A unified framework for packing deformable and non-deformable subcellular structures in crowded cryo-electron tomogram s
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METHODOLOGY ARTICLE
Open Access
A unified framework for packing deformable and non-deformable subcellular structures in crowded cryo-electron tomogram simulation Sinuo Liu1,2 , Xiaojuan Ban1*† , Xiangrui Zeng2 , Fengnian Zhao3 , Yuan Gao2 , Wenjie Wu4 , Hongpan Zhang5,6 , Feiyang Chen7 , Thomas Hall2 , Xin Gao8 and Min Xu2* † *Correspondence: [email protected]; [email protected] † Xiaojuan Ban and Min Xu contributed equally to this work. 1 Beijing Advanced Innovation Center for Materials Genome Engineering, School of Computer and Communication Engineering, University of Science and Technology Beijing, Beijing, China 2 Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, United States Full list of author information is available at the end of the article
Abstract Background: Cryo-electron tomography is an important and powerful technique to explore the structure, abundance, and location of ultrastructure in a near-native state. It contains detailed information of all macromolecular complexes in a sample cell. However, due to the compact and crowded status, the missing edge effect, and low signal to noise ratio (SNR), it is extremely challenging to recover such information with existing image processing methods. Cryo-electron tomogram simulation is an effective solution to test and optimize the performance of the above image processing methods. The simulated images could be regarded as the labeled data which covers a wide range of macromolecular complexes and ultrastructure. To approximate the crowded cellular environment, it is very important to pack these heterogeneous structures as tightly as possible. Besides, simulating non-deformable and deformable components under a unified framework also need to be achieved. Result: In this paper, we proposed a unified framework for simulating crowded cryo-electron tomogram images including non-deformable macromolecular complexes and deformable ultrastructures. A macromolecule was approximated using multiple balls with fixed relative positions to reduce the vacuum volume. A ultrastructure, such as membrane and filament, was approximated using multiple balls with flexible relative positions so that this structure could deform under force field. In the experiment, 400 macromolecules of 20 representative types were packed into simulated cytoplasm by our framework, and numerical verification proved (Continued on next page)
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