Drug–drug interactions (DDIs) prediction is a challenging task in drug development and clinical application. Due to the extremely large complete set of all possible DDIs, computer-aided DDIs prediction methods are getting lots of attention in the pharmaceutical industry and academia. However, most existing computational methods only use single perspective information and few of them conduct the task based on the biomedical knowledge graph (BKG), which can provide more detailed and comprehensive drug lateral side information flow. To this end, a deep learning framework, namely DeepLGF, is proposed to fully exploit BKG fusing local–global information to improve the performance of DDIs prediction. More specifically, DeepLGF first obtains chemical local information on drug sequence semantics through a natural language processing algorithm. Then a model of BFGNN based on graph neural network is proposed to extract biological local information on drug through learning embedding vector from different biological functional spaces. The global feature information is extracted from the BKG by our knowledge graph embedding method. In DeepLGF, for fusing local–global features well, we designed four aggregating methods to explore the most suitable ones. Finally, the advanced fusing feature vectors are fed into deep neural network to train and predict. To evaluate the prediction performance of DeepLGF, we tested our method in three prediction tasks and compared it with state-of-the-art models. In addition, case studies of three cancer-related and COVID-19-related drugs further demonstrated DeepLGF’s superior ability for potential DDIs prediction. The webserver of the DeepLGF predictor is freely available at http://120.77.11.78/DeepLGF/.

The way of co-administration of drugs is a sensible strategy for treating complex diseases efficiently. Because of existing massive unknown interactions among drugs, predicting potential adverse drug–drug interactions (DDIs) accurately is promotive to prevent unanticipated interactions, which may cause significant harm to patients. Currently, numerous computational studies are focusing on potential DDIs prediction on account of traditional experiments in wet lab being time-consuming, labor-consuming, costly and inaccurate. These approaches performed well; however, many approaches did not consider multi-scale features and have the limitation that they cannot predict interactions among novel drugs. In this paper, we proposed a model of BioDKG–DDI, which integrates multi-feature with biochemical information to predict potential DDIs through an attention machine with superior performance. Molecular structure features, representation of drug global association using drug knowledge graph (DKG) and drug functional similarity features are fused by attention machine and predicted through deep neural network. A novel negative selecting method is proposed to certify the robustness and stability of our method. Then, three datasets with different sizes are used to test BioDKG–DDI. Furthermore, the comparison experiments and case studies can demonstrate the reliability of our method. Upon our finding, BioDKG–DDI is a robust, yet simple method and can be used as a benefic supplement to the experimental process.

A large amount of clinical evidence began to mount, showing that circular ribonucleic acids (RNAs; circRNAs) perform a very important function in complex diseases by participating in transcription and translation regulation of microRNA (miRNA) target genes. However, with strict high-throughput techniques based on traditional biological experiments and the conditions and environment, the association between circRNA and miRNA can be discovered to be labor-intensive, expensive, time-consuming, and inefficient. In this paper, we proposed a novel computational model based on Word2vec, Structural Deep Network Embedding (SDNE), Convolutional Neural Network and Deep Neural Network, which predicts the potential circRNA-miRNA associations, called Word2vec, SDNE, Convolutional Neural Network and Deep Neural Network (WSCD). Specifically, the WSCD model extracts attribute feature and behaviour feature by word embedding and graph embedding algorithm, respectively, and ultimately feed them into a feature fusion model constructed by combining Convolutional Neural Network and Deep Neural Network to deduce potential circRNA-miRNA interactions. The proposed method is proved on dataset and obtained a prediction accuracy and an area under the receiver operating characteristic curve of 81.61% and 0.8898, respectively, which is shown to have much higher accuracy than the state-of-the-art models and classifier models in prediction. In addition, 23 miRNA-related circular RNAs (circRNAs) from the top 30 were confirmed in relevant experiences. In these works, all results represent that WSCD would be a helpful supplementary reliable method for predicting potential miRNA-circRNA associations compared to wet laboratory experiments.

Adverse drug-drug interaction events (DDIEs) pose serious risks to patient safety, yet rare but severe interactions remain challenging to identify due to limited clinical data. Existing computational methods rely heavily on abundant samples, failing to identify rare DDIEs. Here we introduce RareDDIE, a metric-based meta-learning model that employs a dual-granular structure-driven pair variational representation to enhance rare DDIE prediction. To further address the challenge of zero-shot DDIE identification, we develop the Biological Semantic Transferring (BST) module, integrating large-scale sentence embeddings to form the ZetaDDIE variant. Our model outperforms existing methods in few-sample and zero-sample settings. Furthermore, we verify that knowledge transfer from DDIE can improve drug synergy predictions, surpassing existing models. Case studies on antiplatelet activity reduction and non-small cell lung cancer drug synergy further illustrate the practical value of RareDDIE. By analyzing the meta-knowledge construction process, we provide interpretability into the model’s decision-making. This work establishes an effective computational framework for rare DDIE prediction, leveraging meta-learning and knowledge transfer to overcome key challenges in data-limited scenarios.

Computational prediction of miRNAs, diseases, and genes associated with circRNAs has important implications for circRNA research, as well as provides a reference for wet experiments to save costs and time. In this study, SGCNCMI, a computational model combining multimodal information and graph convolutional neural networks, combines node similarity to form node information and then predicts associated nodes using GCN with a distributive contribution mechanism. The model can be used not only to predict the molecular level of circRNA–miRNA interactions but also to predict circRNA–cancer and circRNA–gene associations. The AUCs of circRNA—miRNA, circRNA–disease, and circRNA–gene associations in the five-fold cross-validation experiment of SGCNCMI is 89.42%, 84.18%, and 82.44%, respectively. SGCNCMI is one of the few models in this field and achieved the best results. In addition, in our case study, six of the top ten relationship pairs with the highest prediction scores were verified in PubMed.

Biomedical network learning offers fresh prospects for expediting drug repositioning. However, traditional network architectures struggle to quantify the relationship between micro-scale drug spatial structures and corresponding macro-scale biomedical networks, limiting their ability to capture key pharmacological properties and complex biomedical information crucial for drug screening and therapeutic discovery. Moreover, challenges such as difficulty in capturing long-range dependencies hinder current network-based approaches. To address these limitations, we introduce the Spatial Hierarchical Network, modeling molecular 3D structures and biological associations into a unified network. We propose an end-to-end framework, SpHN-VDA, integrating spatial hierarchical information through triple attention mechanisms to enhance machine understanding of molecular functionality and improve the accuracy of virus-drug association identification. SpHN-VDA outperforms leading models across three datasets, particularly excelling in out-of-distribution and cold-start scenarios. It also exhibits enhanced robustness against data perturbation, ranging from 20% to 40%. It accurately identifies critical motifs for binding sites, even without protein residue annotations. Leveraging reliability of SpHN-VDA, we have identified 25 potential candidate drugs through gene expression analysis and CMap. Molecular docking experiments with the SARS-CoV-2 spike protein further corroborate the predictions. This research highlights the broad potential of SpHN-VDA to enhance drug repositioning and identify effective treatments for various diseases.