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Cryo-electron microscopy (cryo-EM) is a powerful technique for determining the structure of proteins and other macromolecular complexes at near-atomic resolution. In single particle cryo-EM, the central problem is to reconstruct the…

Quantitative Methods · Quantitative Biology 2020-02-18 Ellen D. Zhong , Tristan Bepler , Joseph H. Davis , Bonnie Berger

Cryo-electron microscopy (Cryo-EM) enables high-resolution imaging of biomolecules, but structural heterogeneity remains a major challenge in 3D reconstruction. Traditional methods assume a discrete set of conformations, limiting their…

Machine Learning · Statistics 2025-09-09 Diego Sanchez Espinosa , Erik H Thiede , Yunan Yang

The cryo-electron microscope (cryo-EM) is increasingly popular these years. It helps to uncover the biological structures and functions of macromolecules. In this paper, we address image denoising problem in cryo-EM. Denoising the cryo-EM…

Computation · Statistics 2018-10-26 Yin Xian , Hanlin Gu , Wei Wang , Xuhui Huang , Yuan Yao , Yang Wang , Jian-Feng Cai

Different tasks in the computational pipeline of single-particle cryo-electron microscopy (cryo-EM) require enhancing the quality of the highly noisy raw images. To this end, we develop an efficient algorithm for signal enhancement of…

Image and Video Processing · Electrical Eng. & Systems 2022-12-06 Guy Sharon , Yoel Shkolnisky , Tamir Bendory

Electron cryo-microscopy (cryo-EM) produces three-dimensional (3D) maps of the electrostatic potential of biological macromolecules, including proteins. Along with knowledge about the imaged molecules, cryo-EM maps allow de novo atomic…

Quantitative Methods · Quantitative Biology 2023-02-09 Kiarash Jamali , Dari Kimanius , Sjors H. W. Scheres

In single-particle cryo-electron microscopy (cryo-EM), K-means clustering algorithm is widely used in unsupervised 2D classification of projection images of biological macromolecules. 3D ab initio reconstruction requires accurate…

Quantitative Methods · Quantitative Biology 2017-01-03 Yaofang Xu , Jiayi Wu , Chang-Cheng Yin , Youdong Mao

Cryo-EM is an increasingly popular method for determining the atomic resolution 3D structure of macromolecular complexes (eg, proteins) from noisy 2D images captured by an electron microscope. The computational task is to reconstruct the 3D…

Computer Vision and Pattern Recognition · Computer Science 2024-10-04 Shayan Shekarforoush , David B. Lindell , Marcus A. Brubaker , David J. Fleet

Single-particle electron cryomicroscopy (cryo-EM) is an increasingly popular technique for elucidating the three-dimensional structure of proteins and other biologically significant complexes at near-atomic resolution. It is an imaging…

Computational Physics · Physics 2020-04-01 Amit Singer , Fred J. Sigworth

Motivated by the task of 2-D classification in single particle reconstruction by cryo-electron microscopy (cryo-EM), we consider the problem of heterogeneous multireference alignment of images. In this problem, the goal is to estimate a…

Image and Video Processing · Electrical Eng. & Systems 2019-10-03 Chao Ma , Tamir Bendory , Nicolas Boumal , Fred Sigworth , Amit Singer

Cryo-electron microscopy (cryo-EM) is an indispensable technique for determining the 3D structures of dynamic biomolecular complexes. While typically applied to image a single molecular species, cryo-EM has the potential for structure…

Computer Vision and Pattern Recognition · Computer Science 2026-03-23 Jeffrey Gu , Minkyu Jeon , Ambri Ma , Serena Yeung-Levy , Ellen D. Zhong

Cryo-electron tomography (cryo-ET) is an imaging technique that allows three-dimensional visualization of macro-molecular assemblies under near-native conditions. Cryo-ET comes with a number of challenges, mainly low signal-to-noise and…

Direct detector device (DDD) cameras have revolutionized single particle electron cryomicroscopy (cryo-EM). In addition to an improved camera detective quantum efficiency, acquisition of DDD movies allows for correction of movement of the…

Quantitative Methods · Quantitative Biology 2015-11-23 John L. Rubinstein , Marcus A. Brubaker

Discovering the 3D atomic structure of molecules such as proteins and viruses is a fundamental research problem in biology and medicine. Electron Cryomicroscopy (Cryo-EM) is a promising vision-based technique for structure estimation which…

Computer Vision and Pattern Recognition · Computer Science 2016-11-18 Marcus A. Brubaker , Ali Punjani , David J. Fleet

Cryo-electron microscopy (cryo-EM) is a powerful imaging technique for reconstructing three-dimensional molecular structures from noisy tomographic projection images of randomly oriented particles. We introduce a new data fusion framework,…

Computer Vision and Pattern Recognition · Computer Science 2025-12-15 Joe Kileel , Oscar Mickelin , Amit Singer , Sheng Xu

Mapping conformational heterogeneity of macromolecules presents a formidable challenge to X-ray crystallography and cryo-electron microscopy, which often presume its absence. This has severely limited our knowledge of the conformations…

Biological Physics · Physics 2015-05-14 P. Schwander , R. Fung , G. N. Phillips , A. Ourmazd

In this paper, we outline the use of Mixture Models in density estimation of large astronomical databases. This method of density estimation has been known in Statistics for some time but has not been implemented because of the large…

Astrophysics · Physics 2007-05-23 A. J. Connolly , C. Genovese , A. W. Moore , R. C. Nichol , J. Schneider , L. Wasserman

Determining the three-dimensional structure of proteins and protein complexes at atomic resolution is a fundamental task in structural biology. Over the last decade, remarkable progress has been made using "single particle" cryo-electron…

Numerical Analysis · Mathematics 2017-06-05 Alex Barnett , Leslie Greengard , Andras Pataki , Marina Spivak

The growing role of data-driven approaches to scientific discovery has unveiled a large class of models that involve latent transformations with a rigid algebraic constraint. Three-dimensional molecule reconstruction in Cryo-Electron…

Information Theory · Computer Science 2019-06-04 Amelia Perry , Jonathan Weed , Afonso S. Bandeira , Philippe Rigollet , Amit Singer

Classifying structural variability in noisy projections of biological macromolecules is a central problem in Cryo-EM. In this work, we build on a previous method for estimating the covariance matrix of the three-dimensional structure…

Computer Vision and Pattern Recognition · Computer Science 2015-12-08 Joakim Andén , Eugene Katsevich , Amit Singer

We present initial results on the use of Mixture Models for density estimation in large astronomical databases. We provide herein both the theoretical and experimental background for using a mixture model of Gaussians based on the…

Astrophysics · Physics 2007-05-23 R. C. Nichol , A. J. Connolly , A. W. Moore , J. Schneider , C. Genovese , L. Wasserman