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In recent years, an abundance of new molecular structures have been elucidated using cryo-electron microscopy (cryo-EM), largely due to advances in hardware technology and data processing techniques. Owing to these new exciting…

Information Theory · Computer Science 2020-04-22 Tamir Bendory , Alberto Bartesaghi , Amit Singer

In this report we study the problem of determining three-dimensional orientations for noisy projections of randomly oriented identical particles. The problem is of central importance in the tomographic reconstruction of the density map of…

Data Structures and Algorithms · Computer Science 2007-05-23 Taneli Mielikäinen , Janne Ravantti , Esko Ukkonen

In single-particle cryo-electron microscopy (cryo-EM), the efficient determination of orientation parameters for 2D projection images poses a significant challenge yet is crucial for reconstructing 3D structures. This task is complicated by…

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

Cryogenic electron microscopy (cryo-EM) provides a unique opportunity to study the structural heterogeneity of biomolecules. Being able to explain this heterogeneity with atomic models would help our understanding of their functional…

One of the difficulties in 3D reconstruction of molecules from images in single particle Cryo-Electron Microscopy (Cryo-EM), in addition to high levels of noise and unknown image orientations, is heterogeneity in samples: in many cases, the…

Computer Vision and Pattern Recognition · Computer Science 2016-07-13 Roy R. Lederman , Amit Singer

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

We target the problem of estimating the center of mass of noisy 2-D images. We assume that the noise dominates the image, and thus many standard approaches are vulnerable to estimation errors. Our approach uses a surrogate function to the…

Image and Video Processing · Electrical Eng. & Systems 2021-03-04 Ayelet Heimowitz , Nir Sharon , Amit Singer

The number of noisy images required for molecular reconstruction in single-particle cryo-electron microscopy (cryo-EM) is governed by the autocorrelations of the observed, randomly-oriented, noisy projection images. In this work, we…

Numerical Analysis · Mathematics 2023-05-03 Tamir Bendory , Yuehaw Khoo , Joe Kileel , Oscar Mickelin , 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

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

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

Cryo-EM is a transformational paradigm in molecular biology where computational methods are used to infer 3D molecular structure at atomic resolution from extremely noisy 2D electron microscope images. At the forefront of research is how to…

Quantitative Methods · Quantitative Biology 2025-06-12 Shayan Shekarforoush , David B. Lindell , Marcus A. Brubaker , David J. Fleet

Understanding protein flexibility and its dynamic interactions with other molecules is essential for studying protein function. Although cryogenic electron microscopy(cryo-EM) provides an opportunity to observe macromolecular dynamics…

Computer Vision and Pattern Recognition · Computer Science 2026-02-03 Bintao He , Yiran Cheng , Hongjia Li , Xiang Gao , Xin Gao , Fa Zhang , Renmin Han

Cryo-electron microscopy (cryo-EM) has become a major experimental technique to determine the structures of large protein complexes and molecular assemblies, as evidenced by the 2017 Nobel Prize. Although cryo-EM has been drastically…

Biomolecules · Quantitative Biology 2021-06-01 Dong Si , Andrew Nakamura , Runbang Tang , Haowen Guan , Jie Hou , Ammaar Firozi , Renzhi Cao , Kyle Hippe , Minglei Zhao

The computational pipelines of single-particle cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET) include an early particle-picking stage, in which a micrograph or tomogram is scanned to extract candidate particles,…

Signal Processing · Electrical Eng. & Systems 2026-04-14 Amnon Balanov , Alon Zabatani , Tamir Bendory

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

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

In the past decade, deep conditional generative models have revolutionized the generation of realistic images, extending their application from entertainment to scientific domains. Single-particle cryo-electron microscopy (cryo-EM) is…

Computer Vision and Pattern Recognition · Computer Science 2024-10-01 Jiakai Zhang , Qihe Chen , Yan Zeng , Wenyuan Gao , Xuming He , Zhijie Liu , Jingyi Yu

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

Simulation-based inference provides a powerful framework for cryo-electron microscopy, employing neural networks in methods like CryoSBI to infer biomolecular conformations via learned latent representations. This latent space represents a…

Quantitative Methods · Quantitative Biology 2025-09-05 Luke Evans , Octavian-Vlad Murad , Lars Dingeldein , Pilar Cossio , Roberto Covino , Marina Meila