Pre-pro is a fast pre-processor for single-particle cryo-EM by enhancing 2D classification

Commun Biol. 2020 Sep 11;3(1):508. doi: 10.1038/s42003-020-01229-0.

Abstract

2D classification plays a pivotal role in analyzing single particle cryo-electron microscopy images. Here, we introduce a simple and loss-less pre-processor that incorporates a fast dimension-reduction (2SDR) de-noiser to enhance 2D classification. By implementing this 2SDR pre-processor prior to a representative classification algorithm like RELION and ISAC, we compare the performances with and without the pre-processor. Tests on multiple cryo-EM experimental datasets show the pre-processor can make classification faster, improve yield of good particles and increase the number of class-average images to generate better initial models. Testing on the nanodisc-embedded TRPV1 dataset with high heterogeneity using a 3D reconstruction workflow with an initial model from class-average images highlights the pre-processor improves the final resolution to 2.82 Å, close to 0.9 Nyquist. Those findings and analyses suggest the 2SDR pre-processor, of minimal cost, is widely applicable for boosting 2D classification, while its generalization to accommodate neural network de-noisers is envisioned.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Cryoelectron Microscopy / methods*
  • Humans
  • Image Processing, Computer-Assisted / methods*
  • Imaging, Three-Dimensional / methods
  • Neural Networks, Computer
  • Protein Conformation
  • Single Molecule Imaging / methods*
  • TRPV Cation Channels / chemistry
  • TRPV Cation Channels / ultrastructure

Substances

  • TRPV Cation Channels
  • TRPV1 protein, human