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Main Authors: Gu, Jeffrey, Jeon, Minkyu, Ma, Ambri, Yeung-Levy, Serena, Zhong, Ellen D.
Format: Preprint
Published: 2025
Subjects:
Online Access:https://arxiv.org/abs/2512.06332
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author Gu, Jeffrey
Jeon, Minkyu
Ma, Ambri
Yeung-Levy, Serena
Zhong, Ellen D.
author_facet Gu, Jeffrey
Jeon, Minkyu
Ma, Ambri
Yeung-Levy, Serena
Zhong, Ellen D.
contents Cryo-electron microscopy (cryo-EM) is an indispensable technique for determining the 3D structures of dynamic biomolecular complexes. While typically applied to image a single molecular species, cryo-EM has the potential for structure determination of many targets simultaneously in a high-throughput fashion. However, existing methods typically focus on modeling conformational heterogeneity within a single or a few structures and are not designed to resolve compositional heterogeneity arising from mixtures of many distinct molecular species. To address this challenge, we propose CryoHype, a transformer-based hypernetwork for cryo-EM reconstruction that dynamically adjusts the weights of an implicit neural representation. Using CryoHype, we achieve state-of-the-art results on a challenging benchmark dataset containing 100 structures. We further demonstrate that CryoHype scales to the reconstruction of 1,000 distinct structures from unlabeled cryo-EM images in the fixed-pose setting.
format Preprint
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institution arXiv
publishDate 2025
record_format arxiv
spellingShingle CryoHype: Reconstructing a thousand cryo-EM structures with transformer-based hypernetworks
Gu, Jeffrey
Jeon, Minkyu
Ma, Ambri
Yeung-Levy, Serena
Zhong, Ellen D.
Computer Vision and Pattern Recognition
Cryo-electron microscopy (cryo-EM) is an indispensable technique for determining the 3D structures of dynamic biomolecular complexes. While typically applied to image a single molecular species, cryo-EM has the potential for structure determination of many targets simultaneously in a high-throughput fashion. However, existing methods typically focus on modeling conformational heterogeneity within a single or a few structures and are not designed to resolve compositional heterogeneity arising from mixtures of many distinct molecular species. To address this challenge, we propose CryoHype, a transformer-based hypernetwork for cryo-EM reconstruction that dynamically adjusts the weights of an implicit neural representation. Using CryoHype, we achieve state-of-the-art results on a challenging benchmark dataset containing 100 structures. We further demonstrate that CryoHype scales to the reconstruction of 1,000 distinct structures from unlabeled cryo-EM images in the fixed-pose setting.
title CryoHype: Reconstructing a thousand cryo-EM structures with transformer-based hypernetworks
topic Computer Vision and Pattern Recognition
url https://arxiv.org/abs/2512.06332