title: A statistical procedure to selectively detect metabolite signals in LC-MS data based on using variable isotope ratios.
abstract: The tracing of metabolite signals in LC-MS data using stable isotope-labeled compounds has been described in the literature. However, the filtering efficiency and confidence when mining metabolite signals in complex LC-MS datasets can be improved. Here, we propose an additional statistical procedure to increase the compound-derived signal mining efficiency. This method also provides a highly confident approach to screen out metabolite signals because the correlation of varying concentration ratios of native/stable isotope-labeled compounds and their instrumental response ratio is used. An in-house computational program [signal mining algorithm with isotope tracing (SMAIT)] was developed to perform the statistical procedure. To illustrate the SMAIT concept and its effectiveness for mining metabolite signals in LC-MS data, the plasticizer, di-(2-ethylhexyl) phthalate (DEHP), was used as an example. The statistical procedure effectively filtered 15 probable metabolite signals from 3617 peaks in the LC-MS data. These probable metabolite signals were considered structurally related to DEHP. Results obtained here suggest that the statistical procedure could be used to confidently facilitate the detection of probable metabolites from a compound-derived precursor presented in a complex LC-MS dataset.
authors.affiliation: Department of Environmental and Occupational Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Lung-Cheng
authors.initials: LC
authors.lastname: Lin
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Wu
authors.forename: Vincent Shin-Mu
authors.initials: VS
authors.lastname: Tseng
authors.forename: Lien-Chin
authors.initials: LC
authors.lastname: Chen
authors.forename: Yu-Chen
authors.initials: YC
authors.lastname: Chang
authors.forename: Pao-Chi
authors.initials: PC
authors.lastname: Liao
mesh_terms: D000465:Algorithms; D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D019295:Computational Biology / Q000379:methods*; D004051:Diethylhexyl Phthalate / Q000737:chemistry; D007554:Isotopes / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D015233:Models, Statistical; D051381:Rats; D017208:Rats, Wistar; D052616:Solid Phase Extraction
chemical_list: D007554:Isotopes; D004051:Diethylhexyl Phthalate