Multiplexed Tandem Mass Spectrometry Imaging Enables Large-Scale Isomer Mapping and Annotation in Tissues.
Overview
- Department of Chemistry for Life Science, Uppsala University, Uppsala, Sweden
- Center of Excellence for the Chemical Mechanisms of Life, Uppsala University, Uppsala, Sweden
- Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Location VU Medical Center, Amsterdam, the Netherlands
- Amsterdam Neuroscience, Amsterdam UMC, Amsterdam, the Netherlands
- MS Center Amsterdam, Amsterdam UMC, Location VU Medical Center, Amsterdam, the Netherlands
- Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam UMC, Amsterdam, the Netherlands
Abstract
Accurate molecular annotation is essential for deciphering biochemical processes in spatial biology. Here, we present a scalable and broadly applicable molecular annotation tool for tandem mass spectrometry imaging (MS2I). Our workflow includes parallel image acquisition (PIA) for parallel MS2I and an open‐access computational framework for spatial similarity networking (SSN) that enables molecular annotation of MS2I data with isomeric specificity. The PIA enables simultaneous untargeted MSI and targeted MS2I ensuring structure‐specific imaging of hundreds of molecules in a single experiment. The SSN increases annotation confidence through graph‐based spatial correlation of product ion distributions, opening up new avenues for data investigation and annotation from both MSI and MS2I data. By integrating PIA and SSN into a single workflow, we visualize and annotate 134 phospholipid isomers and isobars in mouse brain tissue. Furthermore, we demonstrate the biological utility of the platform by mapping cholesterol metabolism in human multiple sclerosis brain tissue, revealing lesion‐associated cholesterol oxidation pathways. Finally, we propose annotation confidence levels for structural annotation in MSI. Overall, PIA and SSN together provide large‐scale, structure‐specific MSI, expanding the scope for spatial metabolomics, lipidomics, and chemical pathology through molecular annotation beyond current capabilities.
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Code
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LanekoffLab
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Code Availability Statement
The source code and the compiled version of the software are available at https://
Reproduced under the paper's license (CC BY), from the paper cited above.
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Data Availability Statement
Data presented in the manuscript are available from the corresponding author upon reasonable request.
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Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 6 authors, 5 keywords, 8 MeSH terms, 4 funders, 53 references.
Cite
This paper
Sharma, V. V., Toth, G., Martinis, R., Hansen, C. E., Kooij, G., & Lanekoff, I. (2026). Multiplexed Tandem Mass Spectrometry Imaging Enables Large-Scale Isomer Mapping and Annotation in Tissues. Angewandte Chemie (International ed. in English), 65(20), e22119. https://
BibTeX
@article{sharma2026multi
author = {Sharma, Varun V and Toth, Gabor and Martinis, Robert and Hansen, Cathrin E and Kooij, Gijs and Lanekoff, Ingela},
title = {{Multiplexed Tandem Mass Spectrometry Imaging Enables Large-Scale Isomer Mapping and Annotation in Tissues}},
journal = {Angewandte Chemie (International ed. in English)},
year = {2026},
month = mar,
volume = {65},
number = {20},
pages = {e22119},
publisher = {Wiley},
issn = {1433-7851},
doi = {10.1002/
url = {https://
pmid = {41913395},
pmcid = {PMC13159427}
}
RIS
TY - JOUR
AU - Sharma, Varun V
AU - Toth, Gabor
AU - Martinis, Robert
AU - Hansen, Cathrin E
AU - Kooij, Gijs
AU - Lanekoff, Ingela
TI - Multiplexed Tandem Mass Spectrometry Imaging Enables Large-Scale Isomer Mapping and Annotation in Tissues
T2 - Angewandte Chemie (International ed. in English)
J2 - Angew Chem Int Ed Engl
PY - 2026
DA - 2026/
VL - 65
IS - 20
SP - e22119
SN - 1433-7851
PB - Wiley
DO - 10.1002/
UR - https://
LA - en
ER -
CSL-JSON
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