The properties of the drug may be altered by the combination, which may cause unexpected drug–drug interactions (DDIs). Prediction of DDIs provides combination strategies of drugs for systematic and effective treatment. In most of deep learning-based methods for predicting DDI, encoded information about the drugs is insufficient in some extent, which limits the performances of DDIs prediction. In this work, we propose a novel attention-mechanism-based multidimensional feature encoder for DDIs prediction, namely attention-based multidimensional feature encoder (AMDE). Specifically, in AMDE, we encode drug features from multiple dimensions, including information from both Simplified Molecular-Input Line-Entry System sequence and atomic graph of the drug. Data experiments are conducted on DDI data set selected from Drugbank, involving a total of 34 282 DDI relationships with 17 141 positive DDI samples and 17 141 negative samples. Experimental results show that our AMDE performs better than some state-of-the-art baseline methods, including Random Forest, One-Dimension Convolutional Neural Networks, DeepDrug, Long Short-Term Memory, Seq2seq, Deepconv, DeepDDI, Graph Attention Networks and Knowledge Graph Neural Networks. In practice, we select a set of 150 drugs with 3723 DDIs, which are never appeared in training, validation and test sets. AMDE performs well in DDIs prediction task, with AUROC and AUPRC 0.981 and 0.975. As well, we use Torasemide (DB00214) as an example and predict the most likely drug to interact with it. The top 15 scores all have been reported with clear interactions in literatures.

Multi-drug combinations for the treatment of complex diseases are gradually becoming an important treatment, and this type of treatment can take advantage of the synergistic effects among drugs. However, drug–drug interactions (DDIs) are not just all beneficial. Accurate and rapid identifications of the DDIs are essential to enhance the effectiveness of combination therapy and avoid unintended side effects. Traditional DDIs prediction methods use only drug sequence information or drug graph information, which ignores information about the position of atoms and edges in the spatial structure. In this paper, we propose Molormer, a method based on a lightweight attention mechanism for DDIs prediction. Molormer takes the two-dimension (2D) structures of drugs as input and encodes the molecular graph with spatial information. Besides, Molormer uses lightweight-based attention mechanism and self-attention distilling to process spatially the encoded molecular graph, which not only retains the multi-headed attention mechanism but also reduces the computational and storage costs. Finally, we use the Siamese network architecture to serve as the architecture of Molormer, which can make full use of the limited data to train the model for better performance and also limit the differences to some extent between networks dealing with drug features. Experiments show that our proposed method outperforms state-of-the-art methods in Accuracy, Precision, Recall and F1 on multi-label DDIs dataset. In the case study section, we used Molormer to make predictions of new interactions for the drugs Aliskiren, Selexipag and Vorapaxar and validated parts of the predictions. Code and models are available at https://github.com/IsXudongZhang/Molormer.

Liver cancer is one of the most common malignant diseases worldwide. Segmentation and reconstruction of liver tumors and vessels in CT images can provide convenience for physicians in preoperative planning and surgical intervention. In this paper, we introduced a TransFusionNet framework, which consists of a semantic feature extraction module, a local spatial feature extraction module, an edge feature extraction module, and a multi-scale feature fusion module to achieve fine-grained segmentation of liver tumors and vessels. In addition, we applied the transfer learning approach to pre-train using public datasets and then fine-tune the model to further improve the fitting effect. Furthermore, we proposed an intelligent quantization scheme to compress the model weights and achieved high performance inference on JetsonTX2. The TransFusionNet framework achieved mean IoU of 0.854 in vessel segmentation task, and achieved mean IoU of 0.927 in liver tumor segmentation task. When profiling the Computational Performance of the quantized inference, our quantized model achieved 4TFLOPs on Node with NVIDIA RTX3090 and 132GFLOPs on JetsonTX2. This unprecedented segmentation effect solves the accuracy and performance bottleneck of automated segmentation to a certain extent.

Cancer prognosis is an essential goal for early diagnosis, biomarker selection, and medical therapy. In the past decade, deep learning has successfully solved a variety of biomedical problems. However, due to the high dimensional limitation of human cancer transcriptome data and the small number of training samples, there is still no mature deep learning-based survival analysis model that can completely solve problems in the training process like overfitting and accurate prognosis. Given these problems, we introduced a novel framework called SAVAE-Cox for survival analysis of high-dimensional transcriptome data. This model adopts a novel attention mechanism and takes full advantage of the adversarial transfer learning strategy. We trained the model on 16 types of TCGA cancer RNA-seq data sets. Experiments show that our module outperformed state-of-the-art survival analysis models such as the Cox proportional hazard model (Cox-ph), Cox-lasso, Cox-ridge, Cox-nnet, and VAECox on the concordance index. In addition, we carry out some feature analysis experiments. Based on the experimental results, we concluded that our model is helpful for revealing cancer-related genes and biological functions.

Current structure-based molecular generation faces a fundamental dilemma: While static ligand modeling dominates computational approaches, real-world molecular interactions are inherently dynamic. Inspired by the conformational changes ligands undergo during semi-flexible docking, we propose a reinforcement learning (RL)–steered diffusion framework for semi-flexible molecular generation in protein pockets. By defining the denoising process as a Markov decision process, RL dynamically adjusts molecular structures through iterative exploration. Simultaneously, we incorporate multiple molecular properties as conditions to constrain the denoising policy to drug-like regions and perform self-supervised rigid training on both target-free and target-specific molecules. In addition, we propose a fast sampling strategy that accelerates sampling by 20 times, thereby improving the efficiency of training and sampling. Experiments demonstrate that our method outperforms state-of-the-art methods with a Vina score of −7.23 kcal/mol and an 11.53% success rate. Targeting unseen real-world proteins, the generated molecules preserve canonical interaction patterns while discovering previously unknown binding chemotypes.