Gum-Net: Unsupervised Geometric Matching for Fast and Accurate 3D Subtomogram Image Alignment and Averaging

We propose a Geometric unsupervised matching Network (Gum-Net) for finding the geometric correspondence between two images with application to 3D subtomogram alignment and averaging. Subtomogram alignment is the most important task in cryo-electron tomography (cryo-ET), a revolutionary 3D imaging technique for visualizing the molecular organization of unperturbed cellular landscapes in single cells. However, subtomogram alignment and averaging are very challenging due to severe imaging limits such as noise and missing wedge effects. We introduce an end-to-end trainable architecture with three novel modules specifically designed for preserving feature spatial information and propagating feature matching information. The training is performed in a fully unsupervised fashion to optimize a matching metric. No ground truth transformation information nor category-level or instance-level matching supervision information is needed. After systematic assessments on six real and nine simulated datasets, we demonstrate that Gum-Net reduced the alignment error by 40 to 50% and improved the averaging resolution by 10%. Gum-Net also achieved 70 to 110 times speedup in practice with GPU acceleration compared to state-of-the-art subtomogram alignment methods. Our work is the first 3D unsupervised geometric matching method for images of strong transformation variation and high noise level. The training code, trained model, and datasets are available in our open-source software AITom.