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Proteins are dynamic, adopting ensembles of conformations. The nature of this conformational heterogenity is imprinted in the raw electron density measurements obtained from X-ray crystallography experiments. Fitting an ensemble of protein…

Quantitative Methods · Quantitative Biology 2024-12-19 Sai Advaith Maddipatla , Nadav Bojan Sellam , Sanketh Vedula , Ailie Marx , Alex Bronstein

Cryo-ET allows to generate tomograms of biological samples in situ, capturing complex structures in their native context. Despite low signal-to-noise ratio in reconstructed volumes, the large number of copies of the same macromolecules…

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

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

There is a clear need for developments in characterisation techniques that provide detailed information about structure-function relationships in biology. Using electron microscopy to achieve high resolution while maintaining a broad field…

Quantitative Methods · Quantitative Biology 2023-09-12 Chen Huang , Judy S. Kim , Angus I. Kirkland

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

Cryogenic electron microscopy (Cryo-EM) has become an essential tool for capturing high-resolution biological structures. Despite its advantage in visualizations, the large storage size of Cryo-EM data file poses significant challenges for…

Machine Learning · Computer Science 2025-12-16 Chunyu Zou

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

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

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

The CryoEM single particle imaging method has recently received broad attention in the field of structural biology for determining the structures of biological molecules. The structures can be resolved to near-atomic resolutions after…

Biomolecules · Quantitative Biology 2017-12-27 Yihua Wang , Daqi Yu , Qi Ouyang , Haiguang Liu

In biomolecular systems (especially all-atom models) with many degrees of freedom such as proteins and nucleic acids, there exist an astronomically large number of local-minimum-energy states. Conventional simulations in the canonical…

Statistical Mechanics · Physics 2010-12-30 Ayori Mitsutake , Yoshiharu Mori , Yuko Okamoto

Cryo-electron tomography (cryoET) is a technique that captures images of biological samples at different tilts, preserving their native state as much as possible. Along with the partial tilt series and noise, one of the major challenges in…

Signal Processing · Electrical Eng. & Systems 2023-07-26 Vinith Kishore , Valentin Debarnot , Ivan Dokmanić

Cellular Electron Cryotomography (CryoET) offers the ability to look inside cells and observe macromolecules frozen in action. A primary challenge for this technique is identifying and extracting the molecular components within the crowded…

Quantitative Methods · Quantitative Biology 2021-08-04 Muyuan Chen , Wei Dai , Ying Sun , Darius Jonasch , Cynthia Y He , Michael F. Schmid , Wah Chiu , Steven J Ludtke

Particle picking is a time-consuming step in single-particle analysis and often requires significant interventions from users, which has become a bottleneck for future automated electron cryo-microscopy (cryo-EM). Here we report a deep…

Quantitative Methods · Quantitative Biology 2016-05-09 Feng Wang , Huichao Gong , Gaochao liu , Meijing Li , Chuangye Yan , Tian Xia , Xueming Li , Jianyang Zeng

Accurate orientation estimation is a crucial component of 3D molecular structure reconstruction, both in single-particle cryo-electron microscopy (cryo-EM) and in the increasingly popular field of cryo-electron tomography (cryo-ET). The…

Applications · Statistics 2026-02-25 Sheng Xu , Amnon Balanov , Amit Singer , Tamir Bendory

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

We propose a method to reconstruct the 3-D molecular structure from micrographs collected at just one sample tilt angle in the random conical tilt scheme in cryo-electron microscopy. Our method uses autocorrelation analysis on the…

Data Analysis, Statistics and Probability · Physics 2021-01-12 Ti-Yen Lan , Nicolas Boumal , Amit Singer

The central problem in cryo-electron microscopy (cryo-EM) is to recover the 3D structure from noisy 2D projection images which requires estimating the missing projection angles (poses). Recent methods attempted to solve the 3D…

Computer Vision and Pattern Recognition · Computer Science 2023-02-15 Lin Yao , Ruihan Xu , Zhifeng Gao , Guolin Ke , Yuhang Wang

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

The cryo-electron microscope (cryo-EM) is increasingly popular these years. It helps to uncover the biological structures and functions of macromolecules. In this paper, we address image denoising problem in cryo-EM. Denoising the cryo-EM…

Computation · Statistics 2018-10-26 Yin Xian , Hanlin Gu , Wei Wang , Xuhui Huang , Yuan Yao , Yang Wang , Jian-Feng Cai
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