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.

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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.

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.