Centering Noisy Images with Application to Cryo-EM

SIAM J Imaging Sci. 2021;14(2):689-716. doi: 10.1137/20m1365946. Epub 2021 May 25.

Abstract

We target the problem of estimating the center of mass of objects in noisy two-dimensional images. We assume that the noise dominates the image, and thus many standard approaches are vulnerable to estimation errors, e.g., the direct computation of the center of mass and the geometric median which is a robust alternative to the center of mass. In this paper, we define a novel surrogate function to the center of mass. We present a mathematical and numerical analysis of our method and show that it outperforms existing methods for estimating the center of mass of an object in various realistic scenarios. As a case study, we apply our centering method to data from single-particle cryo-electron microscopy (cryo-EM), where the goal is to reconstruct the three-dimensional structure of macromolecules. We show how to apply our approach for a better translational alignment of molecule images picked from experimental data. In this way, we facilitate the succeeding steps of reconstruction and streamline the entire cryo-EM pipeline, saving computational time and supporting resolution enhancement.

Keywords: alignment; center of mass; centering; cryo-electron microscopy; median of mass; particle picking.