Spatial mapping of the brain metabolome lipidome and glycome

Abstract Metabolites, lipids, and glycans are fundamental but interconnected classes of biomolecules that form the basis of the metabolic network. These molecules are dynamically channeled through multiple pathways that govern cellular physiology and pathology. Here, we present a framework for the s...

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Main Authors: Harrison A. Clarke, Xin Ma, Cameron J. Shedlock, Terrymar Medina, Tara R. Hawkinson, Lei Wu, Roberto A. Ribas, Shannon Keohane, Sakthivel Ravi, Jennifer L. Bizon, Sara N. Burke, Jose Francisco Abisambra, Matthew E. Merritt, Boone M. Prentice, Craig W. Vander Kooi, Matthew S. Gentry, Li Chen, Ramon C. Sun
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-59487-7
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author Harrison A. Clarke
Xin Ma
Cameron J. Shedlock
Terrymar Medina
Tara R. Hawkinson
Lei Wu
Roberto A. Ribas
Shannon Keohane
Sakthivel Ravi
Jennifer L. Bizon
Sara N. Burke
Jose Francisco Abisambra
Matthew E. Merritt
Boone M. Prentice
Craig W. Vander Kooi
Matthew S. Gentry
Li Chen
Ramon C. Sun
author_facet Harrison A. Clarke
Xin Ma
Cameron J. Shedlock
Terrymar Medina
Tara R. Hawkinson
Lei Wu
Roberto A. Ribas
Shannon Keohane
Sakthivel Ravi
Jennifer L. Bizon
Sara N. Burke
Jose Francisco Abisambra
Matthew E. Merritt
Boone M. Prentice
Craig W. Vander Kooi
Matthew S. Gentry
Li Chen
Ramon C. Sun
author_sort Harrison A. Clarke
collection DOAJ
description Abstract Metabolites, lipids, and glycans are fundamental but interconnected classes of biomolecules that form the basis of the metabolic network. These molecules are dynamically channeled through multiple pathways that govern cellular physiology and pathology. Here, we present a framework for the simultaneous spatial analysis of the metabolome, lipidome, and glycome from a single tissue section using mass spectrometry imaging. This workflow integrates a computational platform, the Spatial Augmented Multiomics Interface (Sami), which enables multiomics integration, high-dimensional clustering, spatial anatomical mapping of matched molecular features, and metabolic pathway enrichment. To demonstrate the utility of this approach, we applied Sami to evaluate metabolic diversity across distinct brain regions and to compare wild-type and Ps19 Alzheimer’s disease (AD) mouse models. Our findings reveal region-specific metabolic demands in the normal brain and highlight metabolic dysregulation in the Ps19 model, providing insights into the biochemical alterations associated with neurodegeneration.
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spelling doaj-art-247ee4ce6ccb4c8aac71887337acebe52025-08-20T03:48:06ZengNature PortfolioNature Communications2041-17232025-05-0116111310.1038/s41467-025-59487-7Spatial mapping of the brain metabolome lipidome and glycomeHarrison A. Clarke0Xin Ma1Cameron J. Shedlock2Terrymar Medina3Tara R. Hawkinson4Lei Wu5Roberto A. Ribas6Shannon Keohane7Sakthivel Ravi8Jennifer L. Bizon9Sara N. Burke10Jose Francisco Abisambra11Matthew E. Merritt12Boone M. Prentice13Craig W. Vander Kooi14Matthew S. Gentry15Li Chen16Ramon C. Sun17Department of Biochemistry & Molecular Biology, College of Medicine, University of FloridaDepartment of Biochemistry & Molecular Biology, College of Medicine, University of FloridaDepartment of Biochemistry & Molecular Biology, College of Medicine, University of FloridaDepartment of Biochemistry & Molecular Biology, College of Medicine, University of FloridaDepartment of Biochemistry & Molecular Biology, College of Medicine, University of FloridaDepartment of Biochemistry & Molecular Biology, College of Medicine, University of FloridaDepartment of Biochemistry & Molecular Biology, College of Medicine, University of FloridaDepartment of Biochemistry & Molecular Biology, College of Medicine, University of FloridaDepartment of Neuroscience, University of FloridaDepartment of Neuroscience, University of FloridaDepartment of Neuroscience, University of FloridaDepartment of Neuroscience, University of FloridaDepartment of Biochemistry & Molecular Biology, College of Medicine, University of FloridaDepartment of Chemistry, University of FloridaDepartment of Biochemistry & Molecular Biology, College of Medicine, University of FloridaDepartment of Biochemistry & Molecular Biology, College of Medicine, University of FloridaDepartment of Biostatistics College of Public Health and Health Professions & College of Medicine, University of FloridaDepartment of Biochemistry & Molecular Biology, College of Medicine, University of FloridaAbstract Metabolites, lipids, and glycans are fundamental but interconnected classes of biomolecules that form the basis of the metabolic network. These molecules are dynamically channeled through multiple pathways that govern cellular physiology and pathology. Here, we present a framework for the simultaneous spatial analysis of the metabolome, lipidome, and glycome from a single tissue section using mass spectrometry imaging. This workflow integrates a computational platform, the Spatial Augmented Multiomics Interface (Sami), which enables multiomics integration, high-dimensional clustering, spatial anatomical mapping of matched molecular features, and metabolic pathway enrichment. To demonstrate the utility of this approach, we applied Sami to evaluate metabolic diversity across distinct brain regions and to compare wild-type and Ps19 Alzheimer’s disease (AD) mouse models. Our findings reveal region-specific metabolic demands in the normal brain and highlight metabolic dysregulation in the Ps19 model, providing insights into the biochemical alterations associated with neurodegeneration.https://doi.org/10.1038/s41467-025-59487-7
spellingShingle Harrison A. Clarke
Xin Ma
Cameron J. Shedlock
Terrymar Medina
Tara R. Hawkinson
Lei Wu
Roberto A. Ribas
Shannon Keohane
Sakthivel Ravi
Jennifer L. Bizon
Sara N. Burke
Jose Francisco Abisambra
Matthew E. Merritt
Boone M. Prentice
Craig W. Vander Kooi
Matthew S. Gentry
Li Chen
Ramon C. Sun
Spatial mapping of the brain metabolome lipidome and glycome
Nature Communications
title Spatial mapping of the brain metabolome lipidome and glycome
title_full Spatial mapping of the brain metabolome lipidome and glycome
title_fullStr Spatial mapping of the brain metabolome lipidome and glycome
title_full_unstemmed Spatial mapping of the brain metabolome lipidome and glycome
title_short Spatial mapping of the brain metabolome lipidome and glycome
title_sort spatial mapping of the brain metabolome lipidome and glycome
url https://doi.org/10.1038/s41467-025-59487-7
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