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Motivated by the problem of determining the atomic structure of macromolecules using single-particle cryo-electron microscopy (cryo-EM), we study the sample and computational complexities of the sparse multi-reference alignment (MRA) model:…

Information Theory · Computer Science 2021-09-27 Tamir Bendory , Oscar Mickelin , Amit Singer

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

Single-particle cryo-electron microscopy (cryo-EM) has recently joined X-ray crystallography and NMR spectroscopy as a high-resolution structural method to resolve biological macromolecules. In a cryo-EM experiment, the microscope produces…

Information Theory · Computer Science 2022-10-28 Tamir Bendory , Nicolas Boumal , William Leeb , Eitan Levin , Amit Singer

Single-Particle Reconstruction (SPR) in Cryo-Electron Microscopy (cryo-EM) is the task of estimating the 3D structure of a molecule from a set of noisy 2D projections, taken from unknown viewing directions. Many algorithms for SPR start…

Optimization and Control · Mathematics 2018-01-09 Eitan Levin , Tamir Bendory , Nicolas Boumal , Joe Kileel , Amit Singer

Cryo-electron microscopy (cryo-EM) has recently emerged as a powerful tool for obtaining three-dimensional (3D) structures of biological macromolecules in native states. A minimum cryo-EM image data set for deriving a meaningful…

Applications · Statistics 2014-04-28 Ting-Li Chen , Dai-Ni Hsieh , Hung Hung , I-Ping Tu , Pei-Shien Wu , Yi-Ming Wu , Wei-Hau Chang , Su-Yun Huang

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

Multi-reference alignment (MRA) is the problem of recovering a signal from its multiple noisy copies, each acted upon by a random group element. MRA is mainly motivated by single-particle cryo-electron microscopy (cryo-EM) that has recently…

Information Theory · Computer Science 2023-08-15 Tamir Bendory , Dan Edidin

A single-particle cryo-electron microscopy (cryo-EM) measurement, called a micrograph, consists of multiple two-dimensional tomographic projections of a three-dimensional (3-D) molecular structure at unknown locations, taken under unknown…

Image and Video Processing · Electrical Eng. & Systems 2026-03-10 Shay Kreymer , Amit Singer , Tamir Bendory

We consider the multi-target detection problem of recovering a set of signals that appear multiple times at unknown locations in a noisy measurement. In the low noise regime, one can estimate the signals by first detecting occurrences, then…

Information Theory · Computer Science 2020-01-08 Tamir Bendory , Nicolas Boumal , William Leeb , Eitan Levin , Amit Singer

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

In this report we study the problem of determining three-dimensional orientations for noisy projections of randomly oriented identical particles. The problem is of central importance in the tomographic reconstruction of the density map of…

Data Structures and Algorithms · Computer Science 2007-05-23 Taneli Mielikäinen , Janne Ravantti , Esko Ukkonen

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

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

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

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

We introduce a framework for recovering an image from its rotationally and translationally invariant features based on autocorrelation analysis. This work is an instance of the multi-target detection statistical model, which is mainly used…

Image and Video Processing · Electrical Eng. & Systems 2022-03-03 Nicholas F. Marshall , Ti-Yen Lan , Tamir Bendory , Amit Singer

The computational pipelines of single-particle cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET) include an early particle-picking stage, in which a micrograph or tomogram is scanned to extract candidate particles,…

Signal Processing · Electrical Eng. & Systems 2026-04-14 Amnon Balanov , Alon Zabatani , Tamir Bendory

Cryo-electron microscopy (cryo-EM) enables single-particle analysis of biological macromolecules under strict low-dose imaging conditions, but the resulting micrographs often exhibit extremely low signal-to-noise ratios and weak particle…

Computer Vision and Pattern Recognition · Computer Science 2026-04-21 Xiaoqi Wu , Xueying Zhan , Wen Li , Junhao Wu , Xin Huang , Min Xu

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

Cryo-electron microscopy (cryo-EM) has become a tool of fundamental importance in structural biology, helping us understand the basic building blocks of life. The algorithmic challenge of cryo-EM is to jointly estimate the unknown 3D poses…

Computer Vision and Pattern Recognition · Computer Science 2022-09-01 Axel Levy , Frédéric Poitevin , Julien Martel , Youssef Nashed , Ariana Peck , Nina Miolane , Daniel Ratner , Mike Dunne , Gordon Wetzstein
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