Joint Denoising of Cryo-EM Projection Images using Polar Transformers
Joakim And\'en, Justus Sagem\"uller

TL;DR
This paper introduces the polar transformer, a neural network architecture that leverages polar representations and transformers to improve denoising of cryo-EM projection images, enabling better reconstruction from noisy data.
Contribution
The work presents a novel neural network architecture that respects rotational symmetry and enhances end-to-end cryo-EM image denoising and reconstruction.
Findings
Achieves up to 2x reduction in MSE at SNR 0.02
Effectively learns discriminative features for clustering and alignment
Demonstrates potential for improved data-driven reconstruction in cryo-EM
Abstract
Many imaging modalities involve reconstruction of unknown objects from collections of noisy projections related by random rotations. In one of these modalities, cryogenic electron microscopy (cryo-EM), the extremely low signal-to-noise ratio (SNR) makes integration of information from multiple images crucial. Existing approaches to cryo-EM processing, however, either rely on handcrafted priors or apply deep learning only on select portions of the pipeline, such as particle picking, micrograph denoising, or refinement. A fully end-to-end reconstruction approach requires a neural network architecture that integrates information from multiple images while respecting the rotational symmetry of the measurement process. In this work, we introduce the polar transformer, a new neural network architecture that combines polar representations and transformers along with a convolutional attention…
Peer Reviews
Decision·Submitted to ICLR 2025
+++Proposed method (using an invariant network to jointly denoise multiple images in the polar domain) is novel and well-motivated
---Contextualization/Practical relevance: The manuscript states the single particle reconstruction pipeline "involves first extracting images of individual particles from the micrographs, denoising these images, estimating their corresponding viewing directions, and then reconstructing a 3D density map". However, it is my understanding that modern reconstruction techniques (e.g., expectation maximization [A]) marginalize over the various view directions and avoid denoising the 2D projections all
1. Leveraging polar representation can simplify the denoising task by translating rotational variance into angular shifts. This approach is promising for denoising given the rotational nature of cryo-EM. 2. Using a dataset of 5,000,000 images strengthens the model's robustness and enables it to learn effectively from diverse viewing angles. 3. Testing both Gaussian and Poisson noise further validates the proposed model. 4. Testing both CNN and transformer architectures increases the reliability
1. Some key details in the approximations lack mathematical measurements (see Q1). 2. Results are only compared to the Wiener filter method. Including comparisons with more state-of-the-art methods would be better. 3. Adding a mathematical proof explaining why and how polar representation improves denoising accuracy would strengthen the theoretical foundation of the approach (Related to Q3). 4. At leat two typos. (See Q5).
The paper is clearly written and provides a great introduction to the problem of denoising in cryo-EM reconstruction. The authors introduce their method step-by-step, making it easy to follow the rationale of each of their design choices. The use of a polar representation to achieve rotational equivariance is innovative and well-founded, facilitating deep learning-based denoising that can leverage the signal from images taken at the same viewing angle without requiring an explicit preprocessing
While the theoretical foundation of the method is convincing, the experimental validation of its effectiveness is lacking. The only baseline comparison is to Wiener filtering, with no comparisons to other deep learning-based methods, despite several being mentioned in the related work section. I suggest to include a comparison to at least one of the deep-learning based methods, such as the DnCNN (Zhang et al., 2017) or a U-Net denoiser adapted for cryoEM data. Further, all experiments are con
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Taxonomy
TopicsAdvanced Electron Microscopy Techniques and Applications · Advanced X-ray Imaging Techniques · Digital Holography and Microscopy
