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.

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.

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.

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.