Orthogonal Matrix Retrieval in Cryo-Electron Microscopy

TL;DR

This paper introduces two novel methods, Orthogonal Extension and Orthogonal Replacement, for recovering missing orthogonal matrices in cryo-EM 3D structure determination, adapting phase retrieval techniques from X-ray crystallography.

Contribution

The paper develops and demonstrates two new algorithms for orthogonal matrix retrieval in cryo-EM, enhancing 3D reconstruction accuracy from 2D images.

Findings

Successful numerical experiments on simulated data validate the methods.

The approaches effectively recover orthogonal matrices in cryo-EM reconstructions.

Abstract

In single particle reconstruction (SPR) from cryo-electron microscopy (cryo-EM), the 3D structure of a molecule needs to be determined from its 2D projection images taken at unknown viewing directions. Zvi Kam showed already in 1980 that the autocorrelation function of the 3D molecule over the rotation group SO(3) can be estimated from 2D projection images whose viewing directions are uniformly distributed over the sphere. The autocorrelation function determines the expansion coefficients of the 3D molecule in spherical harmonics up to an orthogonal matrix of size $(2l+1)\times (2l+1)$ for each $l=0,1,2,...$. In this paper we show how techniques for solving the phase retrieval problem in X-ray crystallography can be modified for the cryo-EM setup for retrieving the missing orthogonal matrices. Specifically, we present two new approaches that we term Orthogonal Extension and Orthogonal Replacement, in which the main algorithmic components are the singular value decomposition and semidefinite programming. We demonstrate the utility of these approaches through numerical experiments on simulated data.