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A Bayesian approach to single-particle electron cryo-tomography in RELION-4.0

★ ★ ★ ★ ☆

Paper Summary

Paperzilla title
RELION 4.0: Ditching 3D, sticking to 2D for sharper subtomograms!

This paper introduces a new Bayesian approach for subtomogram averaging that operates directly on 2D tilt series images within RELION 4.0. This method eliminates the need for missing wedge correction and offers improved accuracy for subtomogram alignment and classification, demonstrated by achieving resolutions sufficient for de novo atomic modeling in two test cases: the HIV immature capsid and the C. crescentus S-layer.

Explain Like I'm Five

Scientists found a new way to use a special computer program to make very clear pictures of tiny things, like parts of viruses. It's like taking many blurry photos and then using a clever trick to stack them up perfectly, making the final picture super sharp so they can see all the tiny pieces.

Possible Conflicts of Interest

None identified

Identified Limitations

Lack of explicit discussion of limitations
While the paper extensively describes the algorithm and its implementation, it lacks a dedicated discussion of the limitations.
Limited diversity of test cases
The paper would benefit from including more diverse test cases to showcase the general applicability of RELION 4.0. Different sample types and imaging conditions would strengthen the evaluation.
Missing comparison with other software packages
The paper does not include a comparison with other existing software packages besides NovaCTF and Warp. This would be helpful to put RELION 4.0's performance into context.

Rating Explanation

This paper presents a significant methodological advance in cryo-ET image processing. The shift to a 2D likelihood-based approach addresses limitations of previous 3D methods. The implementation in RELION 4.0 makes this powerful technique accessible to a wider audience. While the evaluation is limited to two case studies, the results are promising. The lack of a detailed discussion of limitations and a broader comparison with other software packages prevent a rating of 5.

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File Information

Original Title: A Bayesian approach to single-particle electron cryo-tomography in RELION-4.0
Uploaded: July 14, 2025 at 11:28 AM
Privacy: Public