Premium
Identification of MALDI Imaging Proteolytic Peptides Using LC‐MS/MS‐Based Biomarker Discovery Data: A Proof of Concept
Author(s) -
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
Publication year - 2019
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.201800158
Subject(s) - biomarker discovery , biomarker , maldi imaging , proteomics , mass spectrometry , mass spectrometry imaging , matrix assisted laser desorption/ionization , tandem mass spectrometry , chemistry , computational biology , chromatography , biology , biochemistry , organic chemistry , adsorption , desorption , gene
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.