No abstract

Cellular processes are governed by macromolecular complexes inside the cell. Study of the native structures of macromolecular complexes has been extremely difficult due to lack of data. With recent breakthroughs in Cellular Electron Cryo-Tomography (CECT) 3D imaging technology, it is now possible for researchers to gain accesses to fully study and understand the macro-molecular structures single cells. However, systematic recovery of macromolecular structures from CECT is very difficult due to high degree of structural complexity and practical imaging limitations. Specifically, we proposed a deep learning-based image classification approach for large-scale systematic macromolecular structure separation from CECT data. However, our previous work was only a very initial step toward exploration of the full potential of deep learning-based macromolecule separation. In this paper, we focus on improving classification performance by proposing three newly designed individual CNN models: an extended version of (Deep Small Receptive Field) DSRF3D, donated as DSRF3D-v2, a 3D residual block-based neural network, named as RB3D, and a convolutional 3D (C3D)-based model, CB3D. We compare them with our previously developed model (DSRF3D) on 12 datasets with different SNRs and tilt angle ranges. The experiments show that our new models achieved significantly higher classification accuracies. The accuracies are not only higher than 0.9 on normal datasets, but also demonstrate potentials to operate on datasets with high levels of noises and missing wedge effects presented.

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.

The rapid advances of omics technologies have generated abundant genomic data in public repositories and effective analytical approaches are critical to fully decipher biological knowledge inside these data. Meta-analysis combines multiple studies of a related hypothesis to improve statistical power, accuracy and reproducibility beyond individual study analysis. To date, many transcriptomic meta-analysis methods have been developed, yet few thoughtful guidelines exist. Here, we introduce a comprehensive analytical pipeline and browser-based software suite, called MetaOmics, to meta-analyze multiple transcriptomic studies for various biological purposes, including quality control, differential expression analysis, pathway enrichment analysis, differential coexpression network analysis, prediction, clustering and dimension reduction. The pipeline includes many public as well as >10 in-house transcriptomic metaanalytic methods with data-driven and biological-aim-driven strategies, hands-on protocols, an intuitive user interface and step-by-step instructions.

Background Cryo-electron tomography (cryo-ET) enables the 3D visualization of cellular organization in near-native state which plays important roles in the field of structural cell biology. However, due to the low signal-to-noise ratio (SNR), large volume and high content complexity within cells, it remains difficult and time-consuming to localize and identify different components in cellular cryo-ET. To automatically localize and recognize in situ cellular structures of interest captured by cryo-ET, we proposed a simple yet effective automatic image analysis approach based on Faster-RCNN. Results Our experimental results were validated using in situ cyro-ET-imaged mitochondria data. Our experimental results show that our algorithm can accurately localize and identify important cellular structures on both the 2D tilt images and the reconstructed 2D slices of cryo-ET. When ran on the mitochondria cryo-ET dataset, our algorithm achieved Average Precision >0.95. Moreover, our study demonstrated that our customized pre-processing steps can further improve the robustness of our model performance. Conclusions In this paper, we proposed an automatic Cryo-ET image analysis algorithm for localization and identification of different structure of interest in cells, which is the first Faster-RCNN based method for localizing an cellular organelle in Cryo-ET images and demonstrated the high accuracy and robustness of detection and classification tasks of intracellular mitochondria. Furthermore, our approach can be easily applied to detection tasks of other cellular structures as well.