A convolutional autoencoder approach for mining features in cellular electron cryo-tomograms and weakly supervised coarse segmentation

Cellular electron cryo-tomography enables the 3D visualization of cellular organization in the near-native state and at submolecular resolution. However, the contents of cellular tomograms are often complex, making it difficult to automatically isolate different in situ cellular components. In this paper, we propose a convolutional autoencoder-based unsupervised approach to provide a coarse grouping of 3D small subvolumes extracted from tomograms. We demonstrate that the autoencoder can be used for efficient and coarse characterization of features of macromolecular complexes and surfaces, such as membranes. In addition, the autoencoder can be used to detect non-cellular features related to sample preparation and data collection, such as carbon edges from the grid and tomogram boundaries. The autoencoder is also able to detect patterns that may indicate spatial interactions between cellular components. Furthermore, we demonstrate that our autoencoder can be used for weakly supervised semantic segmentation of cellular components, requiring a very small amount of manual annotation.Comment: Accepted by Journal of Structural Biolog

Active Learning to Classify Macromolecular Structures in situ for Less Supervision in Cryo-Electron Tomography

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 have 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 labelling from a large unlabeled subtomogram pool. Firstly, HAL adopts uncertainty sampling to select the subtomograms that have the most uncertain predictions. 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. 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.Comment: Statement on authorship changes: Dr. Eric Xing was an academic advisor of Mr. Haohan Wang. Dr. Xing was not directly involved in this work and has no direct interaction or collaboration with any other authors on this work. Therefore, Dr. Xing is removed from the author list according to his request. Mr. Zhenxi Zhu's affiliation is updated to his current affiliatio

3D ConvNet improves macromolecule localization in 3D cellular cryo-electron tomograms

Cryo-electron tomography (cryo-ET) allows one to capture 3D images of cells in a close to native state, at sub-nanometer resolution. However, noise and artifact levels are such that heavy computational processing is needed to access the image content. In this paper, we propose a deep learning framework to accurately and jointly localize multiple types and states of macromolecules in cellular cryo-electron tomograms. We compare this framework to the commonly-used template matching method on both synthetic and experimental data. On synthetic image data, we show that our framework is very fast and produces superior detection results. On experimental data, the detection results obtained by our method correspond to an overlap rate of 86% with the expert annotations, and comparable resolution is achieved when applying subtomogram averaging. In addition, we show that our method can be combined to template matching procedures to reliably increase the number of expected detections. In our experiments, this strategy was able to find additional 20.5% membrane-bound ribosomes that were missed or discarded during manual annotation