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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

Resolving the structural variability of proteins is often key to understanding the structure-function relationship of those macromolecular machines. Single particle analysis using Cryogenic electron microscopy (CryoEM), combined with…

Quantitative Methods · Quantitative Biology 2022-11-22 Muyuan Chen , Bogdan Toader , Roy Lederman

Transmission electron microscopy (TEM) is a potent technique for the determination of three-dimensional atomic scale structure of samples in structural biology and materials science. In structural biology, three-dimensional structures of…

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

Cryo-electron microscopy (cryo-EM) studies using single particle reconstruction is extensively used to reveal structural information of macromolecular complexes. Aiming at the highest achievable resolution, state of the art electron…

Computer Vision and Pattern Recognition · Computer Science 2020-05-04 Ramin Norousi , Stephan Wickles , Thomas Becker , Roland Beckmann , Volker J. Schmid , Achim Tresch

Single-particle reconstruction in cryo-electron microscopy (cryo-EM) is an increasingly popular technique for determining the 3-D structure of a molecule from several noisy 2-D projections images taken at unknown viewing angles. Most…

Numerical Analysis · Mathematics 2020-04-22 Nir Sharon , Joe Kileel , Yuehaw Khoo , Boris Landa , Amit Singer

Cryo-electron microscopy (cryo-EM) is a widely used technique for recovering the 3-D structure of biological molecules from a large number of experimentally generated noisy 2-D tomographic projection images of the 3-D structure, taken from…

Numerical Analysis · Mathematics 2025-11-17 Jeremy Hoskins , Yuehaw Khoo , Oscar Mickelin , Amit Singer , Yuguan Wang

Electron cryomicroscopy (cryo-EM) is a technique in structural biology used to reconstruct accurate volumetric maps of molecules. One step of the cryo-EM pipeline involves solving an inverse-problem. This inverse-problem, referred to as…

Quantitative Methods · Quantitative Biology 2024-11-26 Aaditya V. Rangan , Wai-Shing Tang , Pilar Cossio , Kexin Zhang , Nikolaus Grigorieff

Phase reconstruction is important in transmission electron microscopy for structural studies. We describe electron Fourier ptychography and its application to phase reconstruction of both radiation-resistant and beam-sensitive materials. We…

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…

We presented a new 3D refinement method for Cryo-EM single particle analysis which can improve the resolution of final electron density map in this paper. We proposed to enforce both sparsity and smoothness to improve the regularity of…

Image and Video Processing · Electrical Eng. & Systems 2020-03-12 Zhenwei Luo

Advances in imagery at atomic and near-atomic resolution, such as cryogenic electron microscopy (cryo-EM), have led to an influx of high resolution images of proteins and other macromolecular structures to data banks worldwide. Producing a…

Quantitative Methods · Quantitative Biology 2021-04-06 Nathan Ranno , Dong Si

Motivation: Structural heterogeneity in single-particle cryo-electron microscopy (cryo-EM) data represents a major challenge for high-resolution structure determination. Unsupervised classification may serve as the first step in the…

Data Analysis, Statistics and Probability · Physics 2017-11-01 Jiayi Wu , Yong-Bei Ma , Charles Congdon , Bevin Brett , Shuobing Chen , Qi Ouyang , Youdong Mao

High-resolution structure determination by cryo-electron microscopy (cryo-EM) requires the accurate fitting of an atomic model into an experimental density map. Traditional refinement pipelines such as Phenix.real_space_refine and Rosetta…

Biomolecules · Quantitative Biology 2026-03-10 Fuyao Huang , Xiaozhu Yu , Kui Xu , Qiangfeng Cliff Zhang

We introduce DiffFit, a differentiable algorithm for fitting protein atomistic structures into an experimental reconstructed Cryo-Electron Microscopy (cryo-EM) volume map. In structural biology, this process is necessary to…

Quantitative Methods · Quantitative Biology 2025-01-09 Deng Luo , Zainab Alsuwaykit , Dawar Khan , Ondřej Strnad , Tobias Isenberg , Ivan Viola

Single-particle cryo-EM has transformed structural biology but still faces challenges in resolving conformational heterogeneity at atomic resolution. Existing cryo-EM heterogeneity analysis methods either lack atomic details or tend to…

Biomolecules · Quantitative Biology 2025-10-21 Chengwei Zhang , Shimian Li , Yihao Niu , Zhen Zhu , Sihao Yuan , Sirui Liu , Yi Qin Gao

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

Cryo-electron microscopy (cryo-EM) enables the atomic-resolution visualization of biomolecules; however, modern direct detectors generate data volumes that far exceed the available storage and transfer bandwidth, thereby constraining…

Image and Video Processing · Electrical Eng. & Systems 2026-03-31 Zain Shabeeb , Daniel Saeedi , Darin Tsui , Vida Jamali , Amirali Aghazadeh

In single particle reconstruction (SPR) from cryo-electron microscopy (cryo-EM), the 3D structure of a molecule needs to be determined from its 2D projection images taken at unknown viewing directions. Zvi Kam showed already in 1980 that…

Computer Vision and Pattern Recognition · Computer Science 2016-02-24 Tejal Bhamre , Teng Zhang , Amit Singer

A central problem in neuroscience is reconstructing neuronal circuits on the synapse level. Due to a wide range of scales in brain architecture such reconstruction requires imaging that is both high-resolution and high-throughput. Existing…

Computer Vision and Pattern Recognition · Computer Science 2012-10-03 Tao Hu , Juan Nunez-Iglesias , Shiv Vitaladevuni , Lou Scheffer , Shan Xu , Mehdi Bolorizadeh , Harald Hess , Richard Fetter , Dmitri Chklovskii
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