RELION: Implementation of a Bayesian approach to cryo-EM structure determination

TLDR

RELION is an open‑source cryo‑EM refinement program that uses a Bayesian approach to infer model parameters, avoiding the need for user‑tuned alternatives. The paper aims to reduce the computational cost of the MAP algorithm and to provide statistical insights into the accuracy of particle orientation determination. It introduces computational optimizations and a gold‑standard Fourier shell correlation procedure to prevent overfitting. The resulting implementation delivers high‑quality reconstructions and reliable resolution estimates with minimal user intervention at acceptable computational costs.

Abstract

RELION, for REgularized LIkelihood OptimizatioN, is an open-source computer program for the refinement of macromolecular structures by single-particle analysis of electron cryo-microscopy (cryo-EM) data. Whereas alternative approaches often rely on user expertise for the tuning of parameters, RELION uses a Bayesian approach to infer parameters of a statistical model from the data. This paper describes developments that reduce the computational costs of the underlying maximum a posteriori (MAP) algorithm, as well as statistical considerations that yield new insights into the accuracy with which the relative orientations of individual particles may be determined. A so-called gold-standard Fourier shell correlation (FSC) procedure to prevent overfitting is also described. The resulting implementation yields high-quality reconstructions and reliable resolution estimates with minimal user intervention and at acceptable computational costs.