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In cryo-electron microscopy (cryo-EM), a microscope generates a top view of a sample of randomly-oriented copies of a molecule. The problem of single particle reconstruction (SPR) from cryo-EM is to use the resulting set of noisy 2D…

Numerical Analysis · Mathematics 2014-09-16 Gene Katsevich , Alexander Katsevich , Amit Singer

A single-particle cryo-electron microscopy (cryo-EM) measurement, called a micrograph, consists of multiple two-dimensional tomographic projections of a three-dimensional (3-D) molecular structure at unknown locations, taken under unknown…

Image and Video Processing · Electrical Eng. & Systems 2026-03-10 Shay Kreymer , Amit Singer , Tamir Bendory

Single-particle cryo-EM has transformed structural biology but still faces challenges in resolving conformational heterogeneity at atomic resolution. Existing cryo-EM heterogeneity analysis methods either lack atomic details or tend to…

Biomolecules · Quantitative Biology 2025-10-21 Chengwei Zhang , Shimian Li , Yihao Niu , Zhen Zhu , Sihao Yuan , Sirui Liu , Yi Qin Gao

Background: Single-particle cryo-electron microscopy (cryo-EM) has become a popular tool for structural determination of biological macromolecular complexes. High-resolution cryo-EM reconstruction often requires hundreds of thousands of…

Data Analysis, Statistics and Probability · Physics 2017-09-05 Yanan Zhu , Qi Ouyang , Youdong Mao

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

A major challenge in single particle reconstruction from cryo-electron microscopy is to establish a reliable ab-initio three-dimensional model using two-dimensional projection images with unknown orientations. Common-lines based methods…

Machine Learning · Computer Science 2013-04-11 Lanhui Wang , Amit Singer , Zaiwen Wen

Cryo-electron microscopy (cryo-EM) is a widely used technique for recovering the 3-D structure of biological molecules from a large number of experimentally generated noisy 2-D tomographic projection images of the 3-D structure, taken from…

Numerical Analysis · Mathematics 2025-11-17 Jeremy Hoskins , Yuehaw Khoo , Oscar Mickelin , Amit Singer , Yuguan Wang

Cryo-electron microscopy (cryo-EM) has become a tool of fundamental importance in structural biology, helping us understand the basic building blocks of life. The algorithmic challenge of cryo-EM is to jointly estimate the unknown 3D poses…

Computer Vision and Pattern Recognition · Computer Science 2022-09-01 Axel Levy , Frédéric Poitevin , Julien Martel , Youssef Nashed , Ariana Peck , Nina Miolane , Daniel Ratner , Mike Dunne , Gordon Wetzstein

In single particle reconstruction (SPR) from cryo-electron microscopy (cryo-EM), the 3D structure of a molecule needs to be determined from its 2D projection images taken at unknown viewing directions. Zvi Kam showed already in 1980 that…

Computer Vision and Pattern Recognition · Computer Science 2016-02-24 Tejal Bhamre , Teng Zhang , Amit Singer

We propose a method to reconstruct the 3-D molecular structure from micrographs collected at just one sample tilt angle in the random conical tilt scheme in cryo-electron microscopy. Our method uses autocorrelation analysis on the…

Data Analysis, Statistics and Probability · Physics 2021-01-12 Ti-Yen Lan , Nicolas Boumal , Amit Singer

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

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

Cryo-Electron Microscopy (cryo-EM) has emerged as a key technology to determine the structure of proteins, particularly large protein complexes and assemblies in recent years. A key challenge in cryo-EM data analysis is to automatically…

Biomolecules · Quantitative Biology 2023-04-04 Nabin Giri , Raj S. Roy , Jianlin Cheng

The single-particle cryo-EM field faces the persistent challenge of preferred orientation, lacking general computational solutions. We introduce cryoPROS, an AI-based approach designed to address the above issue. By generating the auxiliary…

Biomolecules · Quantitative Biology 2023-09-27 Hui Zhang , Dihan Zheng , Qiurong Wu , Nieng Yan , Zuoqiang Shi , Mingxu Hu , Chenglong Bao

Cryogenic electron microscopy (cryo-EM) is an invaluable technique for determining high-resolution three-dimensional structures of biological macromolecules using transmission particle images. The inherent symmetry in these macromolecules…

Optimization and Control · Mathematics 2024-11-06 Qi Zhang , Chenglong Bao , Hai Lin , Mingxu Hu

Cryo-electron microscopy is a revolutionary technique that can provide 3D density maps at near-atomic resolution. However, map validation is still an open issue in the field. Despite several efforts from the community, it is possible to…

Biological Physics · Physics 2019-08-06 Sebastian Ortiz , Luka Stanisic , Boris A Rodriguez , Markus Rampp , Gerhard Hummer , Pilar Cossio

Differentiating signals from the background in micrographs is a critical initial step for cryogenic electron microscopy (cryo-EM), yet it remains laborious due to low signal-to-noise ratio (SNR), the presence of contaminants and densely…

Image and Video Processing · Electrical Eng. & Systems 2025-09-30 Szu-Chi Chung , Po-Cheng Chou

Single particle reconstruction has recently emerged in 3D fluorescence microscopy as a powerful technique to improve the axial resolution and the degree of fluorescent labeling. It is based on the reconstruction of an average volume of a…

Image and Video Processing · Electrical Eng. & Systems 2023-01-24 Thibaut Eloy , Etienne Baudrier , Marine Laporte , Virginie Hamel , Paul Guichard , Denis Fortun

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

The central problem in cryo-electron microscopy (cryo-EM) is to recover the 3D structure from noisy 2D projection images which requires estimating the missing projection angles (poses). Recent methods attempted to solve the 3D…

Computer Vision and Pattern Recognition · Computer Science 2023-02-15 Lin Yao , Ruihan Xu , Zhifeng Gao , Guolin Ke , Yuhang Wang