PickET: An unsupervised method for localizing macromolecules in cryo-electron tomograms Article Swipe

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Shreyas Arvindekar , Omkar Golatkar , Shruthi Viswanath ·

YOU? · · 2025 · Open Access · · DOI: https://doi.org/10.1101/2025.08.20.671250

Cryo-electron tomography (cryo-ET) datasets are rich sources of information capable of describing the localizations, structures, and interactions of macromolecules. However, most current methods for localizing particles in cryo-electron tomograms are limited to macromolecules with known structure, require extensive manual annotations, and/or are computationally expensive. Here, we present PickET, a method for localizing macromolecules in tomograms that does not rely on expert annotations and prior structures. Its performance is demonstrated on a diverse dataset comprising over a hundred tomograms from publicly available datasets, varying in sample types, sample preparation conditions, microscope hardware, and image processing workflows. We demonstrate that PickET can simultaneously localize macromolecules of various shapes, sizes, and abundance. The predicted particle localizations can be used for 3D classification and de novo structural characterization. Our fully unsupervised approach is efficient and scalable, and enables high-throughput analysis of cryo-ET data.

Related Topics

Macromolecule

Cryogenic Electron Microscopy

Computer Science

Tomography

Artificial Intelligence

Transmission Electron Microscopy

Biophysics

Scanning Transmission Electron Microscopy

Concepts

Electron tomography Cryo-electron tomography Macromolecule Cryo-electron microscopy Computer science Sample (material) Workflow Tomography Scalability Single particle analysis Artificial intelligence Biological system Pattern recognition (psychology) Nanotechnology Materials science Chemistry Physics Optics Biology Transmission electron microscopy Biophysics Scanning transmission electron microscopy Chromatography Biochemistry Organic chemistry Aerosol Database

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Type: preprint
Language: en
Landing Page: https://doi.org/10.1101/2025.08.20.671250
PDF: https://www.biorxiv.org/content/biorxiv/early/2025/08/21/2025.08.20.671250.full.pdf
OA Status: green
References: 51
Related Works: 10
OpenAlex ID: https://openalex.org/W4413397577

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DOI: https://doi.org/10.1101/2025.08.20.671250

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Title: PickET: An unsupervised method for localizing macromolecules in cryo-electron tomograms

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Type: preprint

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Language: en

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Publication year: 2025

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Publication date: 2025-08-21

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Authors: Shreyas Arvindekar, Omkar Golatkar, Shruthi Viswanath

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Landing page: https://doi.org/10.1101/2025.08.20.671250

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PDF URL: https://www.biorxiv.org/content/biorxiv/early/2025/08/21/2025.08.20.671250.full.pdf

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Concepts: Electron tomography, Cryo-electron tomography, Macromolecule, Cryo-electron microscopy, Computer science, Sample (material), Workflow, Tomography, Scalability, Single particle analysis, Artificial intelligence, Biological system, Pattern recognition (psychology), Nanotechnology, Materials science, Chemistry, Physics, Optics, Biology, Transmission electron microscopy, Biophysics, Scanning transmission electron microscopy, Chromatography, Biochemistry, Organic chemistry, Aerosol, Database

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