Cell movement in the early phase of C. elegans development is regulated by a highly complex process in which a set of rules and connections are formulated at distinct scales. Previous efforts have demonstrated that agent-based, multi-scale modeling systems can integrate physical and biological rules and provide new avenues to study developmental systems. However, the application of these systems to model cell movement is still challenging and requires a comprehensive understanding of regulation networks at the right scales. Recent developments in deep learning and reinforcement learning provide an unprecedented opportunity to explore cell movement using 3D time-lapse microscopy images. We presented a deep reinforcement learning approach within an agent-based modeling system to characterize cell movement in the embryonic development of C. elegans . We tested our model through two scenarios within real developmental processes: the anterior movement of the Cpaaa cell via intercalation and the restoration of the superficial left-right symmetry. Our modeling system overcame the local optimization problems encountered by traditional rule-based, agent-based modeling by using greedy algorithms. It also overcame the computational challenges in the action selection which has been plagued by the traditional tabular-based reinforcement learning approach. Our system can automatically explore the cell movement path by using live microscopy images and it can provide a unique capability to model cell movement scenarios where regulatory mechanisms are not well studied. In addition, our system can be used to explore potential paths of a cell under different regulatory mechanisms or to facilitate new hypotheses for explaining certain cell movement behaviors .
Cell movement in the early phase of C. elegans development is regulated by a highly complex process in which a set of rules and connections are formulated at distinct scales. Previous efforts have shown that agent-based, multi-scale modeling systems can integrate physical and biological rules and provide new avenues to study developmental systems. However, the application of these systems to model cell movement is still challenging and requires a comprehensive understanding of regulation networks at the right scales. Recent developments in deep learning and reinforcement learning provide an unprecedented opportunity to explore cell movement using 3D time-lapse images. We present a deep reinforcement learning approach within an ABM system to characterize cell movement in C. elegans embryogenesis. Our modeling system captures the complexity of cell movement patterns in the embryo and overcomes the local optimization problem encountered by traditional rule-based, ABM that uses greedy algorithms. We tested our model with two real developmental processes: the anterior movement of the Cpaaa cell via intercalation and the rearrangement of the left-right asymmetry. In the first case, model results showed that Cpaaa's intercalation is an active directional cell movement caused by the continuous effects from a longer distance, as opposed to a passive movement caused by neighbor cell movements. This is because the learning-based simulation found that a passive movement model could not lead Cpaaa to the predefined destination. In the second case, a leader-follower mechanism well explained the collective cell movement pattern. These results showed that our approach to introduce deep reinforcement learning into ABM can test regulatory mechanisms by exploring cell migration paths in a reverse engineering perspective. This model opens new doors to explore large datasets generated by live imaging .
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demonstrated
shown
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microscopy
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presented
present
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agent-based modeling
ABM
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the embryonic development of
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embryogenesis. Our modeling system captures the complexity of cell movement patterns in the embryo and overcomes the local optimization problem encountered by traditional rule-based, ABM that uses greedy algorithms.
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through two scenarios within
with two
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restoration of the superficial
rearrangement of the
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symmetry. Our modeling system overcame the local optimization problems encountered by traditional rule-based, agent-based modeling by using greedy algorithms. It also overcame the computational challenges in the action selection which has been plagued by the traditional tabular-based reinforcement learning approach. Our system can automatically explore the cell movement path by using live microscopy images and it can provide a unique capability to model cell movement scenarios where regulatory mechanisms are not well studied. In addition, our system can be used to explore potential paths of a cell under different regulatory mechanisms or to facilitate new hypotheses for explaining certain cell movement behaviors
asymmetry. In the first case, model results showed that Cpaaa's intercalation is an active directional cell movement caused by the continuous effects from a longer distance, as opposed to a passive movement caused by neighbor cell movements. This is because the learning-based simulation found that a passive movement model could not lead Cpaaa to the predefined destination. In the second case, a leader-follower mechanism well explained the collective cell movement pattern. These results showed that our approach to introduce deep reinforcement learning into ABM can test regulatory mechanisms by exploring cell migration paths in a reverse engineering perspective. This model opens new doors to explore large datasets generated by live imaging