A Bayesian approach to beam-induced motion correction in cryo-EM single-particle analysis

By Jasenko Zivanov, Takanori Nakane, Sjors H. W. Scheres. 2018

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We present a new method to estimate the trajectories of particle motion and the amount of cumulative beam damage in electron cryo-microscopy (cryo-EM) single particle analysis. We model the motion within the sample through the use of Gaussian Process regression. This allows us to associate with each hypothetical set of particle trajectories a prior likelihood that favours spatially and temporally smooth motion without imposing hard constraints. This formulation enables us to express the a-posteriori likelihood of a set of particle trajectories as a product of that prior likelihood and an observation likelihood given by the data, and to then maximise this a-posteriori likelihood. Since our smoothness prior requires three parameters that describe the statistics of the observed motion, we also propose an efficient stochastic method to estimate those parameters. Finally, we propose a practical means of estimating the average amount of cumulative radiation damage as a function of radiation dose and spatial frequency, and a robust method of fitting relative B-factors to it. We evaluate our method on three publicly available datasets, and illustrate its usefulness by comparison with state-of-the-art methods and previously published results. The new method has been implemented as Bayesian polishing in RELION-3, where it replaces the existing particle polishing method, as it outperforms the latter in all tests conducted.

Subfields: Statistics and Probability, Structural Biology, Surfaces, Coatings and Films

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Citations in the corpus

The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands (2022, positive): “The best 3D class contained 692,833 particles, which were rescaled to 1.068 Å/pix and subjected to 3D refinement, Ctfrefine and Byaesian polishing, following a final 3D refinement (Zivanov et al., 2018; Zivanov et al., 2019).”
New tools for automated high-resolution cryo-EM structure determination in RELION-3 (2018, methodology): “More details about the Bayesian polishing and our implementation of the MotionCor2 algorithm have been described by Zivanov et al, (2018) .”
Cryo-EM structure of the SARS-CoV-2 3a ion channel in lipid nanodiscs (2020, background): “72 e- Å2 in the first set (1-2007) and second set (2008-6309) of movies respectively.”
Comprehensive phylogenetic analysis of the ribonucleotide reductase family reveals an ancestral clade (2022, positive): “Bayesian polishing (Zivanov et al., 2019) training and polishing jobs were then performed with this post-processing job as input.”
Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein (2020, methodology): “3D refinements were carried out using non-uniform refinement along with per-particle defocus refinement in cryoSPARC (Punjani et al., 2017) using an ab initio model generated using cryoSPARC. Particle images were subjected to Bayesian polishing (Zivanov et al., 2019) before performing another round ”
Structure of the decoy module of human glycoprotein 2 and uromodulin and its interaction with bacterial adhesin FimH (2022, methodology): “Third, the top AlphaFold2 model and P 2 1 2 1 2 1 / C 2-structure derived homology models (r.m.s.d. 0.7/0.8 Å) of D10C were individually rigidly docked with UCSF Chimera into the 3D reconstruction of full-length UMOD (overall nominal resolution 4.7 Å) 6 , whose masking and postprocessing with RELION”
Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology (2020, positive): “Particle images were subjected to Bayesian polishing using Relion (Zivanov et al., 2018; Zivanov et al., 2019) before performing another round of non-uniform reﬁnement in cryoSPARC followed by per-particle defocus reﬁnement and again non-uniform reﬁnement.”
Structure of replicating SARS-CoV-2 polymerase (2020, methodology): “There, all particles were refined in 3D against the reconstruction previously obtained in cryoSPARC, using a mask including only the core part of the polymerase and a short segment of upstream RNA to obtain a 3.1 Å reconstruction.”