Determination of nuclear position by the arrangement of actin filaments using deep generative networks

The cell nucleus is a dynamic structure that changes locales during cellular processes such as proliferation, differentiation, or migration 1 , and its mispositioning is a hallmark of several disorders 2,3 . 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 4 . However, this correlation between cytoskeleton organization and nuclear position has not, to date, been demonstrated, as it would require 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.