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Transformer-based spatial-temporal detection of apoptotic cell death in live-cell imaging

Alain Pulfer, Diego Ulisse Pizzagalli, Paolo Armando Gagliardi, Lucien Hinderling, Paul Lopez, Romaniya Zayats, Pau Carrillo-Barberà, Paola Antonello, Miguel Palomino-Segura, Alessandro Giusti, Marcus Thelen, Luca Maria Gambardella, Thomas T. Murooka, View ORCID ProfileOlivier Pertz, Rolf Krause, Santiago Fernandez Gonzalez
doi: https://doi.org/10.1101/2022.11.23.517318
Alain Pulfer
1Institute for Research in Biomedicine, Faculty of Biomedical Sciences, USI—Switzerland
2Department of Information Technology and Electrical Engineering, ETH Zurich—Switzerland
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Diego Ulisse Pizzagalli
1Institute for Research in Biomedicine, Faculty of Biomedical Sciences, USI—Switzerland
3Euler Institute, USI—Switzerland
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Paolo Armando Gagliardi
4Institute of Cell Biology, University of Bern—Switzerland
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Lucien Hinderling
4Institute of Cell Biology, University of Bern—Switzerland
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Paul Lopez
5University of Manitoba, Winnipeg—Canada
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Romaniya Zayats
5University of Manitoba, Winnipeg—Canada
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Pau Carrillo-Barberà
1Institute for Research in Biomedicine, Faculty of Biomedical Sciences, USI—Switzerland
6Instituto de Biotecnología y Biomedicina (BioTecMed), Universitat de València—Spain
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Paola Antonello
1Institute for Research in Biomedicine, Faculty of Biomedical Sciences, USI—Switzerland
4Institute of Cell Biology, University of Bern—Switzerland
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Miguel Palomino-Segura
7Centro Nacional de Investigaciones Cardiovasculares—Spain
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Alessandro Giusti
8Dalle Molle Institute for Artificial Intelligence, IDSIA—Switzerland
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Marcus Thelen
1Institute for Research in Biomedicine, Faculty of Biomedical Sciences, USI—Switzerland
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Luca Maria Gambardella
8Dalle Molle Institute for Artificial Intelligence, IDSIA—Switzerland
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Thomas T. Murooka
5University of Manitoba, Winnipeg—Canada
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Olivier Pertz
4Institute of Cell Biology, University of Bern—Switzerland
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  • ORCID record for Olivier Pertz
Rolf Krause
3Euler Institute, USI—Switzerland
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Santiago Fernandez Gonzalez
1Institute for Research in Biomedicine, Faculty of Biomedical Sciences, USI—Switzerland
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  • For correspondence: [email protected]
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Abstract

Intravital microscopy has revolutionized live cell imaging by allowing the study of spatial-temporal cell dynamics in living animals. However, the complexity of the data generated by this technology has limited the development of effective computational tools to identify and quantify cell processes. Amongst them, apoptosis is a crucial form of regulated cell death involved in tissue homeostasis and host defense. Live-cell imaging enabled the study of apoptosis at the cellular level, enhancing our understanding of its spatial-temporal regulation. However, at present, no computational method can deliver label-free detection of apoptosis in microscopy time-lapses. To overcome this limitation, we developed ADeS, a deep learning-based apoptosis detection system that employs the principle of activity recognition. We trained ADeS on extensive datasets containing more than 10,000 apoptotic instances collected both in vitro and in vivo, achieving a classification accuracy above 98% and outperforming state-of-the-art solutions. ADeS is the first method capable of detecting the location and duration of multiple apoptotic events in full microscopy time-lapses, surpassing human performance in the same task. We demonstrated the effectiveness and robustness of ADeS across various imaging modalities, cell types, and staining techniques. Finally, we employed ADeS to quantify cell survival in vitro and tissue damage in vivo, demonstrating its potential application in toxicity assays, treatment evaluation, and inflammatory dynamics. Our findings suggest that ADeS is a valuable tool for the accurate detection and quantification of apoptosis in live-cell imaging and, in particular, intravital microscopy data, providing insights into the complex spatial-temporal regulation of this process.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Title has been changed A novel Deep Learning classifier has been implemented surpassing in accuracy the previous one

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted June 23, 2023.
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Transformer-based spatial-temporal detection of apoptotic cell death in live-cell imaging
Alain Pulfer, Diego Ulisse Pizzagalli, Paolo Armando Gagliardi, Lucien Hinderling, Paul Lopez, Romaniya Zayats, Pau Carrillo-Barberà, Paola Antonello, Miguel Palomino-Segura, Alessandro Giusti, Marcus Thelen, Luca Maria Gambardella, Thomas T. Murooka, Olivier Pertz, Rolf Krause, Santiago Fernandez Gonzalez
bioRxiv 2022.11.23.517318; doi: https://doi.org/10.1101/2022.11.23.517318
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Transformer-based spatial-temporal detection of apoptotic cell death in live-cell imaging
Alain Pulfer, Diego Ulisse Pizzagalli, Paolo Armando Gagliardi, Lucien Hinderling, Paul Lopez, Romaniya Zayats, Pau Carrillo-Barberà, Paola Antonello, Miguel Palomino-Segura, Alessandro Giusti, Marcus Thelen, Luca Maria Gambardella, Thomas T. Murooka, Olivier Pertz, Rolf Krause, Santiago Fernandez Gonzalez
bioRxiv 2022.11.23.517318; doi: https://doi.org/10.1101/2022.11.23.517318

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