Improved Denoising of Cryo-Electron Microscopy Micrographs with Simulation-Aware Pretraining

Cryo-electron microscopy (cryo-EM) has emerged as a potent technique for determining the structure and functionality of biological macromolecules. However, limited by the physical imaging conditions, such as low electron beam dose, micrographs in cryo-EM typically contend with an extremely low signal-to-noise ratio (SNR), impeding the efficiency and efficacy of subsequent analyses. Therefore, there is a growing demand for an efficient denoising algorithm designed for cryo-EM micrographs, aiming to enhance the quality of macromolecular analysis. However, owing to the absence of a comprehensive and well-defined dataset with ground truth images, supervised image denoising methods exhibit limited generalization when applied to experimental micrographs. To tackle this challenge, we introduce a simulation-aware image denoising (SaID) pretrained model designed to enhance the SNR of cryo-EM micrographs where the training is solely based on an accurately simulated dataset. First, we propose a parameter calibration algorithm for simulated dataset generation, aiming to align simulation parameters with those of experimental micrographs. Second, leveraging the accurately simulated dataset, we propose to train a deep general denoising model that can well generalize to real experimental cryo-EM micrographs. Comprehensive experimental results demonstrate that our pretrained denoising model achieves excellent denoising performance on experimental cryo-EM micrographs, significantly streamlining downstream analysis.