Yang Liu

Xiangzhe Kong, Wenbing Huang, Yang Liu

Antibody design is valuable for therapeutic usage and biological research. Existing deep-learning-based methods encounter several key issues: 1) incomplete context for Complementarity-Determining Regions (CDRs) generation; 2) incapability of capturing the entire 3D geometry of the input structure; 3) inefficient prediction of the CDR sequences in an autoregressive manner. In this paper, we propose Multi-channel Equivariant Attention Network (MEAN) to co-design 1D sequences and 3D structures of CDRs. To be specific, MEAN formulates antibody design as a conditional graph translation problem by importing extra components including the target antigen and the light chain of the antibody. Then, MEAN resorts to E(3)-equivariant message passing along with a proposed attention mechanism to better capture the geometrical correlation between different components. Finally, it outputs both the 1D sequences and 3D structure via a multi-round progressive full-shot scheme, which enjoys more efficiency and precision against previous autoregressive approaches. Our method significantly surpasses state-of-the-art models in sequence and structure modeling, antigen-binding CDR design, and binding affinity optimization. Specifically, the relative improvement to baselines is about 23% in antigen-binding CDR design and 34% for affinity optimization.

Xiangzhe Kong, Wenbing Huang, Yang Liu

Antibody design is an essential yet challenging task in various domains like therapeutics and biology. There are two major defects in current learning-based methods: 1) tackling only a certain subtask of the whole antibody design pipeline, making them suboptimal or resource-intensive. 2) omitting either the framework regions or side chains, thus incapable of capturing the full-atom geometry. To address these pitfalls, we propose dynamic Multi-channel Equivariant grAph Network (dyMEAN), an end-to-end full-atom model for E(3)-equivariant antibody design given the epitope and the incomplete sequence of the antibody. Specifically, we first explore structural initialization as a knowledgeable guess of the antibody structure and then propose shadow paratope to bridge the epitope-antibody connections. Both 1D sequences and 3D structures are updated via an adaptive multi-channel equivariant encoder that is able to process protein residues of variable sizes when considering full atoms. Finally, the updated antibody is docked to the epitope via the alignment of the shadow paratope. Experiments on epitope-binding CDR-H3 design, complex structure prediction, and affinity optimization demonstrate the superiority of our end-to-end framework and full-atom modeling.

Ziyang Yu, Wenbing Huang, Yang Liu

The study of rigid protein-protein docking plays an essential role in a variety of tasks such as drug design and protein engineering. Recently, several learning-based methods have been proposed for the task, exhibiting much faster docking speed than those computational methods. In this paper, we propose a novel learning-based method called ElliDock, which predicts an elliptic paraboloid to represent the protein-protein docking interface. To be specific, our model estimates elliptic paraboloid interfaces for the two input proteins respectively, and obtains the roto-translation transformation for docking by making two interfaces coincide. By its design, ElliDock is independently equivariant with respect to arbitrary rotations/translations of the proteins, which is an indispensable property to ensure the generalization of the docking process. Experimental evaluations show that ElliDock achieves the fastest inference time among all compared methods and is strongly competitive with current state-of-the-art learning-based models such as DiffDock-PP and Multimer particularly for antibody-antigen docking.

Shanlin Sun, Yang Liu, Narisu Bai et al.

Organs-at-risk (OAR) delineation in computed tomography (CT) is an important step in Radiation Therapy (RT) planning. Recently, deep learning based methods for OAR delineation have been proposed and applied in clinical practice for separate regions of the human body (head and neck, thorax, and abdomen). However, there are few researches regarding the end-to-end whole-body OARs delineation because the existing datasets are mostly partially or incompletely annotated for such task. In this paper, our proposed end-to-end convolutional neural network model, called \textbf{AttentionAnatomy}, can be jointly trained with three partially annotated datasets, segmenting OARs from whole body. Our main contributions are: 1) an attention module implicitly guided by body region label to modulate the segmentation branch output; 2) a prediction re-calibration operation, exploiting prior information of the input images, to handle partial-annotation(HPA) problem; 3) a new hybrid loss function combining batch Dice loss and spatially balanced focal loss to alleviate the organ size imbalance problem. Experimental results of our proposed framework presented significant improvements in both Sørensen-Dice coefficient (DSC) and 95\% Hausdorff distance compared to the baseline model.