Abstract:Epithelial tissues dynamically reshape through local mechanical interactions among cells, a process well captured by vertex models. Yet their many tunable parameters make inference and optimization challenging, motivating computational frameworks that flexibly model and learn tissue mechanics. We introduce VertAX, a differentiable JAX-based framework for vertex-modeling of confluent epithelia. VertAX provides automatic differentiation, GPU acceleration, and end-to-end bilevel optimization for forward simulation, parameter inference, and inverse mechanical design. Users can define arbitrary energy and cost functions in pure Python, enabling seamless integration with machine-learning pipelines. We demonstrate VertAX on three representative tasks: (i) forward modeling of tissue morphogenesis, (ii) mechanical parameter inference, and (iii) inverse design of tissue-scale behaviors. We benchmark three differentiation strategies-automatic differentiation, implicit differentiation, and equilibrium propagation-showing that the latter can approximate gradients using repeated forward, adjoint-free simulations alone, offering a simple route for extending inverse biophysical problems to non-differentiable simulators with limited additional engineering effort.
Abstract:Three-dimensional biological microscopy has significantly advanced our understanding of complex biological structures. However, limitations due to microscopy techniques, sample properties or phototoxicity often result in poor z-resolution, hindering accurate cellular measurements. Here, we introduce ZAugNet, a fast, accurate, and self-supervised deep learning method for enhancing z-resolution in biological images. By performing nonlinear interpolation between consecutive slices, ZAugNet effectively doubles resolution with each iteration. Compared on several microscopy modalities and biological objects, it outperforms competing methods on most metrics. Our method leverages a generative adversarial network (GAN) architecture combined with knowledge distillation to maximize prediction speed without compromising accuracy. We also developed ZAugNet+, an extended version enabling continuous interpolation at arbitrary distances, making it particularly useful for datasets with nonuniform slice spacing. Both ZAugNet and ZAugNet+ provide high-performance, scalable z-slice augmentation solutions for large-scale 3D imaging. They are available as open-source frameworks in PyTorch, with an intuitive Colab notebook interface for easy access by the scientific community.