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.

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.

Accumulating evidences show that circular RNAs (circRNAs) play an important role in regulating gene expression, and involve in many complex human diseases. Identifying associations of circRNA with disease helps to understand the pathogenesis, treatment and diagnosis of complex diseases. Since inferring circRNA-disease associations by biological experiments is costly and time-consuming, there is an urgently need to develop a computational model to identify the association between them. In this paper, we proposed a novel method named KNN-NMF, which combines K nearest neighbors with nonnegative matrix factorization to infer associations between circRNA and disease (KNN-NMF). Frist, we compute the Gaussian Interaction Profile (GIP) kernel similarity of circRNA and disease, the semantic similarity of disease, respectively. Then, the circRNA-disease new interaction profiles are established using weight K nearest neighbors to reduce the false negative association impact on prediction performance. Finally, Nonnegative Matrix Factorization is implemented to predict associations of circRNA with disease. The experiment results indicate that the prediction performance of KNN-NMF outperforms the competing methods under five-fold cross-validation. Moreover, case studies of two common diseases further show that KNN-NMF can identify potential circRNA-disease associations effectively.

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/.

BACKGROUND: Self-interacting proteins (SIPs), two or more copies of the protein that can interact with each other expressed by one gene, play a central role in the regulation of most living cells and cellular functions. Although numerous SIPs data can be provided by using high-throughput experimental techniques, there are still several shortcomings such as in time-consuming, costly, inefficient, and inherently high in false-positive rates, for the experimental identification of SIPs even nowadays. Therefore, it is more and more significant how to develop efficient and accurate automatic approaches as a supplement of experimental methods for assisting and accelerating the study of predicting SIPs from protein sequence information. RESULTS: In this paper, we present a novel framework, termed GLCM-WSRC (gray level co-occurrence matrix-weighted sparse representation based classification), for predicting SIPs automatically based on protein evolutionary information from protein primary sequences. More specifically, we firstly convert the protein sequence into Position Specific Scoring Matrix (PSSM) containing protein sequence evolutionary information, exploiting the Position Specific Iterated BLAST (PSI-BLAST) tool. Secondly, using an efficient feature extraction approach, i.e., GLCM, we extract abstract salient and invariant feature vectors from the PSSM, and then perform a pre-processing operation, the adaptive synthetic (ADASYN) technique, to balance the SIPs dataset to generate new feature vectors for classification. Finally, we employ an efficient and reliable WSRC model to identify SIPs according to the known information of self-interacting and non-interacting proteins. CONCLUSIONS: Extensive experimental results show that the proposed approach exhibits high prediction performance with 98.10% accuracy on the yeast dataset, and 91.51% accuracy on the human dataset, which further reveals that the proposed model could be a useful tool for large-scale self-interacting protein prediction and other bioinformatics tasks detection in the future.

Identification of drug–target interactions (DTIs) is critical for discovering potential target protein candidates for new drugs. However, traditional experimental methods have limitations in discovering DTIs. They are time-consuming, tedious, and expensive, and often suffer from high false-positive rates and false-negative rates. Therefore, using computational methods to predict DTIs has received extensive attention from many researchers in recent years. To address this issue, in this paper, an effective prediction model is presented which is based on the information of drug molecular structure data and protein sequence data. It performs prediction with the following procedures. First, we transform the sequences of each target into a position-specific scoring matrix (PSSM), such that the features can retain biological evolutionary information. We then use a feature vector of molecular substructure fingerprints to describe the chemical structure information of the drug compounds. Second, the Legendre moments algorithm is used to extract new features from the PSSM. Finally, a classification algorithm called rotation forest is used to perform prediction, we tested its prediction performance on four golden standard data sets: enzymes, G-protein-coupled receptors, ion channels, and nuclear receptors. As a result, the proposed method achieves average accuracies of 0.9026, 0.8260, 0.8703, and 0.7444 on these four data sets using five-fold cross-validation. We also compare the proposed method with the support vector machine and other existing approaches. The proposed model is proved to be superior to comparative methods, showing that it is feasible, effective, and robust for predicting potential DTI.

Circular RNA (circRNA) is a kind of novel discovered non-coding RNA molecule with a closed loop structure, which plays a critical regulatory role in human diseases. Identifying the association between circRNAs and diseases has important potential value for the diagnosis and treatment of complex human diseases. Although biological experiments can more accurately identify the association between circRNAs and diseases, they are usually blind and limited by small scale and high cost. Therefore, there is an urgent need for efficient and feasible computational methods to predict the potential circRNA-disease associations on a large scale, so as to provide the most promising candidate for biological experiments. In this paper, we propose a novel computational method based on the deep Generative Adversarial Network (GAN) algorithm combined with the multi-source similarity information to predict the circRNA-disease associations. Firstly, we fuse the multi-source information of disease semantic similarity, disease and circRNA Gaussian interaction profile kernel similarity, and then use GAN to extract the hidden features of fusion information objectively and effectively in the way of confrontation learning, and finally send them to Logistic Model Tree (LMT) classifier for accurate prediction. The 5-fold cross-validation experiment of the proposed model achieved 89.2% accuracy with 89.4% precision at the AUC of 90.6% on the CIRCR2Disease dataset. Compared with the state-of-the-art SVM classifier and other feature extraction methods, the proposed model shows strong competitiveness. In addition, the predicted results of this model are supported by the biological experiments, and 9 of the top 15 circRNA-disease associations with the highest scores were confirmed by recently published literature. These promising results indicate that the proposed model is an effective tool for predicting circRNA-disease associations and can provide reliable candidates for biological experiments.

Emerging evidence has shown microRNAs (miRNAs) play an important role in human disease research. Identifying potential association among them is significant for the development of pathology, diagnose and therapy. However, only a tiny portion of all miRNA-disease pairs in the current datasets are experimentally validated. This prompts the development of high-precision computational methods to predict real interaction pairs. In this paper, we propose a new model of Logistic Model Tree for predicting miRNA-Disease Association (LMTRDA) by fusing multi-source information including miRNA sequences, miRNA functional similarity, disease semantic similarity, and known miRNA-disease associations. In particular, we introduce miRNA sequence information and extract its features using natural language processing technique for the first time in the miRNA-disease prediction model. In the cross-validation experiment, LMTRDA obtained 90.51% prediction accuracy with 92.55% sensitivity at the AUC of 90.54% on the HMDD V3.0 dataset. To further evaluate the performance of LMTRDA, we compared it with different classifier and feature descriptor models. In addition, we also validate the predictive ability of LMTRDA in human diseases including Breast Neoplasms, Breast Neoplasms and Lymphoma. As a result, 28, 27 and 26 out of the top 30 miRNAs associated with these diseases were verified by experiments in different kinds of case studies. These experimental results demonstrate that LMTRDA is a reliable model for predicting the association among miRNAs and diseases.

Protein-protein interactions (PPIs) perform a very important function in a number of cellular processes, including signal transduction, post-translational modifications, apoptosis, and cell growth. Deregulation of PPIs will lead to many diseases, including pernicious anemia or cancers. Although a large number of high-throughput techniques are designed to generate PPIs data, they are generally expensive, inefficient, and labor-intensive. Hence, there is an urgent need for developing a computational method to accurately and rapidly detect PPIs. In this article, we proposed a highly efficient method to detect PPIs by integrating a new protein sequence sub-stitution matrix feature representation and ensemble weighted sparse representation model classifier. The proposed method is demonstrated on Saccharomyces cerevisiae dataset and achieved 99.26 percent prediction accuracy with 98.53 percent sensitivity at precision of 100 percent, which is shown to have much higher predictive accuracy than the state-of-the-art methods. Extensive contrast experiments are performed with the benchmark data set from Human and Helicobacter pylori that our proposed method can achieve outstanding better success rates than other existing approaches in this problem. Experiment results illustrate that our proposed method presents an economical approach for computational building of PPI networks, which can be a helpful supplementary method for future proteomics researches.