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Cryo-electron microscopy (cryo-EM) is an imaging modality that provides unique insights into the dynamics of proteins and other building blocks of life. The algorithmic challenge of jointly estimating the poses, 3D structure, and…

Computer Vision and Pattern Recognition · Computer Science 2022-10-17 Axel Levy , Gordon Wetzstein , Julien Martel , Frederic Poitevin , Ellen D. Zhong

The goal of cryo-electron microscopy (EM) is to reconstruct the 3-dimensional structure of a molecule from a collection of its 2-dimensional projected images. In this article, we show that the basic premise of cryo-EM --- patching together…

Computer Vision and Pattern Recognition · Computer Science 2017-04-25 Ke Ye , Lek-Heng Lim

Single-particle cryo-electron microscopy (cryo-EM) has become one of the mainstream structural biology techniques because of its ability to determine high-resolution structures of dynamic bio-molecules. However, cryo-EM data acquisition…

Machine Learning · Computer Science 2022-04-18 Quanfu Fan , Yilai Li , Yuguang Yao , John Cohn , Sijia Liu , Seychelle M. Vos , Michael A. Cianfrocco

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

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

Thanks to automated cryo-EM and GPU-accelerated processing, single-particle cryo-EM has become a rapid structure determination method that permits capture of dynamical structures of molecules in solution, which has been recently…

Quantitative Methods · Quantitative Biology 2025-09-30 Szu-Chi Chung , Cheng-Yu Hung , Huei-Lun Siao , Hung-Yi Wu , Wei-Hau Chang , I-Ping Tu

We consider the problem of estimating a signal from noisy circularly-translated versions of itself, called multireference alignment (MRA). One natural approach to MRA could be to estimate the shifts of the observations first, and infer the…

Information Theory · Computer Science 2018-02-14 Tamir Bendory , Nicolas Boumal , Chao Ma , Zhizhen Zhao , Amit Singer

Macromolecules change their shape (conformation) in the process of carrying out their functions. The imaging by cryo-electron microscopy of rapidly-frozen, individual copies of macromolecules (single particles) is a powerful and general…

Biomolecules · Quantitative Biology 2022-11-22 Bogdan Toader , Fred J. Sigworth , Roy R. Lederman

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 (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 microscopy (cryo-EM) has emerged as a powerful technique for resolving the three-dimensional structures of macromolecules. A key challenge in cryo-EM is characterizing continuous heterogeneity, where molecules adopt a…

Machine Learning · Statistics 2026-02-20 Roey Yadgar , Roy R. Lederman , Yoel Shkolnisky

We consider the problem of recovering the three-dimensional atomic structure of a flexible macromolecule from a heterogeneous cryo-EM dataset. The dataset contains noisy tomographic projections of the electrostatic potential of the…

Image and Video Processing · Electrical Eng. & Systems 2023-02-08 Carlos Esteve-Yagüe , Willem Diepeveen , Ozan Öktem , Carola-Bibiane Schönlieb

Protein structure prediction models are now capable of generating accurate 3D structural hypotheses from sequence alone. However, they routinely fail to capture the conformational diversity of dynamic biomolecular complexes, often requiring…

Machine Learning · Computer Science 2025-12-02 Rishwanth Raghu , Axel Levy , Gordon Wetzstein , Ellen D. Zhong

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) 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…

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

Motivated by the structure reconstruction problem in single-particle cryo-electron microscopy, we consider the multi-target detection model, where multiple copies of a target signal occur at unknown locations in a long measurement, further…

Information Theory · Computer Science 2020-04-22 Ti-Yen Lan , Tamir Bendory , Nicolas Boumal , Amit Singer

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

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 revisit the topic of common lines between projection images in single particle cryo-electron microscopy (cryo-EM). We derive a novel low-rank constraint on a certain $2n \times n$ matrix storing properly-scaled basis vectors for the…

Optimization and Control · Mathematics 2024-06-10 Tommi Muller , Adriana L. Duncan , Eric J. Verbeke , Joe Kileel