title: Extending the Dynamic Range in Metabolomics Experiments by Automatic Correction of Peaks Exceeding the Detection Limit.
abstract: Metabolomics, the analysis of potentially all small molecules within a biological system, has become a valuable tool for biomarker identification and the elucidation of biological processes. While metabolites are often present in complex mixtures at extremely different concentrations, the dynamic range of available analytical methods to capture this variance is generally limited. Here, we show that gas chromatography coupled to atmospheric pressure chemical ionization mass spectrometry (GC-APCI-MS), a state of the art analytical technology applied in metabolomics analyses, shows an average linear range (LR) of 2.39 orders of magnitude for a set of 62 metabolites from a representative compound mixture. We further developed a computational tool to extend this dynamic range on average by more than 1 order of magnitude, demonstrated with a dilution series of the compound mixture, using robust and automatic reconstruction of intensity values exceeding the detection limit. The tool is freely available as an R package (CorrectOverloadedPeaks) from CRAN ( https://cran.r-project.org/ ) and can be incorporated in a metabolomics data processing pipeline facilitating large screening assays.
authors.affiliation: Charité-Universitätsmedizin Berlin , Molekulares Krebsforschungszentrum (MKFZ), Augustenburger Platz 1, 13353 Berlin, Germany.|German Cancer Consortium, Deutsches Krebsforschungzentrum (DKFZ) , Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Lisec
authors.affiliation: Charité-Universitätsmedizin Berlin , Molekulares Krebsforschungszentrum (MKFZ), Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Hoffmann
authors.affiliation: Charité-Universitätsmedizin Berlin , Molekulares Krebsforschungszentrum (MKFZ), Augustenburger Platz 1, 13353 Berlin, Germany.|Max-Delbrück-Center for Molecular Medicine (MDC) , Robert-Rössle-Straße 10, 13125 Berlin, Germany.|Berlin Institute of Health (BIH) , Kapelle-Ufer 2, 10117 Berlin, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Schmitt
authors.affiliation: Charité-Universitätsmedizin Berlin , Molekulares Krebsforschungszentrum (MKFZ), Augustenburger Platz 1, 13353 Berlin, Germany.|Berlin Institute of Health (BIH) , Kapelle-Ufer 2, 10117 Berlin, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Jaeger
mesh_terms: D000465:Algorithms; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D057230:Limit of Detection; D055432:Metabolomics / Q000379:methods*