A method for restoring signals and revealing individual macromolecule states in cryo-ET, REST

Haonan Zhang, Yan Li, Yanan Liu, Dongyu Li, Lin Wang, Kai Song, Keyan Bao and Ping Zhu ()
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Haonan Zhang: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Yan Li: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Yanan Liu: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Dongyu Li: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Lin Wang: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Kai Song: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Keyan Bao: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences
Ping Zhu: CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Cryo-electron tomography (cryo-ET) is widely used to explore the 3D density of biomacromolecules. However, the heavy noise and missing wedge effect prevent directly visualizing and analyzing the 3D reconstructions. Here, we introduced REST, a deep learning strategy-based method to establish the relationship between low-quality and high-quality density and transfer the knowledge to restore signals in cryo-ET. Test results on the simulated and real cryo-ET datasets show that REST performs well in denoising and compensating the missing wedge information. The application in dynamic nucleosomes, presenting either in the form of individual particles or in the context of cryo-FIB nuclei section, indicates that REST has the capability to reveal different conformations of target macromolecules without subtomogram averaging. Moreover, REST noticeably improves the reliability of particle picking. These advantages enable REST to be a powerful tool for the straightforward interpretation of target macromolecules by visual inspection of the density and of a broad range of other applications in cryo-ET, such as segmentation, particle picking, and subtomogram averaging.

Date: 2023
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DOI: 10.1038/s41467-023-38539-w

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