CryoCCD: Conditional Cycle-consistent Diffusion with Biophysical Modeling for Cryo-EM Synthesis

• URL: http://arxiv.org/abs/2505.23444v2
• Date: Fri, 20 Jun 2025 01:15:53 GMT
• Title: CryoCCD: Conditional Cycle-consistent Diffusion with Biophysical Modeling for Cryo-EM Synthesis
• Authors: Runmin Jiang, Genpei Zhang, Yuntian Yang, Siqi Wu, Yuheng Zhang, Wanyue Feng, Yizhou Zhao, Xi Xiao, Xiao Wang, Tianyang Wang, Xingjian Li, Min Xu,
• Abstract summary: We propose CryoCCD, a synthesis framework that integrates biophysical modeling with generative techniques.<n>CryoCCD produces multi-scale cryo-EM micrographs that reflect realistic biophysical variability.<n>Experiments show that CryoCCD generates structurally accurate micrographs and enhances performance in downstream tasks.
• Score: 24.767861540998478
• License: http://arxiv.org/licenses/nonexclusive-distrib/1.0/
• Abstract: Cryo-electron microscopy (cryo-EM) offers near-atomic resolution imaging of macromolecules, but developing robust models for downstream analysis is hindered by the scarcity of high-quality annotated data. While synthetic data generation has emerged as a potential solution, existing methods often fail to capture both the structural diversity of biological specimens and the complex, spatially varying noise inherent in cryo-EM imaging. To overcome these limitations, we propose CryoCCD, a synthesis framework that integrates biophysical modeling with generative techniques. Specifically, CryoCCD produces multi-scale cryo-EM micrographs that reflect realistic biophysical variability through compositional heterogeneity, cellular context, and physics-informed imaging. To generate realistic noise, we employ a conditional diffusion model, enhanced by cycle consistency to preserve structural fidelity and mask-aware contrastive learning to capture spatially adaptive noise patterns. Extensive experiments show that CryoCCD generates structurally accurate micrographs and enhances performance in downstream tasks, outperforming state-of-the-art baselines in both particle picking and reconstruction.

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