Recognition and reconstruction of cell differentiation patterns with deep learning

PLoS Comput Biol. 2023 Oct 27;19(10):e1011582. doi: 10.1371/journal.pcbi.1011582. eCollection 2023 Oct.

Abstract

Cell lineage decisions occur in three-dimensional spatial patterns that are difficult to identify by eye. There is an ongoing effort to replicate such patterns using mathematical modeling. One approach uses long ranging cell-cell communication to replicate common spatial arrangements like checkerboard and engulfing patterns. In this model, the cell-cell communication has been implemented as a signal that disperses throughout the tissue. On the other hand, machine learning models have been developed for pattern recognition and pattern reconstruction tasks. We combined synthetic data generated by the mathematical model with spatial summary statistics and deep learning algorithms to recognize and reconstruct cell fate patterns in organoids of mouse embryonic stem cells. Application of Moran's index and pair correlation functions for in vitro and synthetic data from the model showed local clustering and radial segregation. To assess the patterns as a whole, a graph neural network was developed and trained on synthetic data from the model. Application to in vitro data predicted a low signal dispersion value. To test this result, we implemented a multilayer perceptron for the prediction of a given cell fate based on the fates of the neighboring cells. The results show a 70% accuracy of cell fate imputation based on the nine nearest neighbors of a cell. Overall, our approach combines deep learning with mathematical modeling to link cell fate patterns with potential underlying mechanisms.

MeSH terms

  • Algorithms
  • Animals
  • Cell Differentiation
  • Deep Learning*
  • Mice
  • Models, Theoretical
  • Neural Networks, Computer

Grants and funding

SCF acknowledges funding from the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) project number 470129398 and start-up funding RAC/2020 from the University of Wuerzburg. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.