%0 Journal Article %A Li, Mujia Jenny %A Meyer, Larissa Chiara %A Meier, Nadine %A Witte, Jannik %A Maldacker, Maximilian %A Seredynska, Adrianna %A Schueler, Julia %A Schilling, Oliver %A Föll, Melanie Christine %T Spatial Proteomics by Parallel Accumulation-Serial Fragmentation Supported MALDI MS/MS Imaging: A First Glance Into Multiplexed and Spatial Peptide Identification. %J Rapid communications in mass spectrometry %V 39 %N 9 %@ 0951-4198 %C New York, NY %I Wiley Interscience %M DKFZ-2025-00301 %P e10006 %D 2025 %X In spatial proteomics, matrix-assisted laser desorption/ionization (MALDI) imaging enables rapid and cost-effective peptide measurements. Yet, in situ peptide identification remains challenging. Therefore, this study aims to integrate the trapped ion mobility spectrometry (TIMS)-based parallel accumulation-serial fragmentation (PASEF) into MALDI imaging of tryptic peptides to enable multiplexed MS/MS imaging.An initial MALDI TIMS MS1 survey measurement was performed, followed by a manual generation of a precursor list containing mass over charge values and ion mobility windows. Inside the dual TIMS system, submitted precursors were trapped, separately eluted by their ion mobility and analyzed in a quadrupole time-of-flight device, thereby enabling multiplexed MALDI MS/MS imaging. Finally, precursors were identified by peptide to spectrum matching.This study presents the first multiplexed MALDI TIMS MS/MS imaging (iprm-PASEF) of tryptic peptides. Its applicability was showcased on two histomorphologically distinct tissue specimens in a four-plex and five-plex setup. Precursors were successfully identified by the search engine MASCOT in one single MALDI imaging experiment for each respective tissue. Peptide identifications were corroborated by liquid-chromatography tandem mass spectrometry experiments and fragment colocalization analyses.In this study, we present a novel pipeline, based on iprm-PASEF, that allows the multiplexed and spatial identification of tryptic peptides in MALDI imaging. Hence, it marks a first step towards the integration of MALDI imaging into the emerging field of spatial proteomics. %K Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization: methods %K Proteomics: methods %K Tandem Mass Spectrometry: methods %K Animals %K Peptides: chemistry %K Peptides: analysis %K Ion Mobility Spectrometry: methods %K Peptide Fragments: analysis %K Peptide Fragments: chemistry %K MALDI imaging (Other) %K MS/MS imaging (Other) %K TIMS (Other) %K iprm‐PASEF (Other) %K peptide imaging (Other) %K spatial proteomics (Other) %K Peptides (NLM Chemicals) %K Peptide Fragments (NLM Chemicals) %F PUB:(DE-HGF)16 %9 Journal Article %$ pmid:39910729 %R 10.1002/rcm.10006 %U https://inrepo02.dkfz.de/record/298584