DeepOrientation: Deep Orientation Estimation of Macromolecules in Cryo-electron tomography

Abstract Orientation estimation of macromolecules in cryo-electron tomography (cryo-ET) images is one of the fundamental steps in applying subtomogram averaging. The standard method in particle picking and orientation estimation is template matching (TM), which is computationally very expensive, with its performance depending linearly on the number of template orientations. In addition to conventional image processing methods like TM, the investigation of crowded cell environments using cryo-ET has also been attempted with deep learning (DL) methods. These attempts were restricted to macromolecule localization and identification while orientation estimation was not addressed due to a lack of a large enough dataset of ground truth annotations suitable for DL. To this end, we first generate a large-scale synthetic dataset of 450 tomograms containing almost 200K samples of two macromolecular structures using the PolNet simulator. Utilizing this synthetic dataset, we address the problem of particle orientation estimation as a regression problem by proposing a DL-based model based on multi-layer perceptron networks and a six-degree-of-freedom orientation representation. The iso-surface visualizations of the averaged subtomograms show that the predicted results by the network are overly similar to that of ground truth. Our work shows that orientation estimation of particles using DL methods is in principle possible provided that ground truth data is available. What remains to be solved is the gap between synthetic and experimental data. The source code is available at https://github.com/noushinha/DeepOrientation. Competing Interest Statement The authors have declared no competing interest. Footnotes Dear Editors, We noticed the order of the authors in the Author List is different from that of the paper which is corrected now. In addition, there was a typo in the abstract where the word "perception" is now replaced with "perceptron". Regards, Noushin https://www.zib.de/ext-data/PolNet_Medium_Size_Dataset_4v4r_and_3j9i.zip