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Single particle cryo-electron microscopy (EM) is an increasingly popular method for determining the 3-D structure of macromolecules from noisy 2-D images of single macromolecules whose orientations and positions are random and unknown. One…

Computer Vision and Pattern Recognition · Computer Science 2017-04-11 Roy R. Lederman , Amit Singer

We consider the problem of joint estimation of structured covariance matrices. Assuming the structure is unknown, estimation is achieved using heterogeneous training sets. Namely, given groups of measurements coming from centered…

Statistics Theory · Mathematics 2016-04-20 Ilya Soloveychik , Ami Wiesel

Cryo-electron microscopy (cryo-EM) is an emerging experimental method to characterize the structure of large biomolecular assemblies. Single particle cryo-EM records 2D images (so-called micrographs) of projections of the three-dimensional…

Applications · Statistics 2013-12-02 Mikhail Langovoy , Michael Habeck , Bernhard Schoelkopf

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 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

Cryo-electron microscopy (cryo-EM) is a powerful technique for determining the structure of proteins and other macromolecular complexes at near-atomic resolution. In single particle cryo-EM, the central problem is to reconstruct the…

Quantitative Methods · Quantitative Biology 2020-02-18 Ellen D. Zhong , Tristan Bepler , Joseph H. Davis , Bonnie Berger

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

Enhancing cryogenic electron microscopy (cryo-EM) 3D density maps at intermediate resolution (4-8 {\AA}) is crucial in protein structure determination. Recent advances in deep learning have led to the development of automated approaches for…

Computer Vision and Pattern Recognition · Computer Science 2025-05-16 Chenwei Zhang , Khanh Dao Duc

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

Constructing of molecular structural models from Cryo-Electron Microscopy (Cryo-EM) density volumes is the critical last step of structure determination by Cryo-EM technologies. Methods have evolved from manual construction by structural…

Machine Learning · Computer Science 2019-02-13 Kui Xu , Zhe Wang , Jiangping Shi , Hongsheng Li , Qiangfeng Cliff Zhang

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

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 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…

Cryo-electron microscopy (cryo-EM) has recently become a premier method for obtaining high-resolution structures of biological macromolecules. However, it is limited to biomolecular samples with low conformational heterogeneity, where all…

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

In this paper we study the formal algebraic structure underlying the intrinsic classification algorithm, recently introduced by Hadani, Shkolnisky, Singer and Zhao, for classifying noisy projection images of similar viewing directions in…

Representation Theory · Mathematics 2011-04-07 Ronny Hadani , Amit Singer

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

Structural flexibility and/or dynamic interactions with other molecules is a critical aspect of protein function. CryoEM provides direct visualization of individual macromolecules sampling different conformational and compositional states.…

Biomolecules · Quantitative Biology 2021-08-04 Muyuan Chen , Steven Ludtke

Single particle electron cryomicroscopy (cryo-EM) allows for structures of proteins and protein complexes to be determined from images of non-crystalline specimens. Cryo-EM data analysis requires electron microscope images of randomly…

Instrumentation and Detectors · Physics 2015-11-23 Jianhua Zhao , Marcus A. Brubaker , Samir Benlekbir , John L. Rubinstein

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