Qiang Guo

Chang Liu, Xiangrui Zeng, Kaiwen Wang et al.

Cellular Electron Cryo-Tomography (CECT) is a powerful 3D imaging tool for studying the native structure and organization of macromolecules inside single cells. For systematic recognition and recovery of macromolecular structures captured by CECT, methods for several important tasks such as subtomogram classification and semantic segmentation have been developed. However, the recognition and recovery of macromolecular structures are still very difficult due to high molecular structural diversity, crowding molecular environment, and the imaging limitations of CECT. In this paper, we propose a novel multi-task 3D convolutional neural network model for simultaneous classification, segmentation, and coarse structural recovery of macromolecules of interest in subtomograms. In our model, the learned image features of one task are shared and thereby mutually reinforce the learning of other tasks. Evaluated on realistically simulated and experimental CECT data, our multi-task learning model outperformed all single-task learning methods for classification and segmentation. In addition, we demonstrate that our model can generalize to discover, segment and recover novel structures that do not exist in the training data.

Yixiu Zhao, Xiangrui Zeng, Qiang Guo et al.

Motivation: Cellular Electron CryoTomography (CECT) is an emerging 3D imaging technique that visualizes subcellular organization of single cells at submolecular resolution and in near-native state. CECT captures large numbers of macromolecular complexes of highly diverse structures and abundances. However, the structural complexity and imaging limits complicate the systematic de novo structural recovery and recognition of these macromolecular complexes. Efficient and accurate reference-free subtomogram averaging and classification represent the most critical tasks for such analysis. Existing subtomogram alignment based methods are prone to the missing wedge effects and low signal-to-noise ratio (SNR). Moreover, existing maximum-likelihood based methods rely on integration operations, which are in principle computationally infeasible for accurate calculation. Results: Built on existing works, we propose an integrated method, Fast Alignment Maximum Likelihood method (FAML), which uses fast subtomogram alignment to sample sub-optimal rigid transformations. The transformations are then used to approximate integrals for maximum-likelihood update of subtomogram averages through expectation-maximization algorithm. Our tests on simulated and experimental subtomograms showed that, compared to our previously developed fast alignment method (FA), FAML is significantly more robust to noise and missing wedge effects with moderate increases of computation cost.Besides, FAML performs well with significantly fewer input subtomograms when the FA method fails. Therefore, FAML can serve as a key component for improved construction of initial structural models from macromolecules captured by CECT.

Bo Zhou, Qiang Guo, Xiangrui Zeng et al.

Electron Cryo-Tomography (ECT) allows 3D visualization of subcellular structures at the submolecular resolution in close to the native state. However, due to the high degree of structural complexity and imaging limits, the automatic segmentation of cellular components from ECT images is very difficult. To complement and speed up existing segmentation methods, it is desirable to develop a generic cell component segmentation method that is 1) not specific to particular types of cellular components, 2) able to segment unknown cellular components, 3) fully unsupervised and does not rely on the availability of training data. As an important step towards this goal, in this paper, we propose a saliency detection method that computes the likelihood that a subregion in a tomogram stands out from the background. Our method consists of four steps: supervoxel over-segmentation, feature extraction, feature matrix decomposition, and computation of saliency. The method produces a distribution map that represents the regions' saliency in tomograms. Our experiments show that our method can successfully label most salient regions detected by a human observer, and able to filter out regions not containing cellular components. Therefore, our method can remove the majority of the background region, and significantly speed up the subsequent processing of segmentation and recognition of cellular components captured by ECT.