Missing Wedge Completion via Unsupervised Learning with Coordinate Networks

Abstract

Cryogenic electron tomography (cryoET) is a powerful tool in structural biology, enabling detailed 3D imaging of biological specimens at a resolution of nanometers. Despite its potential, cryoET faces challenges such as the missing wedge problem, which limits reconstruction quality due to incomplete data collection angles. Recently, supervised deep learning methods with convolutional neural networks (CNNs) have considerably addressed this issue; however, their pretraining renders them susceptible to inaccuracies and artifacts, particularly when representative training data is scarce. To overcome these limitations, we introduce a proof-of-concept unsupervised learning approach using coordinate networks (CNs) that optimizes network weights directly against input projections. This eliminates the need for pretraining, reducing reconstruction runtime by 3−20×compared to supervised methods. Our results from benchmarksin silicoshow improved shape completion and reduction of missing wedge artifacts, assessed through several voxel-based image quality metrics in real space and a novel directional Fourier Shell Correlation (FSC) metric. Our study illuminates benefits and considerations of both supervised and unsupervised approaches, guiding the development of improved reconstruction strategies.

CryoViT: Efficient Segmentation of Cryogenic Electron Tomograms with Vision Foundation Models

“…Just as the introduction of CNNs for cryoET analysis 21,50 sparked the development of numerous methods for automated particle picking 44 , subtomogram averaging 51,52,53 , and improved structural visualization by filling in the missing wedge 54 , including strategies leveraging alternative network models 55 , vision foundation models hold great promise for large-scale quantitative analyses of pleomorphic structures in tomograms. As such, they represent a paradigm shift in how cryoET will be used to further our understanding of fundamental biological processes.…”