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一种基于深度学习的冷冻电子显微镜中粒子修剪方法。

, a deep learning-based approach for particle pruning in cryo-electron microscopy.

作者信息

Sanchez-Garcia Ruben, Segura Joan, Maluenda David, Carazo Jose Maria, Sorzano Carlos Oscar S

机构信息

Biocomputing Unit, Spanish National Center for Biotechnology, Calle Darwin 3, 28049 Madrid, Spain.

出版信息

IUCrJ. 2018 Oct 30;5(Pt 6):854-865. doi: 10.1107/S2052252518014392. eCollection 2018 Nov 1.

DOI:10.1107/S2052252518014392
PMID:30443369
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6211526/
Abstract

Single-particle cryo-electron microscopy (cryo-EM) has recently become a mainstream technique for the structural determination of macromolecules. Typical cryo-EM workflows collect hundreds of thousands of single-particle projections from thousands of micrographs using particle-picking algorithms. However, the number of false positives selected by these algorithms is large, so that a number of different 'cleaning steps' are necessary to decrease the false-positive ratio. Most commonly employed techniques for the pruning of false-positive particles are time-consuming and require user intervention. In order to overcome these limitations, a deep learning-based algorithm named is presented in this work. works by computing a smart consensus over the output of different particle-picking algorithms, resulting in a set of particles with a lower false-positive ratio than the initial set obtained by the pickers. is based on a deep convolutional neural network that is trained on a semi-automatically generated data set. The performance of has been assessed on two well known experimental data sets, virtually eliminating user intervention for pruning, and enhances the reproducibility and objectivity of the whole process while achieving precision and recall figures above 90%.

摘要

单颗粒冷冻电子显微镜技术(cryo-EM)近来已成为用于确定大分子结构的主流技术。典型的cryo-EM工作流程使用颗粒挑选算法从数千张显微照片中收集数十万张单颗粒投影。然而,这些算法挑选出的假阳性数量很多,因此需要一些不同的“清理步骤”来降低假阳性率。最常用的去除假阳性颗粒的技术耗时且需要用户干预。为了克服这些局限性,本文提出了一种基于深度学习的算法名为 。 通过对不同颗粒挑选算法的输出进行智能共识计算来工作,从而得到一组假阳性率低于挑选器获得的初始集合的颗粒。 基于一个在半自动生成的数据集上训练的深度卷积神经网络。 的性能已在两个著名的实验数据集上进行了评估,几乎消除了用户对修剪的干预,并在实现精度和召回率高于90%的同时提高了整个过程的可重复性和客观性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/2c37b36ad5ca/m-05-00854-fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/bfe4ad947e5d/m-05-00854-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/6a2f610f311a/m-05-00854-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/ec1803d9c7cc/m-05-00854-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/c04470edfd9a/m-05-00854-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/7317671610eb/m-05-00854-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/daf39b8de4c0/m-05-00854-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/48937da238f5/m-05-00854-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/29faf74d5cae/m-05-00854-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/02f2d9123046/m-05-00854-fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/2c37b36ad5ca/m-05-00854-fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/bfe4ad947e5d/m-05-00854-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/6a2f610f311a/m-05-00854-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/ec1803d9c7cc/m-05-00854-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/c04470edfd9a/m-05-00854-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/7317671610eb/m-05-00854-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/daf39b8de4c0/m-05-00854-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/48937da238f5/m-05-00854-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/29faf74d5cae/m-05-00854-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/02f2d9123046/m-05-00854-fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4448/6211526/2c37b36ad5ca/m-05-00854-fig10.jpg

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The potential use of single-particle electron microscopy as a tool for structure-based inhibitor design.单颗粒电子显微镜在基于结构的抑制剂设计中的潜在应用。
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