Identification of MALDI Imaging Proteolytic Peptides Using LC‐MS/MS‐Based Biomarker Discovery Data: A Proof of Concept. Issue 1 (19th December 2018)

• Record Type: Journal Article
• Authors: Longuespée, Rémi; Ly, Alice; Casadonte, Rita; Schwamborn, Kristina; Kazdal, Daniel; Zgorzelski, Christiane; Bollwein, Christine; Kriegsmann, Katharina; Weichert, Wilko; Kriegsmann, Jörg; Schirmacher, Peter; Fresnais, Margaux; Oliveira, Cristiano; Kriegsmann, Mark
• Other Names: Longuespée Rémi guestEditor.; Casadonte Rita guestEditor.; Schwamborn Kristina guestEditor.; Kriegsmann Mark guestEditor.
• Is Part Of: Proteomics. Volume 13:Issue 1(2019)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-12-19
• Subjects: identification -- liquid chromatography tandem mass spectrometry -- matrix‐assisted laser desorption/ionization imaging -- microproteomics; Proteomics -- Periodicals; 572.605
• DOI: 10.1002/prca.201800158
• Languages: English
• ISSNs: 1862-8346

Abstract

Abstract : 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.