A Two-Phase Improved Correlation Method for Automatic Particle Selection in Cryo-EM.

Particle selection from cryo-electron microscopy (Cryo-EM) images is very important for high-resolution reconstruction of macromolecular structure. The methods of particle selection can be roughly grouped into two classes, template-matching methods and feature-based methods. In general, template-matching methods usually generate better results than feature-based methods. However, the accuracy of template-matching methods is restricted by the noise and low contrast of Cryo-EM images. Moreover, the processing speed of template-matching methods, restricted by the random orientation of particles, further limits their practical applications. In this paper, combining the advantages of feature-based methods and template-matching methods, we present a two-phase improved correlation method for automatic, fast particle selection. In Phase I, we generate a preliminary particle set using rotation-invariant features of particles. In Phase II, we filter the preliminary particle set using a correlation method to reduce the interference of the high noise background and improve the precision of particle selection. We apply several optimization strategies, including a modified adaboost algorithm, Divide and Conquer technique, cascade strategy and graphics processing unit parallel technique, to improve feature recognition ability and reduce processing time. In addition, we developed two correlation score functions for different correlation situations. Experimental results on the benchmark of Cryo-EM images show that our method can improve the accuracy and processing speed of particle selection significantly.