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Deep learning reveals cancer metastasis and therapeutic antibody targeting in whole body

Chenchen Pan, Oliver Schoppe, Arnaldo Parra-Damas, Ruiyao Cai, Mihail Ivilinov Todorov, Gabor Gondi, Bettina von Neubeck, Alireza Ghasemi, Madita Alice Reimer, Javier Coronel, Boyan K. Garvalov, Bjoern Menze, Reinhard Zeidler, Ali Ertürk
doi: https://doi.org/10.1101/541862
Chenchen Pan
1Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), Munich, Germany
3Graduate School of Neuroscience (GSN), Munich, Germany
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Oliver Schoppe
2Center for Translational Cancer Research (TranslaTUM) & Department of Computer Science
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Arnaldo Parra-Damas
1Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), Munich, Germany
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Ruiyao Cai
1Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), Munich, Germany
3Graduate School of Neuroscience (GSN), Munich, Germany
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Mihail Ivilinov Todorov
1Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), Munich, Germany
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Gabor Gondi
4Helmholtz Zentrum München, Research Unit Gene Vectors, Munich, Germany
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Bettina von Neubeck
4Helmholtz Zentrum München, Research Unit Gene Vectors, Munich, Germany
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Alireza Ghasemi
1Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), Munich, Germany
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Madita Alice Reimer
1Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), Munich, Germany
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Javier Coronel
2Center for Translational Cancer Research (TranslaTUM) & Department of Computer Science
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Boyan K. Garvalov
5Department of Microvascular Biology and Pathobiology, European Center for Angioscience (ECAS), Medical Faculty Mannheim, University of Heidelberg, Germany
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Bjoern Menze
2Center for Translational Cancer Research (TranslaTUM) & Department of Computer Science
8Munich School of Bioengineering, Technical University of Munich, Munich, Germany
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Reinhard Zeidler
4Helmholtz Zentrum München, Research Unit Gene Vectors, Munich, Germany
6Department for Otorhinolaryngology, Klinikum der Universität München, Munich, Germany
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Ali Ertürk
1Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig Maximilian University of Munich (LMU), Munich, Germany
3Graduate School of Neuroscience (GSN), Munich, Germany
7Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
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SUMMARY

Reliable detection of disseminated tumor cells and of the biodistribution of tumor-targeting therapeutic antibodies within the entire body has long been needed to better understand and treat cancer metastasis. Here, we developed an integrated pipeline for automated quantification of cancer metastases and therapeutic antibody targeting, named DeepMACT. First, we enhanced the fluorescent signal of tumor cells more than 100-fold by applying the vDISCO method to image single cancer cells in intact transparent mice. Second, we developed deep learning algorithms for automated quantification of metastases with an accuracy matching human expert manual annotation. Deep learning-based quantifications in a model of spontaneous metastasis using human breast cancer cells allowed us to systematically analyze clinically relevant features such as size, shape, spatial distribution, and the degree to which metastases are targeted by a therapeutic monoclonal antibody in whole mice. DeepMACT can thus considerably improve the discovery of effective therapeutic strategies for metastatic cancer.

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Graphical AbstractSupplementary Movies and deep learning algorithms of DeepMACT are available at http://discotechnologies.org/DeepMACT/

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 February 05, 2019.
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Deep learning reveals cancer metastasis and therapeutic antibody targeting in whole body
Chenchen Pan, Oliver Schoppe, Arnaldo Parra-Damas, Ruiyao Cai, Mihail Ivilinov Todorov, Gabor Gondi, Bettina von Neubeck, Alireza Ghasemi, Madita Alice Reimer, Javier Coronel, Boyan K. Garvalov, Bjoern Menze, Reinhard Zeidler, Ali Ertürk
bioRxiv 541862; doi: https://doi.org/10.1101/541862
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Deep learning reveals cancer metastasis and therapeutic antibody targeting in whole body
Chenchen Pan, Oliver Schoppe, Arnaldo Parra-Damas, Ruiyao Cai, Mihail Ivilinov Todorov, Gabor Gondi, Bettina von Neubeck, Alireza Ghasemi, Madita Alice Reimer, Javier Coronel, Boyan K. Garvalov, Bjoern Menze, Reinhard Zeidler, Ali Ertürk
bioRxiv 541862; doi: https://doi.org/10.1101/541862

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