Identification of MALDI imaging proteolytic peptides using LC-MS/MS-based biomarker discovery data: a proof of concept

Purpose Identification of proteolytic peptides from matrix-assisted laser desorption/ionization (MALDI) imaging remains a challenge. The low fragmentation yields obtained using in situ post source decay impairs identification. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an alternati...

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Hauptverfasser: Longuespée, Rémi (VerfasserIn) , Kazdal, Daniel (VerfasserIn) , Zgorzelski, Christiane (VerfasserIn) , Kriegsmann, Katharina (VerfasserIn) , Schirmacher, Peter (VerfasserIn) , Fresnais, Margaux (VerfasserIn) , Oliveira, Cristiano (VerfasserIn) , Kriegsmann, Mark (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: January 2019
In: Proteomics. Clinical applications
Year: 2018, Jahrgang: 13, Heft: 1
ISSN:1862-8354
DOI:10.1002/prca.201800158
Online-Zugang:Verlag, Volltext: https://doi.org/10.1002/prca.201800158
Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/prca.201800158
Volltext
Verfasserangaben:Rémi Longuespée, Alice Ly, Rita Casadonte, Kristina Schwamborn, Daniel Kazdal, Christiane Zgorzelski, Christine Bollwein, Katharina Kriegsmann, Wilko Weichert, Jörg Kriegsmann, Peter Schirmacher, Margaux Fresnais, Cristiano Oliveira, Mark Kriegsmann
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Zusammenfassung:Purpose Identification of proteolytic peptides from matrix-assisted laser desorption/ionization (MALDI) imaging remains a challenge. The low fragmentation yields obtained using in situ post source decay impairs identification. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an alternative to in situ MS/MS, but leads to multiple identification candidates for a given mass. The authors propose to use LC-MS/MS-based biomarker discovery results to reliably identify proteolytic peptides from MALDI imaging. Experimental design The authors defined m/z values of interest for high grade squamous intraepithelial lesion (HSIL) by MALDI imaging. In parallel the authors used data from a biomarker discovery study to correlate m/z from MALDI imaging with masses of peptides identified by LC-MS/MS in HSIL. The authors neglected candidates that were not significantly more abundant in HSIL according to the biomarker discovery investigation. Results The authors assigned identifications to three m/z of interest. The number of possible identifiers for MALDI imaging m/z peaks using LC-MS/MS-based biomarker discovery studies was reduced by about tenfold compared using a single LC-MS/MS experiment. One peptide identification candidate was validated by immunohistochemistry. Conclusion and clinical relevance This concept combines LC-MS/MS-based quantitative proteomics with MALDI imaging and allows reliable peptide identification. Public datasets from LC-MS/MS biomarker discovery experiments will be useful to identify MALDI imaging m/z peaks.
Beschreibung:First published: 07 December 2018
Gesehen am 08.07.2019
Beschreibung:Online Resource
ISSN:1862-8354
DOI:10.1002/prca.201800158