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Long non‐coding RNAs (lncRNAs) and microRNAs (miRNAs) are two typical types of non‐coding RNAs that interact and play important regulatory roles in many animal organisms. Exploring the unknown interactions between lncRNAs and miRNAs contributes to a better understanding of their functional involvement. Currently, studying the interactions between lncRNAs and miRNAs heavily relies on laborious biological experiments. Therefore, it is necessary to design a computational method for predicting lncRNA–miRNA interactions. In this work, we propose a method called MPGK‐LMI, which utilizes a graph attention network (GAT) to predict lncRNA–miRNA interactions in animals. First, we construct a meta‐path similarity matrix based on known lncRNA–miRNA interaction information. Then, we use GAT to aggregate the constructed meta‐path similarity matrix and the computed Gaussian kernel similarity matrix to update the feature matrix with neighbourhood information. Finally, a scoring module is used for prediction. By comparing with three state‐of‐the‐art algorithms, MPGK‐LMI achieves the best results in terms of performance, with AUC value of 0.9077, AUPR of 0.9327, ACC of 0.9080, F1‐score of 0.9143 and precision of 0.8739. These results validate the effectiveness and reliability of MPGK‐LMI. Additionally, we conduct detailed case studies to demonstrate the effectiveness and feasibility of our approach in practical applications. Through these empirical results, we gain deeper insights into the functional roles and mechanisms of lncRNA–miRNA interactions, providing significant breakthroughs and advancements in this field of research. In summary, our method not only outperforms others in terms of performance but also establishes its practicality and reliability in biological research through real‐case analysis, offering strong support and guidance for future studies and applications.

Drug-drug interaction (DDI) event prediction is a challenging problem, and accurate prediction of DDI events is critical to patient health and new drug development. Recently, many machine learning-based techniques have been proposed for predicting DDI events. However, most of the existing methods do not effectively integrate the multidimensional features of drugs and provide poor mitigation of noise to get effective feature information. To address these limitations, we propose a DDI-Transform neural network framework for DDI event prediction. In DDI-Transform, we design a drug structure information feature extraction module and a drug bind-protein feature extraction module to obtain multidimensional feature information. A stack of DDI-Transform layers in the DDI-Transform network module are then used for adaptive learning, thus adaptively selecting the effective feature information for prediction. The results show that DDI-Transform can accurately predict DDI events and outperform the state-of-the-art models. Results on different scale datasets confirm the robustness of the method.

Background Drug-target interaction (DTI) prediction has become a crucial prerequisite in drug design and drug discovery. However, the traditional biological experiment is time-consuming and expensive, as there are abundant complex interactions present in the large size of genomic and chemical spaces. For alleviating this phenomenon, plenty of computational methods are conducted to effectively complement biological experiments and narrow the search spaces into a preferred candidate domain. Whereas, most of the previous approaches cannot fully consider association behavior semantic information based on several schemas to represent complex the structure of heterogeneous biological networks. Additionally, the prediction of DTI based on single modalities cannot satisfy the demand for prediction accuracy. Methods We propose a multi-modal representation framework of ‘DeepMPF’ based on meta-path semantic analysis, which effectively utilizes heterogeneous information to predict DTI. Specifically, we first construct protein–drug-disease heterogeneous networks composed of three entities. Then the feature information is obtained under three views, containing sequence modality, heterogeneous structure modality and similarity modality. We proposed six representative schemas of meta-path to preserve the high-order nonlinear structure and catch hidden structural information of the heterogeneous network. Finally, DeepMPF generates highly representative comprehensive feature descriptors and calculates the probability of interaction through joint learning. Results To evaluate the predictive performance of DeepMPF, comparison experiments are conducted on four gold datasets. Our method can obtain competitive performance in all datasets. We also explore the influence of the different feature embedding dimensions, learning strategies and classification methods. Meaningfully, the drug repositioning experiments on COVID-19 and HIV demonstrate DeepMPF can be applied to solve problems in reality and help drug discovery. The further analysis of molecular docking experiments enhances the credibility of the drug candidates predicted by DeepMPF. Conclusions All the results demonstrate the effectively predictive capability of DeepMPF for drug-target interactions. It can be utilized as a useful tool to prescreen the most potential drug candidates for the protein. The web server of the DeepMPF predictor is freely available at http://120.77.11.78/DeepMPF/ , which can help relevant researchers to further study.

Background Drug discovery is known for the large amount of money and time it consumes and the high risk it takes. Drug repositioning has, therefore, become a popular approach to save time and cost by finding novel indications for approved drugs. In order to distinguish these novel indications accurately in a great many of latent associations between drugs and diseases, it is necessary to exploit abundant heterogeneous information about drugs and diseases. Results In this article, we propose a meta-path-based computational method called NEDD to predict novel associations between drugs and diseases using heterogeneous information. First, we construct a heterogeneous network as an undirected graph by integrating drug-drug similarity, disease-disease similarity, and known drug-disease associations. NEDD uses meta paths of different lengths to explicitly capture the indirect relationships, or high order proximity, within drugs and diseases, by which the low dimensional representation vectors of drugs and diseases are obtained. NEDD then uses a random forest classifier to predict novel associations between drugs and diseases. Conclusions The experiments on a gold standard dataset which contains 1933 validated drug–disease associations show that NEDD produces superior prediction results compared with the state-of-the-art approaches.

The current BERT-based question answering systems use a question and a contextual text to find the answer. This causes the systems to return wrong answers or nothing if the text contains irrelevant contents with the input question. Besides, the systems haven’t answered yes-no and aggregate questions yet. Besides that, the systems only concentrate on the contents of text regardless of the relationship between entities in the corpus. This systems cannot validate the answer. In this paper, we presented a solution to solve these issues by using the BERT model and the knowledge graph to enhance a question answering system. We combined content-based and linked-based information for knowledge graph representation learning and classified triples into one of three classes such as base class, derived class, or non-existent class. We then used the BERT model to build two classifiers: BERT-based text classification for content information and BERT-based triple classification for link information. The former was able to make a contextual embedding vector for representing triples that were used to classify into the three above classes. The latter generated all path instances from all meta paths of a large heterogeneous information network by running the Motif Search method of Apache Spark on a distributed environment. After creating the path instances, we produced triples from these path instances. We made content-based information by converting triples into natural language text with labels and considered them as a text classification problem. Our proposed solution outperformed other embedding methods with an average accuracy of 92.34% on benchmark datasets and the Motif Finding algorithm with an average executive time improvement of 37% on the distributed environment.

Background In the context of drug discovery, drug target interactions (DTIs) can be predicted based on observed topological features of a semantic network across the chemical and biological space. In a semantic network, the types of the nodes and links are different. In order to take into account the heterogeneity of the semantic network, meta-path-based topological patterns were investigated for link prediction. Results Supervised machine learning models were constructed based on meta-path topological features of an enriched semantic network, which was derived from Chem2Bio2RDF, and was expanded by adding compound and protein similarity neighboring links obtained from the PubChem databases. The additional semantic links significantly improved the predictive performance of the supervised learning models. The binary classification model built upon the enriched feature space using the Random Forest algorithm significantly outperformed an existing semantic link prediction algorithm, Semantic Link Association Prediction (SLAP), to predict unknown links between compounds and protein targets in an evolving network. In addition to link prediction, Random Forest also has an intrinsic feature ranking algorithm, which can be used to select the important topological features that contribute to link prediction. Conclusions The proposed framework has been demonstrated as a powerful alternative to SLAP in order to predict DTIs using the semantic network that integrates chemical, pharmacological, genomic, biological, functional, and biomedical information into a unified framework. It offers the flexibility to enrich the feature space by using different normalization processes on the topological features, and it can perform model construction and feature selection at the same time.

Background Drug repositioning is a very important task that provides critical information for exploring the potential efficacy of drugs. Yet developing computational models that can effectively predict drug–disease associations (DDAs) is still a challenging task. Previous studies suggest that the accuracy of DDA prediction can be improved by integrating different types of biological features. But how to conduct an effective integration remains a challenging problem for accurately discovering new indications for approved drugs. Methods In this paper, we propose a novel meta-path based graph representation learning model, namely RLFDDA, to predict potential DDAs on heterogeneous biological networks. RLFDDA first calculates drug–drug similarities and disease–disease similarities as the intrinsic biological features of drugs and diseases. A heterogeneous network is then constructed by integrating DDAs, disease–protein associations and drug–protein associations. With such a network, RLFDDA adopts a meta-path random walk model to learn the latent representations of drugs and diseases, which are concatenated to construct joint representations of drug–disease associations. As the last step, we employ the random forest classifier to predict potential DDAs with their joint representations. Results To demonstrate the effectiveness of RLFDDA, we have conducted a series of experiments on two benchmark datasets by following a ten-fold cross-validation scheme. The results show that RLFDDA yields the best performance in terms of AUC and F1-score when compared with several state-of-the-art DDAs prediction models. We have also conducted a case study on two common diseases, i.e., paclitaxel and lung tumors, and found that 7 out of top-10 diseases and 8 out of top-10 drugs have already been validated for paclitaxel and lung tumors respectively with literature evidence. Hence, the promising performance of RLFDDA may provide a new perspective for novel DDAs discovery over heterogeneous networks.

In the domain of heterogeneous graph representation learning, traditional methodologies often rely excessively on manually crafted meta-paths and neighbor aggregation mechanisms when faced with diverse node types and complex relationships. This dependence makes it challenging for models to adaptively optimize in situations of information scarcity or insufficient neighbors, frequently resulting in excessive information smoothing and inadequate representational capacity, which in turn affects the distinctiveness of node representations and the effectiveness of tasks. To address these limitations, this paper proposes a framework named GraphFlow, grounded in information flow optimization and potential neighbor selection mechanisms, with the aim of enhancing the learning of inter-node associations through optimized information propagation. Our framework transcends the conventional fixed reliance on neighbors by dynamically optimizing information flow paths and adaptively selecting potential neighbors, enabling it to flexibly and effectively capture latent yet highly relevant neighbors within the graph, even in contexts of information scarcity or a lack of direct neighbors. Specifically, by integrating HodgeRank ranking and adaptive meta-path generation, our approach not only effectively refines the neighbor selection process but also allows for the adaptive modeling of deep semantic relationships among nodes within a multi-level, multi-relational graph structure. This significantly enhances the distinctiveness of node representations and facilitates the effective dissemination of information flow. Extensive experiments conducted on multiple publicly available heterogeneous graph datasets validate that the proposed GraphFlow method outperforms the best baseline performances in tasks such as node classification and link prediction across most evaluation metrics. Notably, it demonstrates exceptional performance on heterogeneous graph datasets characterized by complex node types and multiple relationships, markedly improving the model’s distinctiveness and generalization capabilities.

The combinatorial therapy with multiple drugs may lead to unexpected drug-drug interactions (DDIs) and result in adverse reactions to patients. Predicting DDI events can mitigate the potential risks of combinatorial therapy and enhance drug safety. In recent years, deep models based on heterogeneous graph representation learning have attracted widespread interest in DDI event prediction and have yielded satisfactory results, but there is still room for improvement in prediction performance. In this study, we proposed a meta-path-based heterogeneous graph contrastive learning model, MPHGCL-DDI, for DDI event prediction. The model constructs two contrastive views based on meta-paths: an average graph view and an augmented graph view. The former represents that there are connections between drugs, while the latter reveals how the drugs connect with each other. We defined three levels of data augmentation schemes in the augmented graph view and adopted a combination of three losses in the model training phase: multi-relation prediction loss, unsupervised contrastive loss and supervised contrastive loss. Furthermore, the model incorporates indirect drug information, protein–protein interactions (PPIs), to reveal latent relations of drugs. We evaluated MPHGCL-DDI on three different tasks of two datasets. Experimental results demonstrate that MPHGCL-DDI surpasses several state-of-the-art methods in performance.

Accurately predicting Drug-Disease Associations (DDAs) is of great significance for drug repurposing and new drug development. Although existing methods have promoted the development of this field to a certain extent, most of them are still limited to single-modal data and cannot fully characterize the complex features of drugs, diseases, and genes. At the same time, many methods only focus on either local neighborhoods or global structures during feature extraction, lacking the organic combination of the two, which limits the accuracy and generalization of predictions. To address this, this paper proposes MedPathEx, a drug-disease association prediction method that combines multi-modal data integration and local-global feature learning. Specifically, we first construct a drug-gene-disease heterogeneous network and fuse multi-modal attributes such as drug chemical structures, ATC classifications, side effects, disease phenotypes and semantic information, as well as gene function annotations to generate more comprehensive node representations. Subsequently, we use graph convolutional networks to extract the attribute features of nodes themselves, capture local semantic relationships through meta-path modeling with a multi-head attention mechanism, and introduce a global attention mechanism to extract overall topological patterns, thereby achieving “micro-macro complementary” feature learning. Finally, by fusing node attributes and structural features, MedPathEx obtains a more discriminative comprehensive representation for the prediction of potential DDAs. Experimental results show that MedPathEx outperforms existing methods in key indicators such as AUC, AP, and F1. Moreover, it successfully identifies new candidate drugs in cases of coronary artery disease and hypertension, demonstrating its great potential in practical applications.