Novel machine learning approaches for improving structural discrimination in cryo-electron tomography

用于改善冷冻电子断层扫描结构辨别的新型机器学习方法

• 批准号: 10620355
• 负责人: Min Xu
• 金额: $ 32.67万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-10 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10620355
• 关键词: 3-Dimensional; Acceleration; Address; Algorithms; Back; Benchmarking; Biological Process; Cells; Communities; Computer Analysis; Computer software; Cryo-electron tomography; Data; Data Analyses; Data Set; Detection; Discrimination; Evaluation; Future; Hour; Image; In Situ; Knowledge; Laplacian; Literature; Machine Learning; Macromolecular Complexes; Manuals; Methods; Mitochondria; Modeling; Molecular Conformation; Monitor; Neurophysiology - biologic function; Noise; Organelles; Performance; Process; Publishing; Reporting; Resolution; Series; Signal Transduction; Structure; System; Techniques; Testing; Tomogram; Visualization; Weight; Work; autoencoder; automated algorithm; deep learning; design; falls; feature detection; graphical user interface; improved; innovation; insight; machine learning algorithm; nano; nanometer resolution; novel; novel strategies; open source; particle; pi-Mesons; programs; reconstruction; success; user-friendly

Project Summary Cellular cryo-electron tomography (Cryo-ET) has made possible the observation of cellular organelles and macromolecular complexes at nanometer resolution with native conformations. The rapid increasing amount of Cryo-ET data available however brings along some major challenges for analysis which we will timely ad- dress in this proposal. We will design novel data-driven machine learning algorithms for improving structural discrimination and resolution. In particular, we have the following specific aims: (1) We will develop a novel Autoencoder and Iterative region Matching (AIM) algorithm for marker-free alignment of image tilt-series to re- construct tomograms with improved resolution; (2) We will develop a saliency-based auto-picking algorithm for better detecting macromolecular complexes, and combine it with an innovative 2D-to-3D framework to further improve structure detection accuracy; (3) We will design an end-to-end convolutional model for pose-invariant clustering of subtomograms. This model will produce an initial clustering which will be refined by a new subto- mogram averaging algorithm that automatically down-weights subtomograms of noise and little contribution; (4) We will perform experimental evaluations by using previously reported bacterial secretion systems and mito- chondrial ultrastructures datasets to improve the final resolution. Implementing algorithms in Aims 1-3, we will develop a user-friendly open-source graphical user interface -tom to directly benefit the scientific community. -tom will be systematically compared with existing software including IMOD, EMAN2, and Relion on simulated and benchmark datasets. To facilitate distribution, -tom will be integrated into existing software platforms Sci- pion and TomoMiner. Our data-driven algorithms and software not only will facilitate and accelerate the future use of Cryo-ET, but also can be readily used on analyzing the existing large amounts of Cryo-ET data to im- prove our understanding of the structure, function, and spatial organization of macromolecular complexes in situ.

项目摘要 细胞冷冻电子断层扫描（Cryo-ET）使观察细胞器和 带有天然构象的纳米分辨率下的大分子复合物。迅速增加的数量 但是，可用的Cryo-ET数据带来了一些主要的分析挑战 穿上这个建议。我们将设计新颖的数据驱动机器学习算法，以改善结构 歧视和解决方案。特别是，我们具有以下特定目的：（1）我们将开发出小说 自动编码器和迭代区域匹配（AIM）算法，用于图像倾斜系列的无标记对齐 构建具有改进分辨率的断层图； （2）我们将开发一种基于显着的自动选择算法 更好地检测大分子复合物，并将其与创新的2d-3d框架结合起来 提高结构检测准确性； （3）我们将设计姿势不变的端到端卷积模型 亚图表的聚类。该模型将产生初始聚类，该聚类将由新的Subto-to-将 mography平均算法自动减轻噪声的亚图和贡献很少的算法； （4） 我们将通过使用先前报道的细菌分泌系统和Mi​​to-进行实验评估 软骨超结构数据集以改善最终分辨率。在AIMS 1-3中实施算法，我们将 开发一个用户友好的开源图形用户界面-TOM，以直接受益于科学界。 -TOM将与现有软件（包括IMOD，EMAN2和RISION）的现有软件进行系统的比较。 和基准数据集。为了促进分销，-TOM将集成到现有的软件平台中 派和Tomominer。我们的数据驱动算法和软件不仅会促进和加速未来 使用冷冻-ET，但也可以很容易地用于分析现有的大量冷冻数据以进行 证明我们对大分子复合物的结构，功能和空间组织的理解 原位。

项目成果

Deep Active Learning for Cryo-Electron Tomography Classification

• DOI: 10.1109/icip46576.2022.9898002
• 发表时间: 2022-10
• 期刊: 2022 IEEE International Conference on Image Processing (ICIP)
• 作者: Tianyang Wang;Bo Li;Jing Zhang;Xiangrui Zeng;Mostofa Rafid Uddin;Wei Wu;Min Xu

End-to-end robust joint unsupervised image alignment and clustering.

• DOI: 10.1109/iccv48922.2021.00383
• 发表时间: 2021-10
• 期刊: Proceedings. IEEE International Conference on Computer Vision
• 作者: Zeng X;Howe G;Xu M
• 通讯作者: Xu M

Poly(A)-DG: A deep-learning-based domain generalization method to identify cross-species Poly(A) signal without prior knowledge from target species.

• DOI: 10.1371/journal.pcbi.1008297
• 发表时间: 2020-11
• 期刊: PLoS computational biology
• 影响因子: 4.3
• 作者: Zheng Y;Wang H;Zhang Y;Gao X;Xing EP;Xu M
• 通讯作者: Xu M

Harmony: A Generic Unsupervised Approach for Disentangling Semantic Content from Parameterized Transformations.

• DOI: 10.1109/cvpr52688.2022.01999
• 发表时间: 2022-06
• 期刊: Proceedings. IEEE Computer Society Conference on Computer Vision and Pattern Recognition
• 作者: Uddin, Mostofa Rafid;Howe, Gregory;Zeng, Xiangrui;Xu, Min
• 通讯作者: Xu, Min

Few-shot learning for classification of novel macromolecular structures in cryo-electron tomograms.

• DOI: 10.1371/journal.pcbi.1008227
• 发表时间: 2020-11
• 期刊: PLoS computational biology
• 影响因子: 4.3
• 作者: Li R;Yu L;Zhou B;Zeng X;Wang Z;Yang X;Zhang J;Gao X;Jiang R;Xu M
• 通讯作者: Xu M