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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

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

Determining the 3D structures of biological molecules is a key problem for both biology and medicine. Electron Cryomicroscopy (Cryo-EM) is a promising technique for structure estimation which relies heavily on computational methods to…

Machine Learning · Statistics 2015-01-29 Ali Punjani , Marcus A. Brubaker

Cryo-electron microscopy (cryo-EM), the subject of the 2017 Nobel Prize in Chemistry, is a technology for determining the 3-D structure of macromolecules from many noisy 2-D projections of instances of these macromolecules, whose…

Computer Vision and Pattern Recognition · Computer Science 2020-04-22 Roy R. Lederman , Joakim Andén , Amit Singer

This paper addresses the challenge of classifying polarimetric SAR images by leveraging the peculiar characteristics of the polarimetric covariance matrix (PCM). To this end, a general framework to solve a multiple hypothesis test is…

Signal Processing · Electrical Eng. & Systems 2021-06-22 Pia Addabbo , Filippo Biondi , Carmine Clemente , Sudan Han , Danilo Orlando , Giuseppe Ricci

In cryo-electron microscopy, the 3D electric potentials of an ensemble of molecules are projected along arbitrary viewing directions to yield noisy 2D images. The volume maps representing these potentials typically exhibit a great deal of…

Applications · Statistics 2018-02-08 Joakim Andén , Amit Singer

Cryo-electron microscopy (cryo-EM) has revolutionized experimental protein structure determination. Despite advances in high resolution reconstruction, a majority of cryo-EM experiments provide either a single state of the studied…

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

Single-particle cryo-electron microscopy (cryo-EM) is an emerging imaging modality capable of visualizing proteins and macro-molecular complexes at near-atomic resolution. The low electron-doses used to prevent sample radiation damage,…

Image and Video Processing · Electrical Eng. & Systems 2020-11-24 Qinwen Huang , Ye Zhou , Xiaochen Du , Reed Chen , Jianyou Wang , Cynthia Rudin , Alberto Bartesaghi

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…

Cryo-electron microscopy (cryo-EM) is a powerful technique for determining high-resolution 3D biomolecular structures from imaging data. Its unique ability to capture structural variability has spurred the development of heterogeneous…

Computer Vision and Pattern Recognition · Computer Science 2025-01-17 Minkyu Jeon , Rishwanth Raghu , Miro Astore , Geoffrey Woollard , Ryan Feathers , Alkin Kaz , Sonya M. Hanson , Pilar Cossio , Ellen D. Zhong

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

The field of cryo-electron microscopy has made astounding advancements in the past few years, mainly due to advancements in electron detectors' technology. Yet, one of the key open challenges of the field remains the processing of…

Computer Vision and Pattern Recognition · Computer Science 2019-10-04 Yariv Aizenbud , Yoel Shkolnisky

Single-particle electron cryomicroscopy (cryo-EM) is an increasingly popular technique for elucidating the three-dimensional structure of proteins and other biologically significant complexes at near-atomic resolution. It is an imaging…

Computational Physics · Physics 2020-04-01 Amit Singer , Fred J. Sigworth

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

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

Electron cryomicroscopy (cryo-EM) is an imaging technique widely used in structural biology to determine the three-dimensional structure of biological molecules from noisy two-dimensional projections with unknown orientations. As the…

Numerical Analysis · Mathematics 2025-06-26 Bogdan Toader , Marcus A. Brubaker , Roy R. Lederman

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

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

Factor-based Structural Equation Modeling (SEM) relies on likelihood-based estimation assuming a nonsingular sample covariance matrix, which breaks down in small-sample settings with $p>n$. To address this, we propose a novel estimation…

Machine Learning · Computer Science 2026-04-21 Hiroki Hasegawa , Aoba Tamura , Yukihiko Okada
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