Mass Spectrometry Imaging for Spatially Resolved Multi-omics Molecular Mapping

Overview

Journal Npj Imaging

Date 2024 Jul 22

PMID 39036554

Authors

Hua Zhang

Kelly H Lu

Malik Ebbini

Penghsuan Huang

Haiyan Lu

Lingjun Li

Affiliations

Soon will be listed here.

Abstract

The recent upswing in the integration of spatial multi-omics for conducting multidimensional information measurements is opening a new chapter in biological research. Mapping the landscape of various biomolecules including metabolites, proteins, nucleic acids, etc., and even deciphering their functional interactions and pathways is believed to provide a more holistic and nuanced exploration of the molecular intricacies within living systems. Mass spectrometry imaging (MSI) stands as a forefront technique for spatially mapping the metabolome, lipidome, and proteome within diverse tissue and cell samples. In this review, we offer a systematic survey delineating different MSI techniques for spatially resolved multi-omics analysis, elucidating their principles, capabilities, and limitations. Particularly, we focus on the advancements in methodologies aimed at augmenting the molecular sensitivity and specificity of MSI; and depict the burgeoning integration of MSI-based spatial metabolomics, lipidomics, and proteomics, encompassing the synergy with other imaging modalities. Furthermore, we offer speculative insights into the potential trajectory of MSI technology in the future.

Citing Articles

Toward spatial glycomics and glycoproteomics: Innovations and applications.

Boottanun P, Fuseya S, Kuno A BBA Adv. 2025; 7:100146.

PMID: 40027887 PMC: 11869499. DOI: 10.1016/j.bbadva.2025.100146.

Spatial Proteomics by Parallel Accumulation-Serial Fragmentation Supported MALDI MS/MS Imaging: A First Glance Into Multiplexed and Spatial Peptide Identification.

Li M, Meyer L, Meier N, Witte J, Maldacker M, Seredynska A Rapid Commun Mass Spectrom. 2025; 39(9):e10006.

PMID: 39910729 PMC: 11799399. DOI: 10.1002/rcm.10006.

A Primer on Proteomic Characterization of Intercellular Communication in a Virus Microenvironment.

Kostas J, Brainard C, Cristea I Mol Cell Proteomics. 2025; 24(3):100913.

PMID: 39862905 PMC: 11889360. DOI: 10.1016/j.mcpro.2025.100913.

Proteomic Profiling Towards a Better Understanding of Genetic Based Muscular Diseases: The Current Picture and a Look to the Future.

Pauper M, Hentschel A, Tiburcy M, Beltran S, Ruck T, Schara-Schmidt U Biomolecules. 2025; 15(1).

PMID: 39858524 PMC: 11763865. DOI: 10.3390/biom15010130.

Mass Spectrometry Imaging Reveals Spatial Metabolic Alterations and Salidroside's Effects in Diabetic Encephalopathy.

Cheng S, Meng X, Wang Z, Lan T, Zhou Z, Wang Z Metabolites. 2024; 14(12).

PMID: 39728451 PMC: 11676703. DOI: 10.3390/metabo14120670.

References

Pareek V, Tian H, Winograd N, Benkovic S . Metabolomics and mass spectrometry imaging reveal channeled de novo purine synthesis in cells. Science. 2020; 368(6488):283-290. PMC: 7494208. DOI: 10.1126/science.aaz6465. View

Kuznetsov I, Filevich J, Dong F, Woolston M, Chao W, Anderson E . Three-dimensional nanoscale molecular imaging by extreme ultraviolet laser ablation mass spectrometry. Nat Commun. 2015; 6:6944. PMC: 4423227. DOI: 10.1038/ncomms7944. View

Lu H, Zhang H, Li L . Chemical tagging mass spectrometry: an approach for single-cell omics. Anal Bioanal Chem. 2023; 415(28):6901-6913. PMC: 10729908. DOI: 10.1007/s00216-023-04850-0. View

Kompauer M, Heiles S, Spengler B . Atmospheric pressure MALDI mass spectrometry imaging of tissues and cells at 1.4-μm lateral resolution. Nat Methods. 2016; 14(1):90-96. DOI: 10.1038/nmeth.4071. View

Jackson H, Fischer J, Zanotelli V, Ali H, Mechera R, Soysal S . The single-cell pathology landscape of breast cancer. Nature. 2020; 578(7796):615-620. DOI: 10.1038/s41586-019-1876-x. View

DelaCourt A, Liang H, Drake R, Angel P, Mehta A . Novel Combined Enzymatic Approach to Analyze Nonsialylated N-Linked Glycans through MALDI Imaging Mass Spectrometry. J Proteome Res. 2022; 21(8):1930-1938. DOI: 10.1021/acs.jproteome.2c00193. View

Kernalleguen A, Enjalbal C, Alvarez J, Belgacem O, Leonetti G, Lafitte D . Synthetic cannabinoid isomers characterization by MALDI-MS imaging: Application to single scalp hair. Anal Chim Acta. 2018; 1041:87-93. DOI: 10.1016/j.aca.2018.09.036. View

Zhang Y, Buchberger A, Muthuvel G, Li L . Expression and distribution of neuropeptides in the nervous system of the crab Carcinus maenas and their roles in environmental stress. Proteomics. 2015; 15(23-24):3969-79. PMC: 4921240. DOI: 10.1002/pmic.201500256. View

Zhang H, Shi X, Vu N, Li G, Li Z, Shi Y . On-Tissue Derivatization with Girard's Reagent P Enhances N-Glycan Signals for Formalin-Fixed Paraffin-Embedded Tissue Sections in MALDI Mass Spectrometry Imaging. Anal Chem. 2020; 92(19):13361-13368. PMC: 7544651. DOI: 10.1021/acs.analchem.0c02704. View

10.

Sun R, Tang W, Li P, Li B . Development of an Efficient On-Tissue Epoxidation Reaction Mediated by Urea Hydrogen Peroxide for MALDI MS/MS Imaging of Lipid C═C Location Isomers. Anal Chem. 2023; 95(43):16004-16012. DOI: 10.1021/acs.analchem.3c03262. View

11.

Tian H, Sheraz Nee Rabbani S, Vickerman J, Winograd N . Multiomics Imaging Using High-Energy Water Gas Cluster Ion Beam Secondary Ion Mass Spectrometry [(HO)-GCIB-SIMS] of Frozen-Hydrated Cells and Tissue. Anal Chem. 2021; 93(22):7808-7814. PMC: 8190772. DOI: 10.1021/acs.analchem.0c05210. View

12.

Sun C, Liu W, Geng Y, Wang X . On-Tissue Derivatization Strategy for Mass Spectrometry Imaging of Carboxyl-Containing Metabolites in Biological Tissues. Anal Chem. 2020; 92(18):12126-12131. DOI: 10.1021/acs.analchem.0c02303. View

13.

Swales J, Tucker J, Spreadborough M, Iverson S, Clench M, Webborn P . Mapping drug distribution in brain tissue using liquid extraction surface analysis mass spectrometry imaging. Anal Chem. 2015; 87(19):10146-52. DOI: 10.1021/acs.analchem.5b02998. View

14.

Balluff B, Heeren R, Race A . An overview of image registration for aligning mass spectrometry imaging with clinically relevant imaging modalities. J Mass Spectrom Adv Clin Lab. 2022; 23:26-38. PMC: 8821033. DOI: 10.1016/j.jmsacl.2021.12.006. View

15.

Zhang H, Delafield D, Li L . Mass spectrometry imaging: the rise of spatially resolved single-cell omics. Nat Methods. 2023; 20(3):327-330. DOI: 10.1038/s41592-023-01774-6. View

16.

Brunet M, Kraft M . Toward Understanding the Subcellular Distributions of Cholesterol and Sphingolipids Using High-Resolution NanoSIMS Imaging. Acc Chem Res. 2023; 56(7):752-762. DOI: 10.1021/acs.accounts.2c00760. View

17.

Kertesz V, Cahill J . Spatially resolved absolute quantitation in thin tissue by mass spectrometry. Anal Bioanal Chem. 2020; 413(10):2619-2636. DOI: 10.1007/s00216-020-02964-3. View

18.

Guo L, Dong J, Xu X, Wu Z, Zhang Y, Wang Y . Divide and Conquer: A Flexible Deep Learning Strategy for Exploring Metabolic Heterogeneity from Mass Spectrometry Imaging Data. Anal Chem. 2023; . PMC: 9878502. DOI: 10.1021/acs.analchem.2c04045. View

19.

Babu M, Snyder M . Multi-Omics Profiling for Health. Mol Cell Proteomics. 2023; 22(6):100561. PMC: 10220275. DOI: 10.1016/j.mcpro.2023.100561. View

20.

Zhao C, Dong J, Deng L, Tan Y, Jiang W, Cai Z . Molecular network strategy in multi-omics and mass spectrometry imaging. Curr Opin Chem Biol. 2022; 70:102199. DOI: 10.1016/j.cbpa.2022.102199. View