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Motivated by the task of 2-D classification in single particle reconstruction by cryo-electron microscopy (cryo-EM), we consider the problem of heterogeneous multireference alignment of images. In this problem, the goal is to estimate a…

Image and Video Processing · Electrical Eng. & Systems 2019-10-03 Chao Ma , Tamir Bendory , Nicolas Boumal , Fred Sigworth , Amit Singer

Determining the three-dimensional structure of proteins and protein complexes at atomic resolution is a fundamental task in structural biology. Over the last decade, remarkable progress has been made using "single particle" cryo-electron…

Numerical Analysis · Mathematics 2017-06-05 Alex Barnett , Leslie Greengard , Andras Pataki , Marina Spivak

The three-dimensional structure of proteins plays a crucial role in determining their function. Protein structure prediction methods, like AlphaFold, offer rapid access to a protein structure. However, large protein complexes cannot be…

Biomolecules · Quantitative Biology 2025-03-05 Gabriel Ducrocq , Lukas Grunewald , Sebastian Westenhoff , Fredrik Lindsten

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

Estimating the disturbance or clutter covariance is a centrally important problem in radar space time adaptive processing (STAP). The disturbance covariance matrix should be inferred from training sample observations in practice. Large…

Applications · Statistics 2016-02-22 Bosung Kang

Cryo-electron microscopy (cryo-EM) is an experimental technique for protein structure determination that images an ensemble of macromolecules in near-physiological contexts. While recent advances enable the reconstruction of dynamic…

Cryo-electron tomography (cryo-ET) enables in situ visualization of macromolecular structures, where subtomogram analysis tasks such as classification, alignment, and averaging are critical for structural determination. However, effective…

Computer Vision and Pattern Recognition · Computer Science 2025-10-07 Runmin Jiang , Wanyue Feng , Yuntian Yang , Shriya Pingulkar , Hong Wang , Xi Xiao , Xiaoyu Cao , Genpei Zhang , Xiao Wang , Xiaolong Wu , Tianyang Wang , Yang Liu , Xingjian Li , Min Xu

We address the problem of structured covariance matrix estimation for radar space-time adaptive processing (STAP). A priori knowledge of the interference environment has been exploited in many previous works to enable accurate estimators…

Methodology · Statistics 2016-02-18 Bosung Kang , Vishal Monga , Muralidhar Rangaswamy , Yuri I. Abramovich

Cryo-electron microscopy (cryo-EM) emerges as a pivotal technology for determining the architecture of cells, viruses, and protein assemblies at near-atomic resolution. Traditional particle picking, a key step in cryo-EM, struggles with…

Biomolecules · Quantitative Biology 2024-04-17 Chentianye Xu , Xueying Zhan , Min Xu

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…

Background and Objective: The contrast of cryo-EM images varies from one to another, primarily due to the uneven thickness of the ice layer. This contrast variation can affect the quality of 2-D class averaging, 3-D ab-initio modeling, and…

Computer Vision and Pattern Recognition · Computer Science 2022-07-01 Yunpeng Shi , Amit Singer

Understanding protein flexibility and its dynamic interactions with other molecules is essential for studying protein function. Although cryogenic electron microscopy(cryo-EM) provides an opportunity to observe macromolecular dynamics…

Computer Vision and Pattern Recognition · Computer Science 2026-02-03 Bintao He , Yiran Cheng , Hongjia Li , Xiang Gao , Xin Gao , Fa Zhang , Renmin Han

Covariance matrices are important tools for obtaining reliable parameter constraints. Advancements in cosmological surveys lead to larger data vectors and, consequently, increasingly complex covariance matrices, whose number of elements…

Cosmology and Nongalactic Astrophysics · Physics 2022-05-31 Tassia Ferreira , Valerio Marra

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…

Modeling the time-varying covariance structures of high-dimensional variables is critical across diverse scientific and industrial applications; however, existing approaches exhibit notable limitations in either modeling flexibility or…

Methodology · Statistics 2026-01-21 Taehee Lee , Jun S. Liu

The growing role of data-driven approaches to scientific discovery has unveiled a large class of models that involve latent transformations with a rigid algebraic constraint. Three-dimensional molecule reconstruction in Cryo-Electron…

Information Theory · Computer Science 2019-06-04 Amelia Perry , Jonathan Weed , Afonso S. Bandeira , Philippe Rigollet , Amit Singer

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

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

Super-resolution light microscopy overcomes the physical barriers due to light diffraction, allowing for the observation of otherwise indistinguishable subcellular entities. However, the specific acquisition conditions required by…

The application of standard sufficient dimension reduction methods for reducing the dimension space of predictors without losing regression information requires inverting the covariance matrix of the predictors. This has posed a number of…

Methodology · Statistics 2019-10-01 Kabir Opeyemi Olorede , Waheed Babatunde Yahya