BJLD-CMI: a predictive circRNA-miRNA interactions model combining multi-angle feature information.

Increasing research findings suggest that circular RNA (circRNA) exerts a crucial function in the pathogenesis of complex human diseases by binding to miRNA. Identifying their potential interactions is of paramount importance for the diagnosis and treatment of diseases. However, long cycles, small scales, and time-consuming processes characterize previous biological wet experiments. Consequently, the use of an efficient computational model to forecast the interactions between circRNA and miRNA is gradually becoming mainstream. In this study, we present a new prediction model named BJLD-CMI. The model extracts circRNA sequence features and miRNA sequence features by applying Jaccard and Bert's method and organically integrates them to obtain CMI attribute features, and then uses the graph embedding method Line to extract CMI behavioral features based on the known circRNA-miRNA correlation graph information. And then we predict the potential circRNA-miRNA interactions by fusing the multi-angle feature information such as attribute and behavior through Autoencoder in Autoencoder Networks. BJLD-CMI attained 94.95% and 90.69% of the area under the ROC curve on the CMI-9589 and CMI-9905 datasets. When compared with existing models, the results indicate that BJLD-CMI exhibits the best overall competence. During the case study experiment, we conducted a PubMed literature search to confirm that out of the top 10 predicted CMIs, seven pairs did indeed exist. These results suggest that BJLD-CMI is an effective method for predicting interactions between circRNAs and miRNAs. It provides a valuable candidate for biological wet experiments and can reduce the burden of researchers.

Biolinguistic graph fusion model for circRNA-miRNA association prediction.

Emerging clinical evidence suggests that sophisticated associations with circular ribonucleic acids (RNAs) (circRNAs) and microRNAs (miRNAs) are a critical regulatory factor of various pathological processes and play a critical role in most intricate human diseases. Nonetheless, the above correlations via wet experiments are error-prone and labor-intensive, and the underlying novel circRNA-miRNA association (CMA) has been validated by numerous existing computational methods that rely only on single correlation data. Considering the inadequacy of existing machine learning models, we propose a new model named BGF-CMAP, which combines the gradient boosting decision tree with natural language processing and graph embedding methods to infer associations between circRNAs and miRNAs. Specifically, BGF-CMAP extracts sequence attribute features and interaction behavior features by Word2vec and two homogeneous graph embedding algorithms, large-scale information network embedding and graph factorization, respectively. Multitudinous comprehensive experimental analysis revealed that BGF-CMAP successfully predicted the complex relationship between circRNAs and miRNAs with an accuracy of 82.90% and an area under receiver operating characteristic of 0.9075. Furthermore, 23 of the top 30 miRNA-associated circRNAs of the studies on data were confirmed in relevant experiences, showing that the BGF-CMAP model is superior to others. BGF-CMAP can serve as a helpful model to provide a scientific theoretical basis for the study of CMA prediction.

Likelihood-based feature representation learning combined with neighborhood information for predicting circRNA-miRNA associations.

Connections between circular RNAs (circRNAs) and microRNAs (miRNAs) assume a pivotal position in the onset, evolution, diagnosis and treatment of diseases and tumors. Selecting the most potential circRNA-related miRNAs and taking advantage of them as the biological markers or drug targets could be conducive to dealing with complex human diseases through preventive strategies, diagnostic procedures and therapeutic approaches. Compared to traditional biological experiments, leveraging computational models to integrate diverse biological data in order to infer potential associations proves to be a more efficient and cost-effective approach. This paper developed a model of Convolutional Autoencoder for CircRNA-MiRNA Associations (CA-CMA) prediction. Initially, this model merged the natural language characteristics of the circRNA and miRNA sequence with the features of circRNA-miRNA interactions. Subsequently, it utilized all circRNA-miRNA pairs to construct a molecular association network, which was then fine-tuned by labeled samples to optimize the network parameters. Finally, the prediction outcome is obtained by utilizing the deep neural networks classifier. This model innovatively combines the likelihood objective that preserves the neighborhood through optimization, to learn the continuous feature representation of words and preserve the spatial information of two-dimensional signals. During the process of 5-fold cross-validation, CA-CMA exhibited exceptional performance compared to numerous prior computational approaches, as evidenced by its mean area under the receiver operating characteristic curve of 0.9138 and a minimal SD of 0.0024. Furthermore, recent literature has confirmed the accuracy of 25 out of the top 30 circRNA-miRNA pairs identified with the highest CA-CMA scores during case studies. The results of these experiments highlight the robustness and versatility of our model.

Genetically Encoded Lizard Color Divergence for Camouflage and Thermoregulation.

Local adaptation is critical in speciation and evolution, yet comprehensive studies on proximate and ultimate causes of local adaptation are generally scarce. Here, we integrated field ecological experiments, genome sequencing, and genetic verification to demonstrate both driving forces and molecular mechanisms governing local adaptation of body coloration in a lizard from the Qinghai-Tibet Plateau. We found dark lizards from the cold meadow population had lower spectrum reflectance but higher melanin contents than light counterparts from the warm dune population. Additionally, the colorations of both dark and light lizards facilitated the camouflage and thermoregulation in their respective microhabitat simultaneously. More importantly, by genome resequencing analysis, we detected a novel mutation in Tyrp1 that underpinned this color adaptation. The allele frequencies at the site of SNP 459# in the gene of Tyrp1 are 22.22% G/C and 77.78% C/C in dark lizards and 100% G/G in light lizards. Model-predicted structure and catalytic activity showed that this mutation increased structure flexibility and catalytic activity in enzyme TYRP1, and thereby facilitated the generation of eumelanin in dark lizards. The function of the mutation in Tyrp1 was further verified by more melanin contents and darker coloration detected in the zebrafish injected with the genotype of Tyrp1 from dark lizards. Therefore, our study demonstrates that a novel mutation of a major melanin-generating gene underpins skin color variation co-selected by camouflage and thermoregulation in a lizard. The resulting strong selection may reinforce adaptive genetic divergence and enable the persistence of adjacent populations with distinct body coloration.

MHESMMR: a multilevel model for predicting the regulation of miRNAs expression by small molecules.

According to the expression of miRNA in pathological processes, miRNAs can be divided into oncogenes or tumor suppressors. Prediction of the regulation relations between miRNAs and small molecules (SMs) becomes a vital goal for miRNA-target therapy. But traditional biological approaches are laborious and expensive. Thus, there is an urgent need to develop a computational model. In this study, we proposed a computational model to predict whether the regulatory relationship between miRNAs and SMs is up-regulated or down-regulated. Specifically, we first use the Large-scale Information Network Embedding (LINE) algorithm to construct the node features from the self-similarity networks, then use the General Attributed Multiplex Heterogeneous Network Embedding (GATNE) algorithm to extract the topological information from the attribute network, and finally utilize the Light Gradient Boosting Machine (LightGBM) algorithm to predict the regulatory relationship between miRNAs and SMs. In the fivefold cross-validation experiment, the average accuracies of the proposed model on the SM2miR dataset reached 79.59% and 80.37% for up-regulation pairs and down-regulation pairs, respectively. In addition, we compared our model with another published model. Moreover, in the case study for 5-FU, 7 of 10 candidate miRNAs are confirmed by related literature. Therefore, we believe that our model can promote the research of miRNA-targeted therapy.

SiSGC: A Drug Repositioning Prediction Model Based on Heterogeneous Simplifying Graph Convolution.

Drug repositioning plays a key role in disease treatment. With the large-scale chemical data increasing, many computational methods are utilized for drug-disease association prediction. However, most of the existing models neglect the positive influence of non-Euclidean data and multisource information, and there is still a critical issue for graph neural networks regarding how to set the feature diffuse distance. To solve the problems, we proposed SiSGC, which makes full use of the biological knowledge information as initial features and learns the structure information from the constructed heterogeneous graph with the adaptive selection of the information diffuse distance. Then, the structural features are fused with the denoised similarity information and fed to the advanced classifier of CatBoost to make predictions. Three different data sets are used to confirm the robustness and generalization of SiSGC under two splitting strategies. Experiment results demonstrate that the proposed model achieves superior performance compared with the six leading methods and four variants. Our case study on breast neoplasms further indicates that SiSGC is trustworthy and robust yet simple. We also present four drugs for breast cancer treatment with high confidence and further give an explanation for demonstrating the rationality. There is no doubt that SiSGC can be used as a beneficial supplement for drug repositioning.

An efficient circRNA-miRNA interaction prediction model by combining biological text mining and wavelet diffusion-based sparse network structure embedding.

MOTIVATION: Accumulating clinical evidence shows that circular RNA (circRNA) plays an important regulatory role in the occurrence and development of human diseases, which is expected to provide a new perspective for the diagnosis and treatment of related diseases. Using computational methods can provide high probability preselection for wet experiments to save resources. However, due to the lack of neighborhood structure in sparse biological networks, the model based on network embedding and graph embedding is difficult to achieve ideal results. RESULTS: In this paper, we propose BioDGW-CMI, which combines biological text mining and wavelet diffusion-based sparse network structure embedding to predict circRNA-miRNA interaction (CMI). In detail, BioDGW-CMI first uses the Bidirectional Encoder Representations from Transformers (BERT) for biological text mining to mine hidden features in RNA sequences, then constructs a CMI network, obtains the topological structure embedding of nodes in the network through heat wavelet diffusion patterns. Next, the Denoising autoencoder organically combines the structural features and Gaussian kernel similarity, finally, the feature is sent to lightGBM for training and prediction. BioDGW-CMI achieves the highest prediction performance in all three datasets in the field of CMI prediction. In the case study, all the 8 pairs of CMI based on circ-ITCH were successfully predicted. AVAILABILITY: The data and source code can be found at https://github.com/1axin/BioDGW-CMI-model.

DeepCMI: a graph-based model for accurate prediction of circRNA-miRNA interactions with multiple information.

Recently, the role of competing endogenous RNAs in regulating gene expression through the interaction of microRNAs has been closely associated with the expression of circular RNAs (circRNAs) in various biological processes such as reproduction and apoptosis. While the number of confirmed circRNA-miRNA interactions (CMIs) continues to increase, the conventional in vitro approaches for discovery are expensive, labor intensive, and time consuming. Therefore, there is an urgent need for effective prediction of potential CMIs through appropriate data modeling and prediction based on known information. In this study, we proposed a novel model, called DeepCMI, that utilizes multi-source information on circRNA/miRNA to predict potential CMIs. Comprehensive evaluations on the CMI-9905 and CMI-9589 datasets demonstrated that DeepCMI successfully infers potential CMIs. Specifically, DeepCMI achieved AUC values of 90.54% and 94.8% on the CMI-9905 and CMI-9589 datasets, respectively. These results suggest that DeepCMI is an effective model for predicting potential CMIs and has the potential to significantly reduce the need for downstream in vitro studies. To facilitate the use of our trained model and data, we have constructed a computational platform, which is available at http://120.77.11.78/DeepCMI/. The source code and datasets used in this work are available at https://github.com/LiYuechao1998/DeepCMI.

BCMCMI: A Fusion Model for Predicting circRNA-miRNA Interactions Combining Semantic and Meta-path.

More and more evidence suggests that circRNA plays a vital role in generating and treating diseases by interacting with miRNA. Therefore, accurate prediction of potential circRNA-miRNA interaction (CMI) has become urgent. However, traditional wet experiments are time-consuming and costly, and the results will be affected by objective factors. In this paper, we propose a computational model BCMCMI, which combines three features to predict CMI. Specifically, BCMCMI utilizes the bidirectional encoding capability of the BERT algorithm to extract sequence features from the semantic information of circRNA and miRNA. Then, a heterogeneous network is constructed based on cosine similarity and known CMI information. The Metapath2vec is employed to conduct random walks following meta-paths in the network to capture topological features, including similarity features. Finally, potential CMIs are predicted using the XGBoost classifier. BCMCMI achieves superior results compared to other state-of-the-art models on two benchmark datasets for CMI prediction. We also utilize t-SNE to visually observe the distribution of the extracted features on a randomly selected dataset. The remarkable prediction results show that BCMCMI can serve as a valuable complement to the wet experiment process.

KS-CMI: A circRNA-miRNA interaction prediction method based on the signed graph neural network and denoising autoencoder.

Circular RNA (circRNA) plays an important role in the diagnosis, treatment, and prognosis of human diseases. The discovery of potential circRNA-miRNA interactions (CMI) is of guiding significance for subsequent biological experiments. Limited by the small amount of experimentally supported data and high randomness, existing models are difficult to accomplish the CMI prediction task based on real cases. In this paper, we propose KS-CMI, a novel method for effectively accomplishing CMI prediction in real cases. KS-CMI enriches the 'behavior relationships' of molecules by constructing circRNA-miRNA-cancer (CMCI) networks and extracts the behavior relationship attribute of molecules based on balance theory. Next, the denoising autoencoder (DAE) is used to enhance the feature representation of molecules. Finally, the CatBoost classifier was used for prediction. KS-CMI achieved the most reliable prediction results in real cases and achieved competitive performance in all datasets in the CMI prediction.

A feature extraction method based on noise reduction for circRNA-miRNA interaction prediction combining multi-structure features in the association networks.

MOTIVATION: A large number of studies have shown that circular RNA (circRNA) affects biological processes by competitively binding miRNA, providing a new perspective for the diagnosis, and treatment of human diseases. Therefore, exploring the potential circRNA-miRNA interactions (CMIs) is an important and urgent task at present. Although some computational methods have been tried, their performance is limited by the incompleteness of feature extraction in sparse networks and the low computational efficiency of lengthy data. RESULTS: In this paper, we proposed JSNDCMI, which combines the multi-structure feature extraction framework and Denoising Autoencoder (DAE) to meet the challenge of CMI prediction in sparse networks. In detail, JSNDCMI integrates functional similarity and local topological structure similarity in the CMI network through the multi-structure feature extraction framework, then forces the neural network to learn the robust representation of features through DAE and finally uses the Gradient Boosting Decision Tree classifier to predict the potential CMIs. JSNDCMI produces the best performance in the 5-fold cross-validation of all data sets. In the case study, seven of the top 10 CMIs with the highest score were verified in PubMed. AVAILABILITY: The data and source code can be found at https://github.com/1axin/JSNDCMI.

LPIH2V: LncRNA-protein interactions prediction using HIN2Vec based on heterogeneous networks model.

LncRNA-protein interaction plays an important role in the development and treatment of many human diseases. As the experimental approaches to determine lncRNA-protein interactions are expensive and time-consuming, considering that there are few calculation methods, therefore, it is urgent to develop efficient and accurate methods to predict lncRNA-protein interactions. In this work, a model for heterogeneous network embedding based on meta-path, namely LPIH2V, is proposed. The heterogeneous network is composed of lncRNA similarity networks, protein similarity networks, and known lncRNA-protein interaction networks. The behavioral features are extracted in a heterogeneous network using the HIN2Vec method of network embedding. The results showed that LPIH2V obtains an AUC of 0.97 and ACC of 0.95 in the 5-fold cross-validation test. The model successfully showed superiority and good generalization ability. Compared to other models, LPIH2V not only extracts attribute characteristics by similarity, but also acquires behavior properties by meta-path wandering in heterogeneous networks. LPIH2V would be beneficial in forecasting interactions between lncRNA and protein.

DeepMPF: deep learning framework for predicting drug-target interactions based on multi-modal representation with meta-path semantic analysis.

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.

PPAEDTI: Personalized Propagation Auto-Encoder Model for Predicting Drug-Target Interactions.

Identifying protein targets for drugs establishes an indispensable knowledge foundation for drug repurposing and drug development. Though expensive and time-consuming, vitro trials are widely employed to discover drug targets, and the existing relevant computational algorithms still cannot satisfy the demand for real application in drug R&D with regards to the prediction accuracy and performance efficiency, which are urgently needed to be improved. To this end, we propose here the PPAEDTI model, which uses the graph personalized propagation technique to predict drug-target interactions from the known interaction network. To evaluate the prediction performance, six benchmark datasets were used for testing with some state-of-the-art methods compared. As a result, using the 5-fold cross-validation, the proposed PPAEDTI model achieves average AUCs>90% on 5 collected datasets. We also manually checked the top-20 prediction list for 2 proteins (hsa:775 and hsa:779) and a kind of drug (D00618), and successfully confirmed 18, 17, and 20 items from the public datasets, respectively. The experimental results indicate that, given known drug-target interactions, the PPAEDTI model can provide accurate predictions for the new ones, which is anticipated to serve as a useful tool for pharmacology research. Using the proposed model that was trained with the collected datasets, we have built a computational platform that is accessible at http://120.77.11.78/PPAEDTI/ and corresponding codes and datasets are also released.

KGDCMI: A New Approach for Predicting circRNA-miRNA Interactions From Multi-Source Information Extraction and Deep Learning.

Emerging evidence has revealed that circular RNA (circRNA) is widely distributed in mammalian cells and functions as microRNA (miRNA) sponges involved in transcriptional and posttranscriptional regulation of gene expression. Recognizing the circRNA-miRNA interaction provides a new perspective for the detection and treatment of human complex diseases. Compared with the traditional biological experimental methods used to predict the association of molecules, which are limited to the small-scale and are time-consuming and laborious, computing models can provide a basis for biological experiments at low cost. Considering that the proposed calculation model is limited, it is necessary to develop an effective computational method to predict the circRNA-miRNA interaction. This study thus proposed a novel computing method, named KGDCMI, to predict the interactions between circRNA and miRNA based on multi-source information extraction and fusion. The KGDCMI obtains RNA attribute information from sequence and similarity, capturing the behavior information in RNA association through a graph-embedding algorithm. Then, the obtained feature vector is extracted further by principal component analysis and sent to the deep neural network for information fusion and prediction. At last, KGDCMI obtains the prediction accuracy (area under the curve [AUC] = 89.30% and area under the precision-recall curve [AUPR] = 87.67%). Meanwhile, with the same dataset, KGDCMI is 2.37% and 3.08%, respectively, higher than the only existing model, and we conducted three groups of comparative experiments, obtaining the best classification strategy, feature extraction parameters, and dimensions. In addition, in the performed case study, 7 of the top 10 interaction pairs were confirmed in PubMed. These results suggest that KGDCMI is a feasible and useful method to predict the circRNA-miRNA interaction and can act as a reliable candidate for related RNA biological experiments.

A biomedical knowledge graph-based method for drug-drug interactions prediction through combining local and global features with deep neural networks.

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/.

A novel circRNA-miRNA association prediction model based on structural deep neural network embedding.

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.

SGCNCMI: A New Model Combining Multi-Modal Information to Predict circRNA-Related miRNAs, Diseases and Genes.

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.

BNEMDI: A Novel MicroRNA-Drug Interaction Prediction Model Based on Multi-Source Information With a Large-Scale Biological Network.

As a novel target in pharmacy, microRNA (miRNA) can regulate gene expression under specific disease conditions to produce specific proteins. To date, many researchers leveraged miRNA to reveal drug efficacy and pathogenesis at the molecular level. As we all know that conventional wet experiments suffer from many problems, including time-consuming, labor-intensity, and high cost. Thus, there is an urgent need to develop a novel computational model to facilitate the identification of miRNA-drug interactions (MDIs). In this work, we propose a novel bipartite network embedding-based method called BNEMDI to predict MDIs. First, the Bipartite Network Embedding (BiNE) algorithm is employed to learn the topological features from the network. Then, the inherent attributes of drugs and miRNAs are expressed as attribute features by MACCS fingerprints and k-mers. Finally, we feed these features into deep neural network (DNN) for training the prediction model. To validate the prediction ability of the BNEMDI model, we apply it to five different benchmark datasets under five-fold cross-validation, and the proposed model obtained excellent AUC values of 0.9568, 0.9420, 0.8489, 0.8774, and 0.9005 in ncDR, RNAInter, SM2miR1, SM2miR2, and SM2miR MDI datasets, respectively. To further verify the prediction performance of the BNEMDI model, we compare it with some existing powerful methods. We also compare the BiNE algorithm with several different network embedding methods. Furthermore, we carry out a case study on a common drug named 5-fluorouracil. Among the top 50 miRNAs predicted by the proposed model, there were 38 verified by the experimental literature. The comprehensive experiment results demonstrated that our method is effective and robust for predicting MDIs. In the future work, we hope that the BNEMDI model can be a reliable supplement method for the development of pharmacology and miRNA therapeutics.

BioChemDDI: Predicting Drug-Drug Interactions by Fusing Biochemical and Structural Information through a Self-Attention Mechanism.

During the development of drug and clinical applications, due to the co-administration of different drugs that have a high risk of interfering with each other's mechanisms of action, correctly identifying potential drug-drug interactions (DDIs) is important to avoid a reduction in drug therapeutic activities and serious injuries to the organism. Therefore, to explore potential DDIs, we develop a computational method of integrating multi-level information. Firstly, the information of chemical sequence is fully captured by the Natural Language Processing (NLP) algorithm, and multiple biological function similarity information is fused by Similarity Network Fusion (SNF). Secondly, we extract deep network structure information through Hierarchical Representation Learning for Networks (HARP). Then, a highly representative comprehensive feature descriptor is constructed through the self-attention module that efficiently integrates biochemical and network features. Finally, a deep neural network (DNN) is employed to generate the prediction results. Contrasted with the previous supervision model, BioChemDDI innovatively introduced graph collapse for extracting a network structure and utilized the biochemical information during the pre-training process. The prediction results of the benchmark dataset indicate that BioChemDDI outperforms other existing models. Moreover, the case studies related to three cancer diseases, including breast cancer, hepatocellular carcinoma and malignancies, were analyzed using BioChemDDI. As a result, 24, 18 and 20 out of the top 30 predicted cancer-related drugs were confirmed by the databases. These experimental results demonstrate that BioChemDDI is a useful model to predict DDIs and can provide reliable candidates for biological experiments. The web server of BioChemDDI predictor is freely available to conduct further studies.