MassIVE MSV000099481

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In Situ, Antibody-Independent, and Multiplexed Characterization of Amyloid Plaques by MALDI MS/MS Imaging Using iprm-PASEF

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Description

Amyloidosis collectively describes a heterogeneous group of protein aggregation-based diseases involving the misfolding and extracellular accumulation of fibril-forming amyloid proteins. Diagnosing amyloidosis is difficult due to its many subtypes (e.g. AA, AL, ATTR), with varying symptoms. Current diagnosis often involves Congo red staining, but it has limitations in quantification and specificity. A novel method called iprm-PASEF exploits MALDI imaging and offers a faster, spatially resolved, antibody-independent technique for identifying peptides while preserving tissue structure. In this study, iprm-PASEF was used to further evaluate its applicability on amyloidosis. FFPE slides of an amyloidosis TMA including biopsies of 18 amyloidosis positive tissues were prepared for tryptic peptide MALDI imaging. An initial MALDI TIMS MS1 measurement was performed, followed by the manual generation of a precursor list containing mass-to-charge ratios and ion mobility windows. In a second iprm-PASEF measurement, the selected precursors are analyzed in a multiplexed MALDI MS/MS mode. Peptide identification was achieved through peptide-to-spectrum matching using MASCOT. Within the course of this study, we characterized an amyloidosis TMA consisting of AA, AL and ATTR amyloidosis diseased tissue with MALDI imaging of tryptic peptides. We successfully identified eight amyloidosis related peptides derived from serum amyloid A, vitronectin, apolipoprotein E, serum amyloid P component and transthyretin receptor in one single iprm-PASEF measurement. Peptide signals mapped to amyloidogenic plaques determined in a Congo red staining. Some of these peptides were specifically found in ATTR and AA amyloidosis. This represents a significant step towards integrating MALDI imaging into the diagnostic process for amyloidosis. All Datasets are uploaded separateley. This file contains the dataset for amyloidosis MS1 data. [doi:10.25345/C5SJ1B45W] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: MALDI imaging ; TIMS ; peptides ; iprm-PASEF ; MALDI TIMS MS/MS Imaging ; spatial Proteomics ; Amyloidosis ; DatasetType:Proteomics

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Principal Investigators:
(in alphabetical order) 		Prof. Dr. Oliver Schilling, Medical Center - University of Freiburg, Germany
Submitting User: oliver_schilling
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