez, M. A., Vinaixa, M., Samino, S., Arola, L., et al. (2012). Assessment of compatibility between extraction methods for NMR- and LC/MS-based metabolomics. Analytical Chemistry, 84(14), 5838–5844.PubMedGoogle Scholar
- 27.Geier, F. M., Want, E. J., Leroi, A. M., & Bundy, J. G. (2011). Cross-platform comparison of Caenorhabditis elegans tissue extraction strategies for comprehensive metabolome coverage. Analytical Chemistry, 83(10), 3730–3736.PubMedGoogle Scholar
- 28.Shestov, A. A., Lee, S. C., Nath, K., Guo, L., Nelson, D. S., Roman, J. C., et al. (2016). (13)C MRS and LC-MS flux analysis of tumor intermediary metabolism. Frontiers in Oncology, 6, 135.PubMedPubMedCentralGoogle Scholar
- 29.Bedi Jr., K. C., Snyder, N. W., Brandimarto, J., Aziz, M., Mesaros, C., Worth, A. J., et al. (2016). Evidence for intramyocardial disruption of lipid metabolism and increased myocardial ketone utilization in advanced human heart failure. Circulation, 133(8), 706–716.PubMedPubMedCentralGoogle Scholar
- 30.Samuelson, O., & Sjostrom, E. (1952). Utilization of ion exchangers in analytical chemistry. XXIV. Isolation of monosaccharides. Svensk Kemisk Tidskrift, 64, 305–314.Google Scholar
- 31.Alpert, A. J. (1990). Hydrophilic-interaction chromatography for the separation of peptides, nucleic acids and other polar compounds. Journal of Chromatography, 499, 177–196.PubMedGoogle Scholar
- 32.Tang, D. Q., Zou, L., Yin, X. X., & Ong, C. N. (2016). HILIC-MS for metabolomics: An attractive and complementary approach to RPLC-MS. Mass Spectrometry Reviews, 35(5), 574–600.PubMedGoogle Scholar
- 33.Hemström, P., & Irgum, K. (2006). Hydrophilic interaction chromatography. Journal of Separation Science, 29(12), 1784–1821.PubMedGoogle Scholar
- 34.Alpert, A. J., Shukla, M., Shukla, A. K., Zieske, L. R., Yuen, S. W., Ferguson, M. A., et al. (1994). Hydrophilic-interaction chromatography of complex carbohydrates. Journal of Chromatography, 676(1), 191–202.PubMedGoogle Scholar
- 35.Jandera, P., Hájek, T., Škeříková, V., & Soukup, J. (2010). Dual hydrophilic interaction-RP retention mechanism on polar columns: Structural correlations and implementation for 2-D separations on a single column. Journal of Separation Science, 33(6–7), 841–852.PubMedGoogle Scholar
- 36.McCalley, D. V. (2010). Study of the selectivity, retention mechanisms and performance of alternative silica-based stationary phases for separation of ionised solutes in hydrophilic interaction chromatography. Journal of Chromatography, 1217(20), 3408–3417.PubMedGoogle Scholar
- 37.Cubbon, S., Antonio, C., Wilson, J., & Thomas-Oates, J. (2010). Metabolomic applications of HILIC–LC–MS. Mass Spectrometry Reviews, 29(5), 671–684.PubMedGoogle Scholar
- 38.Gama, M. R., da Costa Silva, R. G., Collins, C. H., & Bottoli, C. B. (2012). Hydrophilic interaction chromatography. TrAC Trends in Analytical Chemistry, 37, 48–60.Google Scholar
- 39.Guo, Y., & Gaiki, S. (2005). Retention behavior of small polar compounds on polar stationary phases in hydrophilic interaction chromatography. Journal of Chromatography, 1074(1–2), 71–80.PubMedGoogle Scholar
- 40.Buszewski, B., & Noga, S. (2012). Hydrophilic interaction liquid chromatography (HILIC)—A powerful separation technique. Analytical and Bioanalytical Chemistry, 402(1), 231–247.PubMedGoogle Scholar
- 41.Bajad, S. U., Lu, W., Kimball, E. H., Yuan, J., Peterson, C., & Rabinowitz, J. D. (2006). Separation and quantitation of water soluble cellular metabolites by hydrophilic interaction chromatography-tandem mass spectrometry. Journal of Chromatography, 1125(1), 76–88.PubMedGoogle Scholar
- 42.Cubbon, S., Bradbury, T., Wilson, J., & Thomas-Oates, J. (2007). Hydrophilic interaction chromatography for mass spectrometric metabonomic studies of urine. Analytical Chemistry, 79(23), 8911–8918.PubMedGoogle Scholar
- 43.Zhang, X., Rauch, A., Lee, H., Xiao, H., Rainer, G., & Logothetis, N. K. (2007). Capillary hydrophilic interaction chromatography/mass spectrometry for simultaneous determination of multiple neurotransmitters in primate cerebral cortex. Rapid Communications in Mass Spectrometry: An International Journal Devoted to the Rapid Dissemination of Up-to-the-Minute Research in Mass Spectrometry, 21(22), 3621–3628.Google Scholar
- 44.Zauner, G., Deelder, A. M., & Wuhrer, M. (2011). Recent advances in hydrophilic interaction liquid chromatography (HILIC) for structural glycomics. Electrophoresis, 32(24), 3456–3466.PubMedGoogle Scholar
- 45.Gika, H. G., Theodoridis, G. A., Vrhovsek, U., & Mattivi, F. (2012). Quantitative profiling of polar primary metabolites using hydrophilic interaction ultrahigh performance liquid chromatography–tandem mass spectrometry. Journal of Chromatography, 1259, 121–127.PubMedGoogle Scholar
- 46.Paek, I. B., Moon, Y., Ji, H. Y., Kim, H.-H., Lee, H. W., Lee, Y.-B., et al. (2004). Hydrophilic interaction liquid chromatography–tandem mass spectrometry for the determination of levosulpiride in human plasma. Journal of Chromatography B, 809(2), 345–350.Google Scholar
- 47.Liu, X., Ser, Z., Cluntun, A. A., Mentch, S. J., & Locasale, J. W. (2014). A strategy for sensitive, large scale quantitative metabolomics. Journal of Visualized Experiments: JoVE, (87). https://doi.org/10.3791/51358
- 48.Liu, X., Ser, Z., & Locasale, J. W. (2014). Development and quantitative evaluation of a high-resolution metabolomics technology. Analytical Chemistry, 86(4), 2175–2184.PubMedPubMedCentralGoogle Scholar
- 49.Hopfgartner, G., Varesio, E., Tschäppät, V., Grivet, C., Bourgogne, E., & Leuthold, L. A. (2004). Triple quadrupole linear ion trap mass spectrometer for the analysis of small molecules and macromolecules. Journal of Mass Spectrometry, 39(8), 845–855.PubMedGoogle Scholar
- 50.Contrepois, K., Jiang, L., & Snyder, M. (2015). Optimized analytical procedures for the untargeted metabolomic profiling of human urine and plasma by combining hydrophilic interaction and reverse-phase liquid chromatography-mass spectrometry. Molecular Cell Proteomics, 14, 1684–1695.Google Scholar
- 51.Guo, Y., & Gaiki, S. (2011). Retention and selectivity of stationary phases for hydrophilic interaction chromatography. Journal of Chromatography, 1218(35), 5920–5938.PubMedGoogle Scholar
- 52.Jandera, P. (2011). Stationary and mobile phases in hydrophilic interaction chromatography: A review. Analytica Chimica Acta, 692(1–2), 1–25.PubMedGoogle Scholar
- 53.Cecchi, T. (2011). Retention mechanism for ion-pair chromatography with chaotropic reagents. From ion-pair chromatography toward a unified salt chromatography. Advances in Chromatography, 49, 1–35.PubMedGoogle Scholar
- 54.Lu, W., Clasquin, M. F., Melamud, E., Amador-Noguez, D., Caudy, A. A., & Rabinowitz, J. D. (2010). Metabolomic analysis via reversed-phase ion-pairing liquid chromatography coupled to a stand alone orbitrap mass spectrometer. Analytical Chemistry, 82(8), 3212–3221.PubMedPubMedCentralGoogle Scholar
- 55.Gong, L., & McCullagh, J. S. (2014). Comparing ion-pairing reagents and sample dissolution solvents for ion-pairing reversed-phase liquid chromatography/electrospray ionization mass spectrometry analysis of oligonucleotides. Rapid Communications in Mass Spectrometry: RCM, 28(4), 339–350.PubMedGoogle Scholar
- 56.Guo, L., Worth, A. J., Mesaros, C., Snyder, N. W., Glickson, J. D., & Blair, I. A. (2016). Diisopropylethylamine/hexafluoroisopropanol-mediated ion-pairing ultra-high-performance liquid chromatography/mass spectrometry for phosphate and carboxylate metabolite analysis: Utility for studying cellular metabolism. Rapid Communications in Mass Spectrometry: RCM, 30(16), 1835–1845.PubMedGoogle Scholar
- 57.Apffel, A., Chakel, J. A., Fischer, S., Lichtenwalter, K., & Hancock, W. S. (1997). Analysis of oligonucleotides by HPLC-electrospray ionization mass spectrometry. Analytical Chemistry, 69(7), 1320–1325.PubMedGoogle Scholar
- 58.Frederick, D. W., Trefely, S., Buas, A., Goodspeed, J., Singh, J., Mesaros, C., et al. (2017). Stable isotope labeling by essential nutrients in cell culture (SILEC) for accurate measurement of nicotinamide adenine dinucleotide metabolism. The Analyst, 142(23), 4431–4437.PubMedPubMedCentralGoogle Scholar
- 59.Basu, S. S., Mesaros, C., Gelhaus, S. L., & Blair, I. A. (2011). Stable isotope labeling by essential nutrients in cell culture for preparation of labeled coenzyme A and its thioesters. Analytical Chemistry, 83(4), 1363–1369.PubMedPubMedCentralGoogle Scholar
- 60.Guo, L., Shestov, A. A., Worth, A. J., Nath, K., Nelson, D. S., Leeper, D. B., et al. (2016). Inhibition of mitochondrial complex II by the anticancer agent lonidamine. The Journal of Biological Chemistry, 291(1), 42–57.PubMedGoogle Scholar
- 61.Tolstikov, V. V., & Fiehn, O. (2002). Analysis of highly polar compounds of plant origin: Combination of hydrophilic interaction chromatography and electrospray ion trap mass spectrometry. Analytical Biochemistry, 301(2), 298–307.PubMedGoogle Scholar
- 62.Moco, S., Vervoort, J., Bino, R. J., De Vos, R. C., & Bino, R. (2007). Metabolomics technologies and metabolite identification. TrAC Trends in Analytical Chemistry, 26(9), 855–866.Google Scholar
- 63.Liu, X., & Locasale, J. W. (2017). Metabolomics: A primer. Trends in Biochemical Sciences, 42(4), 274–284.PubMedPubMedCentralGoogle Scholar
- 64.D’Atri, V., Causon, T., Hernandez-Alba, O., Mutabazi, A., Veuthey, J. L., Cianferani, S., et al. (2018). Adding a new separation dimension to MS and LC–MS: What is the utility of ion mobility spectrometry? Journal of Separation Science, 41(1), 20–67.PubMedGoogle Scholar
- 65.Smith, C. A., O’Maille, G., Want, E. J., Qin, C., Trauger, S. A., Brandon, T. R., et al. (2005). METLIN: A metabolite mass spectral database. Therapeutic Drug Monitoring, 27(6), 747–751.PubMedGoogle Scholar
- 66.Wishart, D. S., Jewison, T., Guo, A. C., Wilson, M., Knox, C., Liu, Y., et al. (2012). HMDB 3.0—The human metabolome database in 2013. Nucleic Acids Research, 41(D1), D801–D807.PubMedPubMedCentralGoogle Scholar
- 67.Kanehisa, M., Goto, S., Sato, Y., Kawashima, M., Furumichi, M., & Tanabe, M. (2013). Data, information, knowledge and principle: Back to metabolism in KEGG. Nucleic Acids Research, 42(D1), D199–D205.PubMedPubMedCentralGoogle Scholar
- 68.Horai, H., Arita, M., Kanaya, S., Nihei, Y., Ikeda, T., Suwa, K., et al. (2010). MassBank: A public repository for sharing mass spectral data for life sciences. Journal of Mass Spectrometry, 45(7), 703–714.PubMedGoogle Scholar
- 69.Kind, T., & Fiehn, O. (2007). Seven golden rules for heuristic filtering of molecular formulas obtained by accurate mass spectrometry. BMC Bioinformatics, 8(1), 105.PubMedPubMedCentralGoogle Scholar
- 70.Tachibana, C. (2014). What’s next in’omics: The metabolome. Science, 345(6203), 1519–1521.Google Scholar
- 71.Wolf, S., Schmidt, S., Müller-Hannemann, M., & Neumann, S. (2010). In silico fragmentation for computer assisted identification of metabolite mass spectra. BMC Bioinformatics, 11(1), 148.PubMedPubMedCentralGoogle Scholar
- 72.Kind, T., Wohlgemuth, G., Lee, D. Y., Lu, Y., Palazoglu, M., Shahbaz, S., et al. (2009). FiehnLib: Mass spectral and retention index libraries for metabolomics based on quadrupole and time-of-flight gas chromatography/mass spectrometry. Analytical Chemistry, 81(24), 10038–10048.PubMedPubMedCentralGoogle Scholar
- 73.Saccenti, E., Hoefsloot, H. C., Smilde, A. K., Westerhuis, J. A., & Hendriks, M. M. (2014). Reflections on univariate and multivariate analysis of metabolomics data. Metabolomics, 10(3), 361–374.Google Scholar
- 74.Keun, H. C., Ebbels, T. M., Bollard, M. E., Beckonert, O., Antti, H., Holmes, E., et al. (2004). Geometric trajectory analysis of metabolic responses to toxicity can define treatment specific profiles. Chemical Research in Toxicology, 17(5), 579–587.PubMedGoogle Scholar
- 75.Morrison, D. F. (2005). Multivariate analysis of variance. In Encyclopedia of biostatistics (5th ed.). NJ: John Wiley & Sons.Google Scholar
- 76.Ellis, D. I., & Goodacre, R. (2006). Metabolic fingerprinting in disease diagnosis: Biomedical applications of infrared and Raman spectroscopy. Analyst, 131(8), 875–885.PubMedGoogle Scholar
- 77.Shlens, J. (2005). A tutorial on principal component analysis. La Jolla: Systems Neurobiology Laboratory, Salk Insitute for Biological Studies.Google Scholar
- 78.Xie, L. W., Atanasov, A. G., Guo, D. A., Malainer, C., Zhang, J. X., Zehl, M., et al. (2014). Activity-guided isolation of NF-kappaB inhibitors and PPARgamma agonists from the root bark of Lycium chinense Miller. Journal of Ethnopharmacology, 152(3), 470–477.PubMedGoogle Scholar
- 79.Nyamundanda, G., Brennan, L., & Gormley, I. C. (2010). Probabilistic principal component analysis for metabolomic data. BMC Bioinformatics, 11(1), 571.PubMedPubMedCentralGoogle Scholar
- 80.Pan, Z., Gu, H., Talaty, N., Chen, H., Shanaiah, N., Hainline, B. E., et al. (2007). Principal component analysis of urine metabolites detected by NMR and DESI–MS in patients with inborn errors of metabolism. Analytical and Bioanalytical Chemistry, 387(2), 539–549.PubMedGoogle Scholar
- 81.Gu, H., Pan, Z., Xi, B., Asiago, V., Musselman, B., & Raftery, D. (2011). Principal component directed partial least squares analysis for combining nuclear magnetic resonance and mass spectrometry data in metabolomics: Application to the detection of breast cancer. Analytica Chimica Acta, 686(1–2), 57–63.PubMedGoogle Scholar
- 82.Wold, S., Sjöström, M., & Eriksson, L. (2001). PLS-regression: A basic tool of chemometrics. Chemometrics and Intelligent Laboratory Systems, 58(2), 109–130.Google Scholar
- 83.Boulesteix, A.-L., & Strimmer, K. (2006). Partial least squares: A versatile tool for the analysis of high-dimensional genomic data. Briefings in Bioinformatics, 8(1), 32–44.PubMedGoogle Scholar
- 84.Fonville, J. M., Richards, S. E., Barton, R. H., Boulange, C. L., Ebbels, T. M., Nicholson, J. K., et al. (2010). The evolution of partial least squares models and related chemometric approaches in metabonomics and metabolic phenotyping. Journal of Chemometrics, 24(11–12), 636–649.Google Scholar
- 85.Mehmood, T., Martens, H., Sæbø, S., Warringer, J., & Snipen, L. (2011). A partial least squares based algorithm for parsimonious variable selection. Algorithms for Molecular Biology, 6(1), 27.PubMedGoogle Scholar
- 86.Mehmood, T., Liland, K. H., Snipen, L., & Sæbø, S. (2012). A review of variable selection methods in partial least squares regression. Chemometrics and Intelligent Laboratory Systems, 118, 62–69.Google Scholar
- 87.Xi, B., Gu, H., Baniasadi, H., & Raftery, D. (2014). Statistical analysis and modeling of mass spectrometry-based metabolomics data. In Mass spectrometry in metabolomics (pp. 333–353). New York: Springer.Google Scholar
- 88.Gromski, P. S., Muhamadali, H., Ellis, D. I., Xu, Y., Correa, E., Turner, M. L., et al. (2015). A tutorial review: Metabolomics and partial least squares-discriminant analysis—a marriage of convenience or a shotgun wedding. Analytica Chimica Acta, 879, 10–23.PubMedGoogle Scholar