CryoHype: Reconstructing a thousand cryo-EM structures with transformer-based hypernetworks

• URL: http://arxiv.org/abs/2512.06332v1
• Date: Sat, 06 Dec 2025 07:39:09 GMT
• Title: CryoHype: Reconstructing a thousand cryo-EM structures with transformer-based hypernetworks
• Authors: Jeffrey Gu, Minkyu Jeon, Ambri Ma, Serena Yeung-Levy, Ellen D. Zhong,
• Abstract summary: Cryo-electron microscopy (cryo-EM) is an indispensable technique for determining the 3D structures of dynamic biomolecular complexes.<n>We propose CryoHype, a transformer-based hypernetwork for cryo-EM reconstruction that dynamically adjusts the weights of an implicit neural representation.<n>We demonstrate that CryoHype scales to the reconstruction of 1,000 distinct structures from unlabeled cryo-EM images in the fixed-pose setting.
• Score: 16.134667337094378
• License: http://arxiv.org/licenses/nonexclusive-distrib/1.0/
• Abstract: 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.

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