From qualitative data to correlation using deep generative networks: Demonstrating the relation of nuclear position with the arrangement of actin filaments

PLoS One. 2022 Jul 29;17(7):e0271056. doi: 10.1371/journal.pone.0271056. eCollection 2022.

Abstract

The cell nucleus is a dynamic structure that changes locales during cellular processes such as proliferation, differentiation, or migration, and its mispositioning is a hallmark of several disorders. As with most mechanobiological activities of adherent cells, the repositioning and anchoring of the nucleus are presumed to be associated with the organization of the cytoskeleton, the network of protein filaments providing structural integrity to the cells. However, demonstrating this correlation between cytoskeleton organization and nuclear position requires the parameterization of the extraordinarily intricate cytoskeletal fiber arrangements. Here, we show that this parameterization and demonstration can be achieved outside the limits of human conceptualization, using generative network and raw microscope images, relying on machine-driven interpretation and selection of parameterizable features. The developed transformer-based architecture was able to generate high-quality, completed images of more than 8,000 cells, using only information on actin filaments, predicting the presence of a nucleus and its exact localization in more than 70 per cent of instances. Our results demonstrate one of the most basic principles of mechanobiology with a remarkable level of significance. They also highlight the role of deep learning as a powerful tool in biology beyond data augmentation and analysis, capable of interpreting-unconstrained by the principles of human reasoning-complex biological systems from qualitative data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton* / metabolism
  • Actins / metabolism
  • Cell Nucleus / metabolism
  • Cytoskeleton* / metabolism
  • Humans
  • Microtubules / metabolism

Substances

  • Actins

Grants and funding

The Singaporean Ministry of Education has supported this research through the MOE2018-T2-2-176 grant to Javier G. Fernandez.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.