Accurate prediction of Drug-Target Affinity (DTA) is crucial for reducing experimental costs and accelerating early screening in computational drug discovery. While sequence-based deep learning methods avoid reliance on costly 3D structures, they still overlook simultaneous modeling of global sequence semantic features and local topological structural features within drugs and proteins, and represent drugs as flat sequences without atomic-level, substructural-level, and molecular-level multi-scale features. We propose HiF-DTA, a hierarchical network that adopts a dual-pathway strategy to extract both global sequence semantic and local topological features from drug and protein sequences, and models drugs multi-scale to learn atomic, substructural, and molecular representations fused via a multiscale bilinear attention module. Experiments on Davis, KIBA, and Metz datasets show HiF-DTA outperforms state-of-the-art baselines, with ablations confirming the importance of globallocal extraction and multi-scale fusion.

Positron emission tomography (PET) is a nuclear medical imaging technique where image quality depends on the dose of radionuclides administered to the patient. While standard-dose PET (SPET) offers high-quality imaging, it also poses radiation risks. If reconstructing low-dose PET (LPET) images can guarantee the same level of imaging quality, LPET could serve as a safer alternative by reducing patient radiation exposure. Recent approaches using convolutional neural networks (CNNs) struggle to capture complex features of LPET images due to the fixed convolutional kernels and local receptive fields. Generative adversarial network (GAN)-based methods may suffer from mode collapse and unstable training. Diffusion model-based works can ensure stability and high-quality sample generation but come with high computational costs. Furthermore, all these methods focus solely on spatial domain information, neglecting crucial frequency domain information.To address these issues, we propose an efficient residual-based LPET reconstruction framework combining CNN and diffusion model. Our framework includes a multi-scale dynamic convolution network with a wavelet reconstruction module (MN-WR) to leverage multi-scale spatial and frequency domain information. We also introduce a residual-based diffusion model (ReD) to enhance local detail reconstruction while reducing computational costs. Finally, we design a wavelet-based frequency domain fusion (WFF) module to combine low-frequency edge information from MN-WR with high-frequency details from ReD. Experimental results on public LPET datasets show that our method outperforms state-of-the-art techniques and significantly reduces computational costs. Code is available at https://github.com/TAI-Medical-Lab/LPET-Reconstruction.

While deep learning models play a crucial role in predicting antibody-antigen interactions (AAI), the scarcity of publicly available sequence-structure pairings constrains their generalization. Current AAI methods often focus on residue-level static details, overlooking fine-grained structural representations of antibodies and their inter-antibody similarities. To tackle this challenge, we introduce a multi-modality representation approach that integates 3D structural and 1D sequence data to unravel intricate intra-antibody hierarchical relationships. By harnessing these representations, we present MuLAAIP, an AAI prediction framework that utilizes graph attention networks to illuminate graph-level structural features and normalized adaptive graph convolution networks to capture inter-antibody sequence associations. Furthermore, we have curated an AAI benchmark dataset comprising both structural and sequence information along with interaction labels. Through extensive experiments on this benchmark, our results demonstrate that MuLAAIP outperforms current state-of-the-art methods in terms of predictive performance. The implementation code and dataset are publicly available at https://github.com/trashTian/MuLAAIP for reproducibility.

MOTIVATION: Predicting the binding affinity between antigens and antibodies accurately is crucial for assessing therapeutic antibody effectiveness and enhancing antibody engineering and vaccine design. Traditional machine learning methods have been widely used for this purpose, relying on interfacial amino acids' structural information. Nevertheless, due to technological limitations and high costs of acquiring structural data, the structures of most antigens and antibodies are unknown, and sequence-based methods have gained attention. Existing sequence-based approaches designed for protein-protein affinity prediction exhibit a significant drop in performance when applied directly to antibody-antigen affinity prediction due to imbalanced training data and lacking design in the model framework specifically for antibody-antigen, hindering the learning of key features of antibodies and antigens. Therefore, we propose MVSF-AB, a Multi-View Sequence Feature learning for accurate Antibody-antigen Binding affinity prediction. RESULTS: MVSF-AB designs a multi-view method that fuses semantic features and residue features to fully utilize the sequence information of antibody-antigen and predicts the binding affinity. Experimental results demonstrate that MVSF-AB outperforms existing approaches in predicting unobserved natural antibody-antigen affinity and maintains its effectiveness when faced with mutant strains of antibodies. AVAILABILITY AND IMPLEMENTATION: Datasets we used and source code are available on our public GitHub repository https://github.com/TAI-Medical-Lab/MVSF-AB.

Collaborative learning (CL) is a distributed learning framework that aims to protect user privacy by allowing users to jointly train a model by sharing their gradient updates only. However, gradient inversion attacks (GIAs), which recover users' training data from shared gradients, impose severe privacy threats to CL. Existing defense methods adopt different techniques, e.g., differential privacy, cryptography, and perturbation defenses, to defend against the GIAs. Nevertheless, all current defense methods suffer from a poor trade-off between privacy, utility, and efficiency. To mitigate the weaknesses of existing solutions, we propose a novel defense method, Dual Gradient Pruning (DGP), based on gradient pruning, which can improve communication efficiency while preserving the utility and privacy of CL. Specifically, DGP slightly changes gradient pruning with a stronger privacy guarantee. And DGP can also significantly improve communication efficiency with a theoretical analysis of its convergence and generalization. Our extensive experiments show that DGP can effectively defend against the most powerful GIAs and reduce the communication cost without sacrificing the model's utility.

Drug-target interaction is fundamental in understanding how drugs affect biological systems, and accurately predicting drug-target affinity (DTA) is vital for drug discovery. Recently, deep learning methods have emerged as a significant approach for estimating the binding strength between drugs and target proteins. However, existing methods simply utilize the drug’s local information from molecular topology rather than global information. Additionally, the features of drugs and proteins are usually fused with a simple concatenation operation, limiting their effectiveness. To address these challenges, we proposed ViDTA, an enhanced DTA prediction framework. We introduce virtual nodes into the Graph Neural Network (GNN)-based drug feature extraction network, which acts as a global memory to exchange messages more efficiently. By incorporating virtual graph nodes, we seamlessly integrate local and global features of drug molecular structures, expanding the GNN’s receptive field. Additionally, we propose an attention-based linear feature fusion network for better capturing the interaction information between drugs and proteins. Experimental results evaluated on various benchmarks including Davis, Metz, and KIBA demonstrate that our proposed ViDTA outperforms the state-of-the-art baselines.