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PMID: 23872434 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Likelihood-based classification of cryo-EM images using FREALIGN.

Journal of structural biology ·Vol. 183 ·No. 3 ·2013-09-00 ·Pages 377-388

Lyumkis D, Brilot AF, Theobald DL, Grigorieff N

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.

Keywords
Classification Electron microscopy Maximum likelihood Protein structure Single particle
MeSH Terms
Algorithms Bayes Theorem Computer Simulation Cryoelectron Microscopy/methods Escherichia coli Image Processing, Computer-Assisted Likelihood Functions Models, Molecular Ribosome Subunits, Large, Bacterial/ultrastructure Ribosome Subunits, Small, Bacterial/ultrastructure Software
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lyumkis Dmitry
National Resource for Automated Molecular Microscopy, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Brilot Axel F
Department of Biochemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, MS029, 415 South Street, Waltham, MA 02454, USA.
Theobald Douglas L
Department of Biochemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, MS029, 415 South Street, Waltham, MA 02454, USA.
Grigorieff Nikolaus
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.
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Article Info
Journal
Journal of structural biology
Abbr.
J Struct Biol
ISSN
1095-8657
Published
2013-09-00
Epub
2013-00-17
Pages
377-388
Language
English
Region
United States
NLM ID
9011206
PMCID
PMC3824613
Subset
IM
Grants
NIGMS NIH HHS · P01 GM062580 · United States
NIGMS NIH HHS · P01 GM62580 · United States
NIGMS NIH HHS · P41 GM103310 · United States
Howard Hughes Medical Institute · United States
NIGMS NIH HHS · R01 GM096053 · United States
NIGMS NIH HHS · R01 GM094468 · United States
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