title: Annotation of metabolites from gas chromatography/atmospheric pressure chemical ionization tandem mass spectrometry data using an in silico generated compound database and MetFrag.
abstract: BACKGROUND
  Gas chromatography (GC) coupled to atmospheric pressure chemical ionization quadrupole time-of-flight mass spectrometry (APCI-QTOFMS) is an emerging technology in metabolomics. Reference spectra for GC/APCI-MS/MS barely exist; therefore, in silico fragmentation approaches and structure databases are prerequisites for annotation. To expand the limited coverage of derivatised structures in structure databases, in silico derivatisation procedures are required.
  
  
  METHODS
  A cheminformatics workflow has been developed for in silico derivatisation of compounds found in KEGG and PubChem, and validated on the Golm Metabolome Database (GMD). To demonstrate this workflow, these in silico generated databases were applied together with MetFrag to APCI-MS/MS spectra acquired from GC/APCI-MS/MS profiles of Arabidopsis thaliana and Solanum tuberosum. The Metabolite-Likeness of the original candidate structure was included as additional scoring term aiming at candidate structures of natural origin.
  
  
  RESULTS
  The validation of our in silico derivatisation workflow on the GMD showed a true positive rate of 94%. MetFrag was applied to two datasets. In silico derivatisation of the KEGG and PubChem database served as a candidate source. For both datasets the Metabolite-Likeness score improved the identification performance. The derivatised data sources have been included into the MetFrag web application for the annotation of GC/APCI-MS/MS spectra.
  
  
  CONCLUSIONS
  We demonstrated that MetFrag can support the identification of components from GC/APCI-MS/MS profiles, especially in the (common) case where reference spectra are not available. This workflow can be easily adapted to other types of derivatisation and is freely accessible together with the generated structure databases.
authors.affiliation: Leibniz Institute of Plant Biochemistry, Department of Stress and Developmental Biology, Weinberg 3, 06120, Halle (Saale), Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Ruttkies
authors.affiliation: Leibniz Institute of Plant Biochemistry, Department of Stress and Developmental Biology, Weinberg 3, 06120, Halle (Saale), Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Strehmel
authors.affiliation: Leibniz Institute of Plant Biochemistry, Department of Stress and Developmental Biology, Weinberg 3, 06120, Halle (Saale), Germany.
authors.forename: Dierk
authors.initials: D
authors.lastname: Scheel
authors.affiliation: Leibniz Institute of Plant Biochemistry, Department of Stress and Developmental Biology, Weinberg 3, 06120, Halle (Saale), Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Neumann
mesh_terms: D003198:Computer Simulation; D066289:Data Curation / Q000379:methods*; D062126:Databases, Chemical; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D020407:Internet; D008956:Models, Chemical; D010936:Plant Extracts / Q000032:analysis / Q000737:chemistry; D015203:Reproducibility of Results; D012984:Software; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D010936:Plant Extracts