A Bayesian approach for suppression of limited angular sampling artifacts in single particle 3D reconstruction

Toshio Moriya, Erman Acar, R. Holland Cheng, Ulla Ruotsalainen

    Research output: Contribution to journalArticleScientificpeer-review

    6 Citations (Scopus)

    Abstract

    In the single particle reconstruction, the initial 3D structure often suffers from the limited angular sampling artifact. Selecting 2D class averages of particle images generally improves the accuracy and efficiency of the reference-free 3D angle estimation, but causes an insufficient angular sampling to fill the information of the target object in the 3D frequency space. Similarly, the initial 3D structure by the random-conical tilt reconstruction has the well-known "missing cone" artifact. Here, we attempted to solve the limited angular sampling problem by sequentially applying maximum a posteriori estimate with expectation maximization algorithm (sMAP-EM). Using both simulated and experimental cryo-electron microscope images, the sMAP-EM was compared to the direct Fourier method on the basis of reconstruction error and resolution. To establish selection criteria of the final regularization weight for the sMAP-EM, the effects of noise level and sampling sparseness on the reconstructions were examined with evenly distributed sampling simulations. The frequency information filled in the missing cone of the conical tilt sampling simulations was assessed by developing new quantitative measurements. All the results of visual and numerical evaluations showed the sMAP-EM performed better than the direct Fourier method, regardless of the sampling method, noise level, and sampling sparseness. Furthermore, the frequency domain analysis demonstrated that the sMAP-EM can fill the meaningful information in the unmeasured angular space without detailed a priori knowledge of the objects. The current research demonstrated that the sMAP-EM has a high potential to facilitate the determination of 3D protein structures at near atomic-resolution.

    Original languageEnglish
    Pages (from-to)318–331
    Number of pages14
    JournalJournal of Structural Biology
    Volume191
    Issue number3
    DOIs
    Publication statusPublished - 3 Apr 2015
    Publication typeA1 Journal article-refereed

    Keywords

    • Cryo-electron microscopy
    • Maximum a posteriori probability estimation
    • Median root prior reconstruction
    • Missing cone
    • Poisson image formation model
    • Sparse angular sampling

    Publication forum classification

    • Publication forum level 1

    ASJC Scopus subject areas

    • Structural Biology

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