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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

Cryo-electron microscopy (cryo-EM) has revolutionized structural biology by enabling near-atomic-level visualization of biomolecular assemblies. However, the exponential growth in cryo-EM data throughput and complexity, coupled with diverse…

Quantitative Methods · Quantitative Biology 2026-02-25 Weining Fu , Kai Shu , Kui Xu , Qiangfeng Cliff Zhang

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

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

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 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

Single particle cryo-electron microscopy is a vital tool for 3D characterization of protein structures. A typical workflow involves acquiring projection images of a collection of randomly oriented particles, picking and classifying…

Image and Video Processing · Electrical Eng. & Systems 2021-03-22 S. V. Venkatakrishnan , Puneet Juneja , Hugh O'Neill

A major challenge in single-particle cryo-electron microscopy (cryo-EM) is that the orientations adopted by the 3D particles prior to imaging are unknown; yet, this knowledge is essential for high-resolution reconstruction. We present a…

Machine Learning · Computer Science 2021-04-14 Jelena Banjac , Laurène Donati , Michaël Defferrard

Cryo-electron microscopy (cryo-EM) is a powerful technique in structural biology and drug discovery, enabling the study of biomolecules at high resolution. Significant advancements by structural biologists using cryo-EM have led to the…

Biomolecules · Quantitative Biology 2024-12-05 Yi Zhou , Yilai Li , Jing Yuan , Quanquan Gu

Cryo-Electron Microscopy (cryo-EM) has become an extremely powerful method for resolving structural details of large biomolecular complexes. However, challenging problems in single-particle methods remain open because of (1) the low…

Biomolecules · Quantitative Biology 2019-08-12 Shengnan Lyu , Christian Wülker , Yuqing Pan , Amitesh S. Jayaraman , Jianhao Zheng , Yilin Cai , Gregory S. Chirikjian

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) 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

We address recovery of the three-dimensional backbone structure of single polypeptide proteins from single-particle cryo-electron microscopy (Cryo-SPA) data. Cryo-SPA produces noisy tomographic projections of electrostatic potentials of…

Biomolecules · Quantitative Biology 2024-10-02 Erik Jansson , Jonathan Krook , Klas Modin , Ozan Öktem

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

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…

Single-Particle Reconstruction (SPR) in Cryo-Electron Microscopy (cryo-EM) is the task of estimating the 3D structure of a molecule from a set of noisy 2D projections, taken from unknown viewing directions. Many algorithms for SPR start…

Optimization and Control · Mathematics 2018-01-09 Eitan Levin , Tamir Bendory , Nicolas Boumal , Joe Kileel , 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

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

Cryo-EM is a vital technique for determining 3D structure of biological molecules such as proteins and viruses. The cryo-EM reconstruction problem is challenging due to the high noise levels, the missing poses of particles, and the…

Quantitative Methods · Quantitative Biology 2024-06-05 Larissa de Ruijter , Gabriele Cesa