A particle-filter framework for robust cryo-EM 3D reconstruction

Nat Methods. 2018 Dec;15(12):1083-1089. doi: 10.1038/s41592-018-0223-8. Epub 2018 Nov 30.

Abstract

Single-particle electron cryomicroscopy (cryo-EM) involves estimating a set of parameters for each particle image and reconstructing a 3D density map; robust algorithms with accurate parameter estimation are essential for high resolution and automation. We introduce a particle-filter algorithm for cryo-EM, which provides high-dimensional parameter estimation through a posterior probability density function (PDF) of the parameters given in the model and the experimental image. The framework uses a set of random support points to represent such a PDF and assigns weighting coefficients not only among the parameters of each particle but also among different particles. We implemented the algorithm in a new program named THUNDER, which features self-adaptive parameter adjustment, tolerance to bad particles, and per-particle defocus refinement. We tested the algorithm by using cryo-EM datasets for the cyclic-nucleotide-gated (CNG) channel, the proteasome, β-galactosidase, and an influenza hemagglutinin (HA) trimer, and observed substantial improvement in resolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Cryoelectron Microscopy / methods*
  • Cyclic Nucleotide-Gated Cation Channels / ultrastructure
  • Hemagglutinin Glycoproteins, Influenza Virus / ultrastructure
  • Humans
  • Image Processing, Computer-Assisted / methods*
  • Imaging, Three-Dimensional / methods*
  • Proteasome Endopeptidase Complex / ultrastructure
  • Software*
  • beta-Galactosidase / ultrastructure

Substances

  • Cyclic Nucleotide-Gated Cation Channels
  • Hemagglutinin Glycoproteins, Influenza Virus
  • beta-Galactosidase
  • Proteasome Endopeptidase Complex