- PAR ID:
- 10230120
- Editor(s):
- Haliloglu, Turkan
- Date Published:
- Journal Name:
- PLOS Computational Biology
- Volume:
- 16
- Issue:
- 11
- ISSN:
- 1553-7358
- Page Range / eLocation ID:
- e1008227
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Abstract Motivation 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.
Results 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.
Availabilityand implementation https://github.com/xulabs/aitom.
Supplementary information Supplementary data are available at Bioinformatics online.
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Xu, Jinbo (Ed.)Abstract Motivation Cryo-Electron Tomography (cryo-ET) is a 3D bioimaging tool that visualizes the structural and spatial organization of macromolecules at a near-native state in single cells, which has broad applications in life science. However, the systematic structural recognition and recovery of macromolecules captured by cryo-ET are difficult due to high structural complexity and imaging limits. Deep learning-based subtomogram classification has played critical roles for such tasks. As supervised approaches, however, their performance relies on sufficient and laborious annotation on a large training dataset. Results To alleviate this major labeling burden, we proposed a Hybrid Active Learning (HAL) framework for querying subtomograms for labeling from a large unlabeled subtomogram pool. Firstly, HAL adopts uncertainty sampling to select the subtomograms that have the most uncertain predictions. This strategy enforces the model to be aware of the inductive bias during classification and subtomogram selection, which satisfies the discriminativeness principle in AL literature. Moreover, to mitigate the sampling bias caused by such strategy, a discriminator is introduced to judge if a certain subtomogram is labeled or unlabeled and subsequently the model queries the subtomogram that have higher probabilities to be unlabeled. Such query strategy encourages to match the data distribution between the labeled and unlabeled subtomogram samples, which essentially encodes the representativeness criterion into the subtomogram selection process. Additionally, HAL introduces a subset sampling strategy to improve the diversity of the query set, so that the information overlap is decreased between the queried batches and the algorithmic efficiency is improved. Our experiments on subtomogram classification tasks using both simulated and real data demonstrate that we can achieve comparable testing performance (on average only 3% accuracy drop) by using less than 30% of the labeled subtomograms, which shows a very promising result for subtomogram classification task with limited labeling resources. Availability and implementation https://github.com/xulabs/aitom. Supplementary information Supplementary data are available at Bioinformatics online.more » « less
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