DUAL:用于冷冻电子断层扫描的深度无监督同步模拟与去噪
DUAL: deep unsupervised simultaneous simulation and denoising for cryo-electron tomography.
作者信息
Zeng Xiangrui, Ding Yizhe, Zhang Yueqian, Uddin Mostofa Rafid, Dabouei Ali, Xu Min
机构信息
Ray and Stephanie Lane Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, 15213, USA.
Department of Statistics, The Pennsylvania State University, University Park, PA, 16802, USA.
出版信息
bioRxiv. 2024 Mar 6:2024.03.02.583135. doi: 10.1101/2024.03.02.583135.
Recent biotechnological developments in cryo-electron tomography allow direct visualization of native sub-cellular structures with unprecedented details and provide essential information on protein functions/dysfunctions. Denoising can enhance the visualization of protein structures and distributions. Automatic annotation via data simulation can ameliorate the time-consuming manual labeling of large-scale datasets. Here, we combine the two major cryo-ET tasks together in DUAL, by a specific cyclic generative adversarial network with novel noise disentanglement. This enables end-to-end unsupervised learning that requires no labeled data for training. The denoising branch outperforms existing works and substantially improves downstream particle picking accuracy on benchmark datasets. The simulation branch provides learning-based cryo-ET simulation for the first time and generates synthetic tomograms indistinguishable from experimental ones. Through comprehensive evaluations, we showcase the effectiveness of DUAL in detecting macromolecular complexes across a wide range of molecular weights in experimental datasets. The versatility of DUAL is expected to empower cryo-ET researchers by improving visual interpretability, enhancing structural detection accuracy, expediting annotation processes, facilitating cross-domain model adaptability, and compensating for missing wedge artifacts. Our work represents a significant advancement in the unsupervised mining of protein structures in cryo-ET, offering a multifaceted tool that facilitates cryo-ET research.
冷冻电子断层扫描技术最近的生物技术发展使得能够以前所未有的细节直接观察天然亚细胞结构,并提供有关蛋白质功能/功能障碍的重要信息。去噪可以增强蛋白质结构和分布的可视化效果。通过数据模拟进行自动注释可以改善大规模数据集耗时的手动标记。在这里,我们通过具有新颖噪声解缠的特定循环生成对抗网络,将冷冻电子断层扫描的两项主要任务结合在DUAL中。这实现了端到端的无监督学习,无需标记数据进行训练。去噪分支优于现有工作,并在基准数据集上显著提高了下游粒子挑选的准确性。模拟分支首次提供基于学习的冷冻电子断层扫描模拟,并生成与实验图像难以区分的合成断层图像。通过全面评估,我们展示了DUAL在检测实验数据集中广泛分子量范围内的大分子复合物方面的有效性。DUAL的多功能性有望通过提高视觉可解释性、增强结构检测准确性、加快注释过程、促进跨域模型适应性以及补偿缺失楔形伪影来增强冷冻电子断层扫描研究人员的能力。我们的工作代表了冷冻电子断层扫描中蛋白质结构无监督挖掘的重大进展,提供了一个促进冷冻电子断层扫描研究的多方面工具。