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The determination of molecular orientations is crucial for the three-dimensional reconstruction of Cryo-EM images. Traditionally addressed using the common-line method, this challenge is reformulated as a self-consistency error minimization…

Optimization and Control · Mathematics 2024-11-22 Wanyu Zhang , Ruili Gou , Huikang Liu , Zhiguo Wang , Yinyu Ye

Cryogenic electron microscopy is widely used in structural biology, but its resolution is often limited by the dynamics of the macromolecule. Here, we developed a refinement protocol based on Gaussian mixture models that integrates particle…

Quantitative Methods · Quantitative Biology 2023-08-31 Muyuan Chen , Michael F. Schmid , Wah Chiu

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

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

In this report, we applied expectation and maximization (EM) method described by Philips et al [1] to recover two-dimensional (2D) structure from multiple sparse signal images in random orientation. The detailed derivation of EM algorithm…

Data Analysis, Statistics and Probability · Physics 2017-01-12 Yun Zhao

Cryo-electron microscopy is a revolutionary technique that can provide 3D density maps at near-atomic resolution. However, map validation is still an open issue in the field. Despite several efforts from the community, it is possible to…

Biological Physics · Physics 2019-08-06 Sebastian Ortiz , Luka Stanisic , Boris A Rodriguez , Markus Rampp , Gerhard Hummer , Pilar Cossio

Cryo-electron tomography (Cryo-ET) is a powerful tool in structural biology for 3D visualization of cells and biological systems at resolutions sufficient to identify individual proteins in situ. The measurements are collected by tilting…

Signal Processing · Electrical Eng. & Systems 2025-09-03 Vinith Kishore , Valentin Debarnot , AmirEhsan Khorashadizadeh , Ivan Dokmanić

A main task in cryo-electron microscopy single particle reconstruction is to find a three-dimensional model of a molecule given a set of its randomly oriented and positioned noisy projection-images. In this work, we propose an algorithm for…

Computational Physics · Physics 2022-11-11 Adi Shasha Geva , Yoel Shkolnisky

Principal component analysis (PCA) plays an important role in the analysis of cryo-EM images for various tasks such as classification, denoising, compression, and ab-initio modeling. We introduce a fast method for estimating a compressed…

Numerical Analysis · Mathematics 2022-11-01 Nicholas F. Marshall , Oscar Mickelin , Yunpeng Shi , Amit Singer

X-ray single particle imaging involves the measurement of a large number of noisy diffraction patterns of isolated objects in random orientations. The missing information about these patterns is then computationally recovered in order to…

Image and Video Processing · Electrical Eng. & Systems 2020-05-25 Kartik Ayyer

Recent breakthroughs in high-resolution imaging of biomolecules in solution with cryo-electron microscopy (cryo-EM) have unlocked new doors for the reconstruction of molecular volumes, thereby promising further advances in biology,…

Image and Video Processing · Electrical Eng. & Systems 2022-05-27 Claire Donnat , Axel Levy , Frederic Poitevin , Ellen Zhong , Nina Miolane

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

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

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

Cryogenic electron microscopy (cryo-EM) has become an enabling technology in drug discovery and in understanding molecular bases of disease by producing near-atomic resolution (less than 0.4 nm) 3D reconstructions of biological…

Computer Vision and Pattern Recognition · Computer Science 2020-07-23 Hong Xu , David E. Timm , Shireen Y. Elhabian

Revealing the structure of complex biological macromolecules, such as proteins, is an essential step for understanding the chemical mechanisms that determine the diversity of their functions. Synchrotron based x-ray crystallography and…

Knowledge of a protein's atomic conformational ensemble is critical to determining its function, yet state-of-the-art ensemble prediction models are limited by lack of high-quality conformational data from simulation or experiment. Recent…

Machine Learning · Computer Science 2026-05-12 Jay Shenoy , Miro Astore , Axel Levy , Frédéric Poitevin , Sonya M. Hanson , Gordon Wetzstein

The interaction of a protein with its environment can be understood and controlled via its 3D structure. Experimental methods for protein structure determination, such as X-ray crystallography or cryogenic electron microscopy, shed light on…

Machine Learning · Computer Science 2025-04-24 Axel Levy , Eric R. Chan , Sara Fridovich-Keil , Frédéric Poitevin , Ellen D. Zhong , Gordon Wetzstein

We introduce the EMC algorithm for reconstructing a particle's 3D diffraction intensity from very many photon shot-noise limited 2D measurements, when the particle orientation in each measurement is unknown. The algorithm combines a…

Data Analysis, Statistics and Probability · Physics 2010-03-04 Duane Ne-Te Loh , Veit Elser

We propose a framework to jointly determine the deformation parameters and reconstruct the unknown volume in electron cryotomography (CryoET). CryoET aims to reconstruct three-dimensional biological samples from two-dimensional projections.…

Image and Video Processing · Electrical Eng. & Systems 2023-10-17 Valentin Debarnot , Sidharth Gupta , Konik Kothari , Ivan Dokmanic
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