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

Open access
Zivanov, Jasenko, Otón, Joaquín, Ke, Zunlong, von Kügelgen, Andriko, Pyle, Euan, Qu, Kun, Morado, Dustin, Castaño-Díez, Daniel, Zanetti, Giulia, Bharat, Tanmay AM, Briggs, John AG, Scheres, Sjors HW·2022·eLife

Abstract

We present a new approach for macromolecular structure determination from multiple particles in electron cryo-tomography (cryo-ET) data sets. Whereas existing subtomogram averaging approaches are based on 3D data models, we propose to optimise a regularised likelihood target that approximates a function of the 2D experimental images. In addition, analogous to Bayesian polishing and contrast transfer function (CTF) refinement in single-particle analysis, we describe the approaches that exploit the increased signal-to-noise ratio in the averaged structure to optimise tilt-series alignments, beam-induced motions of the particles throughout the tilt-series acquisition, defoci of the individual particles, as well as higher-order optical aberrations of the microscope. Implementation of our approaches in the open-source software package RELION aims to facilitate their general use, particularly for those researchers who are already familiar with its single-particle analysis tools. We illustrate for three applications that our approaches allow structure determination from cryo-ET data to resolutions sufficient for de novo atomic modelling.

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Authors
Zivanov, J., Otón, J., Ke, Z., von Kügelgen, A., Pyle, E., Qu, K., Morado, D., Castaño-Díez, D., Zanetti, G., Bharat, T. A., Briggs, J. A., & Scheres, S. H.
Venue
eLife
Published
2022-12-05
Volume
11
ISSN
2050-084X (ISSN-L)
OpenAlex
W4310775336
Cited by
339
References
0
FWCI
31.86
Type
journal article
Language
en
Open access
gold

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