A multi-tissue longitudinal proteomics study to evaluate the suitability of post-mortem samples for pathophysiological research

Abstract Recent developments in mass spectrometry-based proteomics have established it as a robust tool for system-wide analyses essential for pathophysiological research. While post-mortem samples are a critical source for these studies, our understanding of how body decomposition influences the pr...

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Main Authors: Christian M. Beusch, Ken Braesch-Andersen, Ulrika Felldin, Pierre Sabatier, Anna Widgren, Jonas Bergquist, Karl-Henrik Grinnemo, Sergey Rodin
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-025-07515-z
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author Christian M. Beusch
Ken Braesch-Andersen
Ulrika Felldin
Pierre Sabatier
Anna Widgren
Jonas Bergquist
Karl-Henrik Grinnemo
Sergey Rodin
author_facet Christian M. Beusch
Ken Braesch-Andersen
Ulrika Felldin
Pierre Sabatier
Anna Widgren
Jonas Bergquist
Karl-Henrik Grinnemo
Sergey Rodin
author_sort Christian M. Beusch
collection DOAJ
description Abstract Recent developments in mass spectrometry-based proteomics have established it as a robust tool for system-wide analyses essential for pathophysiological research. While post-mortem samples are a critical source for these studies, our understanding of how body decomposition influences the proteome remains limited. Here, we have revisited published data and conducted a clinically relevant time-course experiment in mice, revealing organ-specific proteome regulation after death, with only a fraction of these changes linked to protein autolysis. The liver and spleen exhibit significant proteomic alterations within hours post-mortem, whereas the heart displays only modest changes. Additionally, subcellular compartmentalization leads to an unexpected surge in proteome alterations at the earliest post-mortem interval (PMI). Additionally, we have conducted a comprehensive analysis of semi-tryptic peptides, revealing distinct consensus motifs for different organs, indicating organ-specific post-mortem protease activity. In conclusion, our findings emphasize the critical importance of considering PMI effects when designing proteomics studies, as these effects may significantly overshadow the impacts of diseases. Preferably, the samples should be taken in the operation room, especially for studies including subcellular compartmentalization or trans-organ comparison. In single-organ studies, the planning should involve careful control of PMI.
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issn 2399-3642
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spelling doaj-art-90d139c9678f4cc6aa6eae81da91b9fa2025-01-19T12:35:43ZengNature PortfolioCommunications Biology2399-36422025-01-018111010.1038/s42003-025-07515-zA multi-tissue longitudinal proteomics study to evaluate the suitability of post-mortem samples for pathophysiological researchChristian M. Beusch0Ken Braesch-Andersen1Ulrika Felldin2Pierre Sabatier3Anna Widgren4Jonas Bergquist5Karl-Henrik Grinnemo6Sergey Rodin7Cardio-Thoracic Translational Medicine (CTTM) Lab, Department of Surgical Sciences, Uppsala UniversityCardio-Thoracic Translational Medicine (CTTM) Lab, Department of Surgical Sciences, Uppsala UniversityCardio-Thoracic Translational Medicine (CTTM) Lab, Department of Surgical Sciences, Uppsala UniversityCardio-Thoracic Translational Medicine (CTTM) Lab, Department of Surgical Sciences, Uppsala UniversityDepartment of Chemistry – BMC, Analytical Chemistry and Neurochemistry, Uppsala UniversityDepartment of Chemistry – BMC, Analytical Chemistry and Neurochemistry, Uppsala UniversityCardio-Thoracic Translational Medicine (CTTM) Lab, Department of Surgical Sciences, Uppsala UniversityCardio-Thoracic Translational Medicine (CTTM) Lab, Department of Surgical Sciences, Uppsala UniversityAbstract Recent developments in mass spectrometry-based proteomics have established it as a robust tool for system-wide analyses essential for pathophysiological research. While post-mortem samples are a critical source for these studies, our understanding of how body decomposition influences the proteome remains limited. Here, we have revisited published data and conducted a clinically relevant time-course experiment in mice, revealing organ-specific proteome regulation after death, with only a fraction of these changes linked to protein autolysis. The liver and spleen exhibit significant proteomic alterations within hours post-mortem, whereas the heart displays only modest changes. Additionally, subcellular compartmentalization leads to an unexpected surge in proteome alterations at the earliest post-mortem interval (PMI). Additionally, we have conducted a comprehensive analysis of semi-tryptic peptides, revealing distinct consensus motifs for different organs, indicating organ-specific post-mortem protease activity. In conclusion, our findings emphasize the critical importance of considering PMI effects when designing proteomics studies, as these effects may significantly overshadow the impacts of diseases. Preferably, the samples should be taken in the operation room, especially for studies including subcellular compartmentalization or trans-organ comparison. In single-organ studies, the planning should involve careful control of PMI.https://doi.org/10.1038/s42003-025-07515-z
spellingShingle Christian M. Beusch
Ken Braesch-Andersen
Ulrika Felldin
Pierre Sabatier
Anna Widgren
Jonas Bergquist
Karl-Henrik Grinnemo
Sergey Rodin
A multi-tissue longitudinal proteomics study to evaluate the suitability of post-mortem samples for pathophysiological research
Communications Biology
title A multi-tissue longitudinal proteomics study to evaluate the suitability of post-mortem samples for pathophysiological research
title_full A multi-tissue longitudinal proteomics study to evaluate the suitability of post-mortem samples for pathophysiological research
title_fullStr A multi-tissue longitudinal proteomics study to evaluate the suitability of post-mortem samples for pathophysiological research
title_full_unstemmed A multi-tissue longitudinal proteomics study to evaluate the suitability of post-mortem samples for pathophysiological research
title_short A multi-tissue longitudinal proteomics study to evaluate the suitability of post-mortem samples for pathophysiological research
title_sort multi tissue longitudinal proteomics study to evaluate the suitability of post mortem samples for pathophysiological research
url https://doi.org/10.1038/s42003-025-07515-z
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