title: Combining NMR and LC/MS Using Backward Variable Elimination: Metabolomics Analysis of Colorectal Cancer, Polyps, and Healthy Controls.
abstract: Both nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) play important roles in metabolomics. The complementary features of NMR and MS make their combination very attractive; however, currently the vast majority of metabolomics studies use either NMR or MS separately, and variable selection that combines NMR and MS for biomarker identification and statistical modeling is still not well developed. In this study focused on methodology, we developed a backward variable elimination partial least-squares discriminant analysis algorithm embedded with Monte Carlo cross validation (MCCV-BVE-PLSDA), to combine NMR and targeted liquid chromatography (LC)/MS data. Using the metabolomics analysis of serum for the detection of colorectal cancer (CRC) and polyps as an example, we demonstrate that variable selection is vitally important in combining NMR and MS data. The combined approach was better than using NMR or LC/MS data alone in providing significantly improved predictive accuracy in all the pairwise comparisons among CRC, polyps, and healthy controls. Using this approach, we selected a subset of metabolites responsible for the improved separation for each pairwise comparison, and we achieved a comprehensive profile of altered metabolite levels, including those in glycolysis, the TCA cycle, amino acid metabolism, and other pathways that were related to CRC and polyps. MCCV-BVE-PLSDA is straightforward, easy to implement, and highly useful for studying the contribution of each individual variable to multivariate statistical models. On the basis of these results, we recommend using an appropriate variable selection step, such as MCCV-BVE-PLSDA, when analyzing data from multiple analytical platforms to obtain improved statistical performance and a more accurate biological interpretation, especially for biomarker discovery. Importantly, the approach described here is relatively universal and can be easily expanded for combination with other analytical technologies.
authors.affiliation: Department of Information Engineering, East China University of Technology , 418 Guanglan Avenue, Nanchang, Jiangxi Province 330013, China.|Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington , 850 Republican Street, Seattle, Washington 98109, United States.
authors.forename: Lingli
authors.initials: L
authors.lastname: Deng
authors.affiliation: Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington , 850 Republican Street, Seattle, Washington 98109, United States.|Jiangxi Key Laboratory for Mass Spectrometry and Instrumentation, East China University of Technology , 418 Guanglan Avenue, Nanchang, Jiangxi Province 330013, China.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Gu
authors.affiliation: Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington , 850 Republican Street, Seattle, Washington 98109, United States.
authors.forename: Jiangjiang
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington , 850 Republican Street, Seattle, Washington 98109, United States.
authors.forename: G A
authors.initials: GA
authors.lastname: Nagana Gowda
authors.affiliation: Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington , 850 Republican Street, Seattle, Washington 98109, United States.
authors.forename: Danijel
authors.initials: D
authors.lastname: Djukovic
authors.affiliation: Department of Medicine, University of Washington , 825 Eastlake Avenue East, Seattle, Washington 98109, United States.|Indiana University Melvin and Bren Simon Cancer Center , 535 Barnhill Drive, Indianapolis, Indiana 46202, United States.
authors.forename: E Gabriela
authors.initials: EG
authors.lastname: Chiorean
authors.affiliation: Northwest Metabolomics Research Center, Department of Anesthesiology and Pain Medicine, University of Washington , 850 Republican Street, Seattle, Washington 98109, United States.|Department of Chemistry, Purdue University , 560 Oval Drive, West Lafayette, Indiana 47907, United States.|Public Health Sciences Division, Fred Hutchinson Cancer Research Center , 1100 Fairview Avenue North, Seattle, Washington 98109, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Raftery
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D002853:Chromatography, Liquid; D015179:Colorectal Neoplasms / Q000175:diagnosis*; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D008297:Male; D013058:Mass Spectrometry; D055432:Metabolomics; D008875:Middle Aged; D009010:Monte Carlo Method; D019906:Nuclear Magnetic Resonance, Biomolecular; D011127:Polyps / Q000175:diagnosis*; D055815:Young Adult