Speeding up Collective Cell Migration Using Deep Reinforcement Learning

Collective cell migration is a significant and complex phenomenon since it influences many fundamental biological processes. The coordination between leader cell and follower cell impact the speed of collective cell migration. However, there are still very few papers to study the effect of the stimulus signal released by the leader on the follower. Using 3D time-lapse microscopy image to keep track of the process of cell movement provides an unprecedented opportunity to systematically investigate and analysis collective cell migration. Traditional approach to study the process always based on reality scene, but are too time-consuming as the number of cells grows exponentially. Agent-based modeling is a robust framework that approximates cells as isotropic, elastic, and adhesive objects. In this paper, we use the agent-based modeling framework to build a simulation platform for cell movement. Its goal is to construct a biomimetic environment to prove the importance of stimulus signals between leader cell and follower cell. We use the recent popular deep reinforcement learning to train cells and to control the quantity of signal. By experimenting on single-follower and multi-follower, we get the conclusion that the number of stimulation signals is proportional to the speed of collective cell movement. This type of research provides a more diverse approach and thinking to study biological issues.

[1]  Ho-fung Leung,et al.  Efficient Convention Emergence through Decoupled Reinforcement Social Learning with Teacher-Student Mechanism , 2018, AAMAS.

[2]  Zi Wang,et al.  Deep reinforcement learning of cell movement in the early stage of C.elegans embryogenesis , 2018, Bioinform..

[3]  Anil A. Bharath,et al.  Deep Reinforcement Learning: A Brief Survey , 2017, IEEE Signal Processing Magazine.

[4]  Ho-fung Leung,et al.  The dynamics of reinforcement social learning in networked cooperative multiagent systems , 2017, Eng. Appl. Artif. Intell..

[5]  Miguel Ángel González Ballester,et al.  Virtual exploration of early stage atherosclerosis. , 2016, Bioinformatics.

[6]  Sandip Sen,et al.  Accelerating Norm Emergence Through Hierarchical Heuristic Learning , 2016, ECAI.

[7]  Miguel Ángel González Ballester,et al.  Virtual exploration of early stage atherosclerosis , 2016, Bioinform..

[8]  P. Friedl,et al.  Collective cell migration: guidance principles and hierarchies. , 2015, Trends in cell biology.

[9]  Pak Kin Wong,et al.  Notch1-Dll4 signaling and mechanical force regulate leader cell formation during collective cell migration , 2015, Nature Communications.

[10]  Shane Legg,et al.  Human-level control through deep reinforcement learning , 2015, Nature.

[11]  Takeomi Mizutani,et al.  Leader cells regulate collective cell migration via Rac activation in the downstream signaling of integrin β1 and PI3K , 2015, Scientific Reports.

[12]  A. Buguin,et al.  Interplay of RhoA and mechanical forces in collective cell migration driven by leader cells , 2014, Nature Cell Biology.

[13]  Z. Bao,et al.  De Novo Inference of Systems-Level Mechanistic Models of Development from Live-Imaging-Based Phenotype Analysis , 2014, Cell.

[14]  J. Camonis,et al.  Erratum: Interplay of RhoA and mechanical forces in collective cell migration driven by leader cells , 2014, Nature Cell Biology.

[15]  Alex Graves,et al.  Playing Atari with Deep Reinforcement Learning , 2013, ArXiv.

[16]  Yoko Suzuki,et al.  WDDD: Worm Developmental Dynamics Database , 2012, Nucleic Acids Res..

[17]  P. Friedl,et al.  Classifying collective cancer cell invasion , 2012, Nature Cell Biology.

[18]  Peter Friedl,et al.  Determinants of leader cells in collective cell migration. , 2010, Integrative biology : quantitative biosciences from nano to macro.

[19]  Stefan Hoehme,et al.  A cell-based simulation software for multi-cellular systems , 2010, Bioinform..

[20]  Revathi Ananthakrishnan,et al.  The Forces Behind Cell Movement , 2007, International journal of biological sciences.

[21]  Peter Dayan,et al.  Q-learning , 1992, Machine Learning.

[22]  Andrew W. Moore,et al.  Reinforcement Learning: A Survey , 1996, J. Artif. Intell. Res..

[23]  H. Lodish Molecular Cell Biology , 1986 .