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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/24418

Title: InSourcerer: a high-throughput method to search for unknown metabolite modifications by mass spectrometry
Authors: Mrzic, Aida
Lermyte, Frederik
Vu, Trung Nghia
Valkenborg, Dirk
Laukens, Kris
Issue Date: 2017
Publisher: WILEY
Abstract: Rationale: Using mass spectrometry, the analysis of known metabolite structures has become feasible in a systematic high-throughput fashion. Nevertheless, the identification of previously unknown structures remains challenging, partially because many unidentified variants originate from known molecules that underwent unexpected modifications. Here, we present a method for the discovery of unknown metabolite modifications and conjugate metabolite isoforms in a high-throughput fashion. Methods: The method is based on user-controlled in-source fragmentation which is used to induce loss of weakly bound modifications. This is followed by the comparison of product ions from in-source fragmentation and collision-induced dissociation (CID). Diagonal MS2-MS3 matching allows the detection of unknown metabolite modifications, as well as substructure similarities. As the method relies heavily on the advantages of in-source fragmentation and its ability to 'magically' elucidate unknown modification, we have named it inSourcerer as a portmanteau of in-source and sorcerer. Results: The method was evaluated using a set of 15 different cytokinin standards. Product ions from in-source fragmentation and CID were compared. Hierarchical clustering revealed that good matches are due to the presence of common substructures. Plant leaf extract, spiked with a mix of all 15 standards, was used to demonstrate the method's ability to detect these standards in a complex mixture, as well as confidently identify compounds already present in the plant material. Conclusions: Here we present a method that incorporates a classic liquid chromatography/mass spectrometry (LC/MS) workflow with fragmentation models and computational algorithms. The assumptions upon which the concept of the method was built were shown to be valid and the method showed that in-source fragmentation can be used to pinpoint structural similarities and indicate the occurrence of a modification.
Notes: [Lermyte, Frederik; Valkenborg, Dirk] Flemish Inst Technol Res VITO, Appl Bio & Mol Syst, Mol, Belgium. [Lermyte, Frederik; Valkenborg, Dirk] Univ Antwerp, UA VITO Ctr Prote, Antwerp, Belgium. [Valkenborg, Dirk] Hasselt Univ, Interuniv Inst Biostat & Stat Bioinformat, Hasselt, Belgium. [Lermyte, Frederik] Univ Antwerp, Dept Chem, Antwerp, Belgium. [Mrzic, Aida; Trung Nghia Vu; Laukens, Kris] Univ Antwerp, Dept Math & Comp Sci, Antwerp, Belgium. [Mrzic, Aida; Trung Nghia Vu; Laukens, Kris] Univ Antwerp, Antwerp Univ Hosp, Biomed Informat Res Network Antwerpen Biomina, Antwerp, Belgium.
URI: http://hdl.handle.net/1942/24418
DOI: 10.1002/rcm.7910
ISI #: 000406934900003
ISSN: 0951-4198
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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