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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 tomography (cryo-ET) has emerged as a powerful tool for studying the structural heterogeneity of proteins and their complexes, offering insights into macromolecular dynamics directly within cells. Driven by recent…

Biomolecules · Quantitative Biology 2025-07-01 Jackson Carrion , Joseph H. Davis

Cryo-electron microscopy (cryo-EM) is a technique for reconstructing the 3-dimensional (3D) structure of biomolecules (especially large protein complexes and molecular assemblies). As the resolution increases to the near-atomic scale,…

Computer Vision and Pattern Recognition · Computer Science 2023-08-08 Weijie Chen , Xinyan Wang , Yuhang Wang

Cryogenic electron microscopy (cryo-EM) has become an enabling technology in drug discovery and in understanding molecular bases of disease by producing near-atomic resolution (less than 0.4 nm) 3D reconstructions of biological…

Computer Vision and Pattern Recognition · Computer Science 2020-07-23 Hong Xu , David E. Timm , Shireen Y. Elhabian

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

Cellular Electron Cryo-Tomography (CECT) is a powerful imaging technique for the 3D visualization of cellular structure and organization at submolecular resolution. It enables analyzing the native structures of macromolecular complexes and…

Quantitative Methods · Quantitative Biology 2018-05-16 Chang Liu , Xiangrui Zeng , Ruogu Lin , Xiaodan Liang , Zachary Freyberg , Eric Xing , Min Xu

Cryo-electron microscopy (cryo-EM) emerges as a pivotal technology for determining the architecture of cells, viruses, and protein assemblies at near-atomic resolution. Traditional particle picking, a key step in cryo-EM, struggles with…

Biomolecules · Quantitative Biology 2024-04-17 Chentianye Xu , Xueying Zhan , Min Xu

Single-particle cryo-electron microscopy (cryo-EM) is an emerging imaging modality capable of visualizing proteins and macro-molecular complexes at near-atomic resolution. The low electron-doses used to prevent sample radiation damage,…

Image and Video Processing · Electrical Eng. & Systems 2020-11-24 Qinwen Huang , Ye Zhou , Xiaochen Du , Reed Chen , Jianyou Wang , Cynthia Rudin , Alberto Bartesaghi

Cryo-EM reconstruction algorithms seek to determine a molecule's 3D density map from a series of noisy, unlabeled 2D projection images captured with an electron microscope. Although reconstruction algorithms typically model the 3D volume as…

Biomolecules · Quantitative Biology 2021-07-06 Ellen D. Zhong , Adam Lerer , Joseph H. Davis , Bonnie Berger

Cryogenic electron microscopy (cryo-EM) provides images from different copies of the same biomolecule in arbitrary orientations. Here, we present an end-to-end unsupervised approach that learns individual particle orientations from cryo-EM…

Image and Video Processing · Electrical Eng. & Systems 2021-07-08 Youssef S. G. Nashed , Frederic Poitevin , Harshit Gupta , Geoffrey Woollard , Michael Kagan , Chuck Yoon , Daniel Ratner

Single-particle cryo-electron microscopy (cryo-EM) has become a cornerstone of structural biology, enabling near-atomic resolution analysis of macromolecules through advanced computational methods. However, the development of cryo-EM…

Computer Vision and Pattern Recognition · Computer Science 2025-10-07 Runmin Jiang , Genpei Zhang , Yuntian Yang , Siqi Wu , Minhao Wu , Wanyue Feng , Yizhou Zhao , Xi Xiao , Xiao Wang , Tianyang Wang , Xingjian Li , Muyuan Chen , Min Xu

Cryo-EM data processing typically focuses on the structure of the main conformational state under investigation and discards images that belong to other states. This approach can reach atomic resolution, but ignores vast amounts of valuable…

Biomolecules · Quantitative Biology 2024-02-20 Felix Lambrecht , Andreas Kröpelin , Mario Lüttich , Michael Habeck , David Haselbach , Holger Stark

Single-particle cryo-electron microscopy (cryo-EM) reconstructs the three-dimensional (3D) structure of bio-molecules from a large set of 2D projection images with random and unknown orientations. A crucial step in the single-particle…

Image and Video Processing · Electrical Eng. & Systems 2020-06-24 Mona Zehni , Laurène Donati , Emmanuel Soubies , Zhizhen J. Zhao , Michael Unser

Single particle cryo-electron microscopy has become a critical tool in structural biology over the last decade, able to achieve atomic scale resolution in three dimensional models from hundreds of thousands of (noisy) two-dimensional…

Numerical Analysis · Mathematics 2023-07-19 Aaditya V. Rangan , Leslie Greengard

Many imaging modalities involve reconstruction of unknown objects from collections of noisy projections related by random rotations. In one of these modalities, cryogenic electron microscopy (cryo-EM), the extremely low signal-to-noise…

Image and Video Processing · Electrical Eng. & Systems 2025-10-16 Joakim Andén , Justus Sagemüller

High-resolution structure determination by cryo-electron microscopy (cryo-EM) requires the accurate fitting of an atomic model into an experimental density map. Traditional refinement pipelines such as Phenix.real_space_refine and Rosetta…

Biomolecules · Quantitative Biology 2026-03-10 Fuyao Huang , Xiaozhu Yu , Kui Xu , Qiangfeng Cliff Zhang

Cryo-electron microscopy (cryo-EM) has recently emerged as a powerful tool for obtaining three-dimensional (3D) structures of biological macromolecules in native states. A minimum cryo-EM image data set for deriving a meaningful…

Applications · Statistics 2014-04-28 Ting-Li Chen , Dai-Ni Hsieh , Hung Hung , I-Ping Tu , Pei-Shien Wu , Yi-Ming Wu , Wei-Hau Chang , Su-Yun Huang

Cryo-electron microscopy (cryo-EM) has achieved near-atomic level resolution of biomolecules by reconstructing 2D micrographs. However, the resolution and accuracy of the reconstructed particles are significantly reduced due to the…

Computer Vision and Pattern Recognition · Computer Science 2024-01-03 Jing Zhang , Tengfei Zhao , ShiYu Hu , Xin Zhao

Cryogenic electron microscopy (Cryo-EM) has become an essential tool for capturing high-resolution biological structures. Despite its advantage in visualizations, the large storage size of Cryo-EM data file poses significant challenges for…

Machine Learning · Computer Science 2025-12-16 Chunyu Zou

Cryo-electron tomography (Cryo-ET) is a 3D imaging technique that enables the systemic study of shape, abundance, and distribution of macromolecular structures in single cells in near-atomic resolution. However, the systematic and efficient…

Biomolecules · Quantitative Biology 2021-06-29 Kai Yi , Jianye Pang , Yungeng Zhang , Xiangrui Zeng , Min Xu