An introduction to maximum-likelihood methods in cryo-EM
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Updated: Jun 8, 2026

Optimizing Sample Preparation for Cryogenic Electron Microscopy
Published on: April 11, 2025
Fred J Sigworth1, Peter C Doerschuk, Jose-Maria Carazo
1Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut, USA.
Abstract:
The maximum-likelihood method provides a powerful approach to many problems in cryo-electron microscopy (cryo-EM) image processing. This contribution aims to provide an accessible introduction to the underlying theory and reviews existing applications in the field. In addition, current developments to reduce computational costs and to improve the statistical description of cryo-EM images are discussed. Combined with the increasing power of modern computers and yet unexplored possibilities provided by theory, these developments are expected to turn the statistical approach into an essential image-processing tool for the electron microscopist.

