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面向冷冻电子断层扫描数据中无偏模式挖掘和结构确定的计算方法。

Computational Methods Toward Unbiased Pattern Mining and Structure Determination in Cryo-Electron Tomography Data.

机构信息

Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: https://twitter.com/hannahinthelab.

Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, USA. Electronic address: https://twitter.com/duran_rafid.

出版信息

J Mol Biol. 2023 May 1;435(9):168068. doi: 10.1016/j.jmb.2023.168068. Epub 2023 Mar 31.

Abstract

Cryo-electron tomography can uniquely probe the native cellular environment for macromolecular structures. Tomograms feature complex data with densities of diverse, densely crowded macromolecular complexes, low signal-to-noise, and artifacts such as the missing wedge effect. Post-processing of this data generally involves isolating regions or particles of interest from tomograms, organizing them into related groups, and rendering final structures through subtomogram averaging. Template-matching and reference-based structure determination are popular analysis methods but are vulnerable to biases and can often require significant user input. Most importantly, these approaches cannot identify novel complexes that reside within the imaged cellular environment. To reliably extract and resolve structures of interest, efficient and unbiased approaches are therefore of great value. This review highlights notable computational software and discusses how they contribute to making automated structural pattern discovery a possibility. Perspectives emphasizing the importance of features for user-friendliness and accessibility are also presented.

摘要

冷冻电子断层扫描技术可以独特地探测到大分子结构的天然细胞环境。断层扫描图像具有复杂的数据特征,包括密度不同、高度拥挤的大分子复合物、低信噪比以及缺失楔形效应等伪影。对这些数据的后处理通常涉及从断层扫描图像中分离感兴趣的区域或颗粒,将它们组织成相关的组,并通过子断层平均化来呈现最终的结构。模板匹配和基于参考的结构确定是流行的分析方法,但容易受到偏差的影响,并且通常需要大量的用户输入。最重要的是,这些方法无法识别存在于成像细胞环境中的新型复合物。因此,为了可靠地提取和解析感兴趣的结构,高效且无偏的方法具有重要价值。本文综述了显著的计算软件,并讨论了它们如何有助于实现自动化结构模式发现的可能性。本文还强调了用户友好性和可访问性的重要性。

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