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Learning the rules of collective cell migration using deep attention networks

Collective, coordinated cellular motions underpin key processes in all multicellular organisms, yet it has been difficult to simultaneously express the ‘rules’ behind these motions in clear, interpretable forms that effectively capture high-dimensional cell-cell interaction dynamics in a manner that...

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Autores principales: LaChance, Julienne, Suh, Kevin, Clausen, Jens, Cohen, Daniel J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106212/
https://www.ncbi.nlm.nih.gov/pubmed/35476698
http://dx.doi.org/10.1371/journal.pcbi.1009293
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author LaChance, Julienne
Suh, Kevin
Clausen, Jens
Cohen, Daniel J.
author_facet LaChance, Julienne
Suh, Kevin
Clausen, Jens
Cohen, Daniel J.
author_sort LaChance, Julienne
collection PubMed
description Collective, coordinated cellular motions underpin key processes in all multicellular organisms, yet it has been difficult to simultaneously express the ‘rules’ behind these motions in clear, interpretable forms that effectively capture high-dimensional cell-cell interaction dynamics in a manner that is intuitive to the researcher. Here we apply deep attention networks to analyze several canonical living tissues systems and present the underlying collective migration rules for each tissue type using only cell migration trajectory data. We use these networks to learn the behaviors of key tissue types with distinct collective behaviors—epithelial, endothelial, and metastatic breast cancer cells—and show how the results complement traditional biophysical approaches. In particular, we present attention maps indicating the relative influence of neighboring cells to the learned turning decisions of a ‘focal cell’–the primary cell of interest in a collective setting. Colloquially, we refer to this learned relative influence as ‘attention’, as it serves as a proxy for the physical parameters modifying the focal cell’s future motion as a function of each neighbor cell. These attention networks reveal distinct patterns of influence and attention unique to each model tissue. Endothelial cells exhibit tightly focused attention on their immediate forward-most neighbors, while cells in more expansile epithelial tissues are more broadly influenced by neighbors in a relatively large forward sector. Attention maps of ensembles of more mesenchymal, metastatic cells reveal completely symmetric attention patterns, indicating the lack of any particular coordination or direction of interest. Moreover, we show how attention networks are capable of detecting and learning how these rules change based on biophysical context, such as location within the tissue and cellular crowding. That these results require only cellular trajectories and no modeling assumptions highlights the potential of attention networks for providing further biological insights into complex cellular systems.
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spelling pubmed-91062122022-05-14 Learning the rules of collective cell migration using deep attention networks LaChance, Julienne Suh, Kevin Clausen, Jens Cohen, Daniel J. PLoS Comput Biol Research Article Collective, coordinated cellular motions underpin key processes in all multicellular organisms, yet it has been difficult to simultaneously express the ‘rules’ behind these motions in clear, interpretable forms that effectively capture high-dimensional cell-cell interaction dynamics in a manner that is intuitive to the researcher. Here we apply deep attention networks to analyze several canonical living tissues systems and present the underlying collective migration rules for each tissue type using only cell migration trajectory data. We use these networks to learn the behaviors of key tissue types with distinct collective behaviors—epithelial, endothelial, and metastatic breast cancer cells—and show how the results complement traditional biophysical approaches. In particular, we present attention maps indicating the relative influence of neighboring cells to the learned turning decisions of a ‘focal cell’–the primary cell of interest in a collective setting. Colloquially, we refer to this learned relative influence as ‘attention’, as it serves as a proxy for the physical parameters modifying the focal cell’s future motion as a function of each neighbor cell. These attention networks reveal distinct patterns of influence and attention unique to each model tissue. Endothelial cells exhibit tightly focused attention on their immediate forward-most neighbors, while cells in more expansile epithelial tissues are more broadly influenced by neighbors in a relatively large forward sector. Attention maps of ensembles of more mesenchymal, metastatic cells reveal completely symmetric attention patterns, indicating the lack of any particular coordination or direction of interest. Moreover, we show how attention networks are capable of detecting and learning how these rules change based on biophysical context, such as location within the tissue and cellular crowding. That these results require only cellular trajectories and no modeling assumptions highlights the potential of attention networks for providing further biological insights into complex cellular systems. Public Library of Science 2022-04-27 /pmc/articles/PMC9106212/ /pubmed/35476698 http://dx.doi.org/10.1371/journal.pcbi.1009293 Text en © 2022 LaChance et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
LaChance, Julienne
Suh, Kevin
Clausen, Jens
Cohen, Daniel J.
Learning the rules of collective cell migration using deep attention networks
title Learning the rules of collective cell migration using deep attention networks
title_full Learning the rules of collective cell migration using deep attention networks
title_fullStr Learning the rules of collective cell migration using deep attention networks
title_full_unstemmed Learning the rules of collective cell migration using deep attention networks
title_short Learning the rules of collective cell migration using deep attention networks
title_sort learning the rules of collective cell migration using deep attention networks
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106212/
https://www.ncbi.nlm.nih.gov/pubmed/35476698
http://dx.doi.org/10.1371/journal.pcbi.1009293
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