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Title: Hierarchical deep reinforcement learning reveals a modular mechanism of cell movement

Abstract

Time-lapse images of cells and tissues contain rich information about dynamic cell behaviours, which reflect the underlying processes of proliferation, differentiation and morphogenesis. However, we lack computational tools for effective inference. Here we exploit deep reinforcement learning (DRL) to infer cell–cell interactions and collective cell behaviours in tissue morphogenesis from three-dimensional (3D) time-lapse images. We use hierarchical DRL (HDRL), known for multiscale learning and data efficiency, to examine cell migrations based on images with a ubiquitous nuclear label and simple rules formulated from empirical statistics of the images. When applied to Caenorhabditis elegans embryogenesis, HDRL reveals a multiphase, modular organization of cell movement. Imaging with additional cellular markers confirms the modular organization as a novel migration mechanism, which we term sequential rosettes. Furthermore, HDRL forms a transferable model that successfully differentiates sequential rosettes-based migration from others. Our study demonstrates a powerful approach to infer the underlying biology from time-lapse imaging without prior knowledge.

Authors:
 [1];  [2]; ORCiD logo [3];  [1];  [2]
  1. Univ. of Tennessee, Knoxville, TN (United States)
  2. Sloan Kettering Inst., New York, NY (United States)
  3. Univ. of Tennessee, Knoxville, TN (United States); Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE Office of Science (SC); National Institutes of Health (NIH)
OSTI Identifier:
1869083
Grant/Contract Number:  
AC05-00OR22725; R01GM097576; P30CA008748
Resource Type:
Accepted Manuscript
Journal Name:
Nature Machine Intelligence
Additional Journal Information:
Journal Volume: 4; Journal Issue: 1; Journal ID: ISSN 2522-5839
Publisher:
Springer Nature
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 97 MATHEMATICS AND COMPUTING; body patterning; machine learning

Citation Formats

Wang, Zi, Xu, Yichi, Wang, Dali, Yang, Jiawei, and Bao, Zhirong. Hierarchical deep reinforcement learning reveals a modular mechanism of cell movement. United States: N. p., 2022. Web. doi:10.1038/s42256-021-00431-x.
Wang, Zi, Xu, Yichi, Wang, Dali, Yang, Jiawei, & Bao, Zhirong. Hierarchical deep reinforcement learning reveals a modular mechanism of cell movement. United States. https://doi.org/10.1038/s42256-021-00431-x
Wang, Zi, Xu, Yichi, Wang, Dali, Yang, Jiawei, and Bao, Zhirong. Mon . "Hierarchical deep reinforcement learning reveals a modular mechanism of cell movement". United States. https://doi.org/10.1038/s42256-021-00431-x. https://www.osti.gov/servlets/purl/1869083.
@article{osti_1869083,
title = {Hierarchical deep reinforcement learning reveals a modular mechanism of cell movement},
author = {Wang, Zi and Xu, Yichi and Wang, Dali and Yang, Jiawei and Bao, Zhirong},
abstractNote = {Time-lapse images of cells and tissues contain rich information about dynamic cell behaviours, which reflect the underlying processes of proliferation, differentiation and morphogenesis. However, we lack computational tools for effective inference. Here we exploit deep reinforcement learning (DRL) to infer cell–cell interactions and collective cell behaviours in tissue morphogenesis from three-dimensional (3D) time-lapse images. We use hierarchical DRL (HDRL), known for multiscale learning and data efficiency, to examine cell migrations based on images with a ubiquitous nuclear label and simple rules formulated from empirical statistics of the images. When applied to Caenorhabditis elegans embryogenesis, HDRL reveals a multiphase, modular organization of cell movement. Imaging with additional cellular markers confirms the modular organization as a novel migration mechanism, which we term sequential rosettes. Furthermore, HDRL forms a transferable model that successfully differentiates sequential rosettes-based migration from others. Our study demonstrates a powerful approach to infer the underlying biology from time-lapse imaging without prior knowledge.},
doi = {10.1038/s42256-021-00431-x},
journal = {Nature Machine Intelligence},
number = 1,
volume = 4,
place = {United States},
year = {Mon Jan 10 00:00:00 EST 2022},
month = {Mon Jan 10 00:00:00 EST 2022}
}

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