- NSF-PAR ID:
- Xu, Jinbo
- Date Published:
- Journal Name:
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Elofsson, Arne (Ed.)Abstract Motivation Cryoelectron tomography (cryo-ET) visualizes structure and spatial organization of macromolecules and their interactions with other subcellular components inside single cells in the close-to-native state at submolecular resolution. Such information is critical for the accurate understanding of cellular processes. However, subtomogram classification remains one of the major challenges for the systematic recognition and recovery of the macromolecule structures in cryo-ET because of imaging limits and data quantity. Recently, deep learning has significantly improved the throughput and accuracy of large-scale subtomogram classification. However, often it is difficult to get enough high-quality annotated subtomogram data for supervised training due to the enormous expense of labeling. To tackle this problem, it is beneficial to utilize another already annotated dataset to assist the training process. However, due to the discrepancy of image intensity distribution between source domain and target domain, the model trained on subtomograms in source domain may perform poorly in predicting subtomogram classes in the target domain. Results In this article, we adapt a few shot domain adaptation method for deep learning-based cross-domain subtomogram classification. The essential idea of our method consists of two parts: (i) take full advantage of the distribution of plentiful unlabeled target domain data, and (ii) exploit the correlation between the whole source domain dataset and few labeled target domain data. Experiments conducted on simulated and real datasets show that our method achieves significant improvement on cross domain subtomogram classification compared with baseline methods. Availability and implementation Software is available online https://github.com/xulabs/aitom. Supplementary information Supplementary data are available at Bioinformatics online.more » « less
Cryo-Electron Tomography (cryo-ET) is a 3D imaging technology that enables the visualization of subcellular structures in situ at near-atomic resolution. Cellular cryo-ET images help in resolving the structures of macromolecules and determining their spatial relationship in a single cell, which has broad significance in cell and structural biology. Subtomogram classification and recognition constitute a primary step in the systematic recovery of these macromolecular structures. Supervised deep learning methods have been proven to be highly accurate and efficient for subtomogram classification, but suffer from limited applicability due to scarcity of annotated data. While generating simulated data for training supervised models is a potential solution, a sizeable difference in the image intensity distribution in generated data as compared with real experimental data will cause the trained models to perform poorly in predicting classes on real subtomograms.
In this work, we present Cryo-Shift, a fully unsupervised domain adaptation and randomization framework for deep learning-based cross-domain subtomogram classification. We use unsupervised multi-adversarial domain adaption to reduce the domain shift between features of simulated and experimental data. We develop a network-driven domain randomization procedure with ‘warp’ modules to alter the simulated data and help the classifier generalize better on experimental data. We do not use any labeled experimental data to train our model, whereas some of the existing alternative approaches require labeled experimental samples for cross-domain classification. Nevertheless, Cryo-Shift outperforms the existing alternative approaches in cross-domain subtomogram classification in extensive evaluation studies demonstrated herein using both simulated and experimental data.
Supplementary data are available at Bioinformatics online.
Haliloglu, Turkan (Ed.)Cryo-electron tomography (cryo-ET) provides 3D visualization of subcellular components in the near-native state and at sub-molecular resolutions in single cells, demonstrating an increasingly important role in structural biology in situ . However, systematic recognition and recovery of macromolecular structures in cryo-ET data remain challenging as a result of low signal-to-noise ratio (SNR), small sizes of macromolecules, and high complexity of the cellular environment. Subtomogram structural classification is an essential step for such task. Although acquisition of large amounts of subtomograms is no longer an obstacle due to advances in automation of data collection, obtaining the same number of structural labels is both computation and labor intensive. On the other hand, existing deep learning based supervised classification approaches are highly demanding on labeled data and have limited ability to learn about new structures rapidly from data containing very few labels of such new structures. In this work, we propose a novel approach for subtomogram classification based on few-shot learning. With our approach, classification of unseen structures in the training data can be conducted given few labeled samples in test data through instance embedding. Experiments were performed on both simulated and real datasets. Our experimental results show that we can make inference on new structures given only five labeled samples for each class with a competitive accuracy (> 0.86 on the simulated dataset with SNR = 0.1), or even one sample with an accuracy of 0.7644. The results on real datasets are also promising with accuracy > 0.9 on both conditions and even up to 1 on one of the real datasets. Our approach achieves significant improvement compared with the baseline method and has strong capabilities of generalizing to other cellular components.more » « less
Cryo-electron tomography (Cryo-ET) has been regarded as a revolution in structural biology and can reveal molecular sociology. Its unprecedented quality enables it to visualize cellular organelles and macromolecular complexes at nanometer resolution with native conformations. Motivated by developments in nanotechnology and machine learning, establishing machine learning approaches such as classification, detection and averaging for Cryo-ET image analysis has inspired broad interest. Yet, deep learning-based methods for biomedical imaging typically require large labeled datasets for good results, which can be a great challenge due to the expense of obtaining and labeling training data. To deal with this problem, we propose a generative model to simulate Cryo-ET images efficiently and reliably: CryoETGAN. This cycle-consistent and Wasserstein generative adversarial network (GAN) is able to generate images with an appearance similar to the original experimental data. Quantitative and visual grading results on generated images are provided to show that the results of our proposed method achieve better performance compared to the previous state-of-the-art simulation methods. Moreover, CryoETGAN is stable to train and capable of generating plausibly diverse image samples.more » « less
In many real-life image analysis applications, particularly in biomedical research domains, the objects of interest undergo multiple transformations that alter their visual properties while keeping the semantic content unchanged. Disentangling images into semantic content factors and transformations can provide significant benefits into many domain-specific image analysis tasks. To this end, we propose a generic unsupervised framework, Harmony, that simultaneously and explicitly disentangles semantic content from multiple parameterized transformations. Harmony leverages a simple cross-contrastive learning framework with multiple explicitly parameterized latent representations to disentangle content from transformations. To demonstrate the efficacy of Harmony, we apply it to disentangle image semantic content from several parameterized transformations (rotation, translation, scaling, and contrast). Harmony achieves significantly improved disentanglement over the baseline models on several image datasets of diverse domains. With such disentanglement, Harmony is demonstrated to incentivize bioimage analysis research by modeling structural heterogeneity of macromolecules from cryo-ET images and learning transformation-invariant representations of protein particles from single-particle cryo-EM images. Harmony also performs very well in disentangling content from 3D transformations and can perform coarse and fast alignment of 3D cryo-ET subtomograms. Therefore, Harmony is generalizable to many other imaging domains and can potentially be extended to domains beyond imaging as well.more » « less