CryoGEN: Generative Energy-based Models for Cryogenic Electron Tomography Reconstruction

Cryogenic electron tomography (Cryo-ET) is a powerful technique for visualizing subcellular structures in their native states. Nonetheless, its effectiveness is compromised by anisotropic resolution artifacts caused by the missing-wedge effect. To address this, IsoNet, a deep learning-based method, proposes iteratively reconstructing the missing-wedge information. While successful, IsoNet's dependence on recursive prediction updates often leads to training instability and model divergence. In this study, we introduce CryoGEN—an energy-based probabilistic model that not only mitigates resolution anisotropy but also removes the need for recursive subtomogram averaging, delivering an approximate *10*$\times$ speedup for training. Evaluations across various biological datasets, including immature HIV-1 virions and ribosomes, demonstrate that CryoGEN significantly enhances structural completeness and interpretability of the reconstructed samples.