北京大学学报(医学版) ›› 2021, Vol. 53 ›› Issue (2): 425-433. doi: 10.19723/j.issn.1671-167X.2021.02.033

• 综述 • 上一篇    下一篇

冷冻电镜成像中噪声的滤波方法进展

黄新瑞1,李莎2,高嵩2,Δ()   

  1. 1.北京大学基础医学院生物化学与生物物理学系,北京 100191
    2.北京大学医学部医学技术研究院,北京 100191
  • 收稿日期:2019-03-12 出版日期:2021-04-18 发布日期:2021-04-21
  • 通讯作者: 高嵩 E-mail:gaoss@hsc.pku.edu.cn
  • 基金资助:
    国家自然科学基金(12075011);国家自然科学基金(61901008);北京市自然科学基金(7202093);北京大学临床医学+X青年专项-中央高校基本科研业务费(PKU2020LCXQ004);北大医学青年科技创新培育基金-中央高校基本科研业务费(BMU2018PY003)

Progress in filters for denoising cryo-electron microscopy images

HUANG Xin-rui1,LI Sha2,GAO Song2,Δ()   

  1. 1. Department of Biochemistry and Biophysics, Peking University School of Basic Medical Sciences, Beijing 100191, China
    2. Institute of Medical Technology, Peking University Health Science Center, Beijing 100191, China
  • Received:2019-03-12 Online:2021-04-18 Published:2021-04-21
  • Contact: Song GAO E-mail:gaoss@hsc.pku.edu.cn
  • Supported by:
    National Natural Science Foundation of China(12075011);National Natural Science Foundation of China(61901008);Beijing Natural Science Foundation(7202093);Fundamental Research Funds for the Central Universities: Peking University Clinical Medicine Plus X-Young Scholars Project(PKU2020LCXQ004);Fundamental Research Funds for the Central Universities: Peking University Medicine Fund of Fostering Young Scholars’ Scientific & Technological Innovation(BMU2018PY003)

关键词: 冷冻电子显微镜, 图像处理, 计算机辅助, 成像, 三维, 信噪比

Abstract:

Cryo-electron microscopy (cryo-EM) imaging has the unique potential to bridge the gap between cellular and molecular biology. Therefore, cryo-EM three-dimensional (3D) reconstruction has been rapidly developed in recent several years and applied widely in life science research to reveal the structures of large macromolecular assemblies and cellular complexes, which is critical to understanding their functions at all scales. Although the technical breakthrough in recent years, for example, the introduction of the direct detection device (DDD) camera and the development of cryo-EM software tools, made the three cryo-EM pioneers share the 2017 Nobel Prize, several bottleneck problems still exist that hamper the further increase of the resolution of single-particle reconstruction and hold back the application of in situ subnanometer structure determination by cryo-tomography. Radiation damage is still the key limiting factor in cryo-EM. In order to minimize the radiation damage and preserve as much resolution as possible, the imaging conditions of a low dose and weak contrast make cryo-EM images extremely noisy with very low signal-to-noise ratios (SNR), generally about 0.1. The high noise will obscure the fine details in cryo-EM images or reconstructed maps. Thus, a method to reduce the level of noise and improve the resolution has become an important issue. In this paper, we systematically reviewed and compared some robust filters in the cryo-EM field of two aspects, single-particle analysis (SPA) and cryo-electron tomography (cryo-ET), and especially studied their applications, such as, 3D reconstruction, visualization, structural analysis, and interpretation. Conventional approaches to noise reduction in cryo-EM imaging include the use of Gaussian, median, and bilateral filters, among other means. A Gaussian filter selects an appropriate filter kernel to conduct spatial convolution with a noisy image. Although noise with larger standard deviations in cryo-EM images can be suppressed and satisfactory performance is achieved in certain cases, this filter also blurs the images and over-smooths small-scale image features. This is especially detrimental when precise quantitative information needs to be extracted. Unlike a Gaussian filter, a median filter is based on the order statistics of the image and selects the median intensity in a window of the adjacent pixels to denoise the image. Although this filter is robust to outliers, it suffers from aliasing problems that possibly result in incorrect information for cryo-EM structure interpretation. A bilateral filter is a nonlinear filter that performs spatial weighted averaging and is more selective in the pixels allowing to contribute to the weighted sum, excluding the high frequency noise from the smoothing process. Thus, this filter can be used to smooth out noise while maintaining the edge details, which is similar to an anisotropic diffusion filter, and distinct from a Gaussian filter but its utility will be limited when the SNR of a cryo-EM image is very low. Generally, spatial filtering methods have the disadvantage of losing image resolution when reducing noise. A wavelet transform can exploit the wavelet’s natural ability to separate a signal from noise at multiple image scales to allow for joint resolution in both the spatial and frequency domains, and thus has the potential to outperform existing methods. The modified wavelet shrinkage filter we developed can offer a remarkable improvement in image quality with a good compromise between detail preservation and noise smoothing. We expect that our review study on different filters can provide benefits to cryo-EM applications and the interpretation of biological structures.

Key words: Cryoelectron microscopy, Image processing, computer-assisted, Imaging, three-dimensional, Signal-to-noise ratio

中图分类号: 

  • R312

图1

冷冻电镜图像滤波方法"

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