Evaluation of methods for generative modeling of cell and nuclear shape

Bioinformatics. 2019 Jul 15;35(14):2475-2485. doi: 10.1093/bioinformatics/bty983.

Abstract

Motivation: Cell shape provides both geometry for, and a reflection of, cell function. Numerous methods for describing and modeling cell shape have been described, but previous evaluation of these methods in terms of the accuracy of generative models has been limited.

Results: Here we compare traditional methods and deep autoencoders to build generative models for cell shapes in terms of the accuracy with which shapes can be reconstructed from models. We evaluated the methods on different collections of 2D and 3D cell images, and found that none of the methods gave accurate reconstructions using low dimensional encodings. As expected, much higher accuracies were observed using high dimensional encodings, with outline-based methods significantly outperforming image-based autoencoders. The latter tended to encode all cells as having smooth shapes, even for high dimensions. For complex 3D cell shapes, we developed a significant improvement of a method based on the spherical harmonic transform that performs significantly better than other methods. We obtained similar results for the joint modeling of cell and nuclear shape. Finally, we evaluated the modeling of shape dynamics by interpolation in the shape space. We found that our modified method provided lower deformation energies along linear interpolation paths than other methods. This allows practical shape evolution in high dimensional shape spaces. We conclude that our improved spherical harmonic based methods are preferable for cell and nuclear shape modeling, providing better representations, higher computational efficiency and requiring fewer training images than deep learning methods.

Availability and implementation: All software and data is available at http://murphylab.cbd.cmu.edu/software.

Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cell Nucleus
  • Imaging, Three-Dimensional
  • Software*