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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 | Source: | RAPID COMMUNICATIONS IN MASS SPECTROMETRY, 31(17), p. 1396-1404 | 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. | Document URI: | http://hdl.handle.net/1942/24418 | ISSN: | 0951-4198 | e-ISSN: | 1097-0231 | DOI: | 10.1002/rcm.7910 | ISI #: | 000406934900003 | Rights: | Copyright © 2017 John Wiley & Sons, Ltd. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2018 |
Appears in Collections: | Research publications |
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