Closed-Loop, Multiobjective Optimization of Two-Dimensional Gas Chromatography/Mass Spectrometry for Serum Metabolomics

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• 作者：Steve O' Hagan ; Warwick B. Dunn ; Joshua D. Knowles ; David Broadhurst ; Rebecca Williams ; Jason J. Ashworth ; Maureen Cameron ; Douglas B. Kell
• 刊名：Analytical Chemistry
• 出版年：2007
• 出版时间：January 15, 2007
• 年：2007
• 卷：79
• 期：2
• 页码：464 - 476
• 全文大小：928K
• 年卷期：v.79,no.2(January 15, 2007)
• ISSN：1520-6882

文摘

Metabolomics seeks to measure potentially all the metabolites in a biological sample, and consequently, weneed to develop and optimize methods to increase significantly the number of metabolites we can detect. Weextended the closed-loop (iterative, automated) optimization system that we had previously developed for one-dimensional GC-TOF-MS (O'Hagan, S.; Dunn, W. B.;Brown, M.; Knowles, J. D.; Kell, D. B. Anal. Chem.2005, 77, 290-303) to comprehensive two-dimensional(GC×GC) chromatography. The heuristic approach usedwas a multiobjective version of the efficient global optimization algorithm. In just 300 automated runs, weimproved the number of metabolites observable relativeto those in 1D GC by some 3-fold. The optimized conditions allowed for the detection of over 4000 raw peaks,of which some 1800 were considered to be real metabolitepeaks and not impurities or peaks with a signal/noiseratio of less than 5. A variety of computational methodsserved to explain the basis for the improvement. Thisclosed-loop optimization strategy is a generic and powerfulapproach for the optimization of any analytical instrumentation.