title: Likelihood-based classification of cryo-EM images using FREALIGN.
abstract: We describe an implementation of maximum likelihood classification for single particle electron cryo-microscopy that is based on the FREALIGN software. Particle alignment parameters are determined by maximizing a joint likelihood that can include hierarchical priors, while classification is performed by expectation maximization of a marginal likelihood. We test the FREALIGN implementation using a simulated dataset containing computer-generated projection images of three different 70S ribosome structures, as well as a publicly available dataset of 70S ribosomes. The results show that the mixed strategy of the new FREALIGN algorithm yields performance on par with other maximum likelihood implementations, while remaining computationally efficient.
authors.affiliation: National Resource for Automated Molecular Microscopy, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Lyumkis
authors.affiliation: Department of Biochemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, MS029, 415 South Street, Waltham, MA 02454, USA.
authors.forename: Axel F
authors.initials: AF
authors.lastname: Brilot
authors.affiliation: Department of Biochemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, MS029, 415 South Street, Waltham, MA 02454, USA.
authors.forename: Douglas L
authors.initials: DL
authors.lastname: Theobald
authors.affiliation: Department of Biochemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, MS029, 415 South Street, Waltham, MA 02454, USA; Howard Hughes Medical Institute, Brandeis University, MS029, 415 South Street, Waltham, MA 02454, USA. Electronic address: niko@grigorieff.org.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Grigorieff
mesh_terms: D000465:Algorithms; D001499:Bayes Theorem; D003198:Computer Simulation; D020285:Cryoelectron Microscopy / Q000379:methods; D004926:Escherichia coli; D007091:Image Processing, Computer-Assisted; D016013:Likelihood Functions; D008958:Models, Molecular; D054681:Ribosome Subunits, Large, Bacterial / Q000648:ultrastructure; D054680:Ribosome Subunits, Small, Bacterial / Q000648:ultrastructure; D012984:Software
keywords: Classification; Electron microscopy; Maximum likelihood; Protein structure; Single particle