Aggregating evidences have shown that long non-coding RNAs (lncRNAs) generally play key roles in cellular biological processes such as epigenetic regulation, gene expression regulation at transcriptional and post-transcriptional levels, cell differentiation, and others. However, most lncRNAs have not been functionally characterized. There is an urgent need to develop computational approaches for function annotation of increasing available lncRNAs. In this article, we propose a global network-based method, KATZLGO, to predict the functions of human lncRNAs at large scale. A global network is constructed by integrating three heterogeneous networks: lncRNA-lncRNA similarity network, lncRNA-protein association network, and protein-protein interaction network. The KATZ measure is then employed to calculate similarities between lncRNAs and proteins in the global network. We annotate lncRNAs with Gene Ontology (GO) terms of their neighboring protein-coding genes based on the KATZ similarity scores. The performance of KATZLGO is evaluated on a manually annotated lncRNA benchmark and a protein-coding gene benchmark with known function annotations. KATZLGO significantly outperforms state-of-the-art computational method both in maximum F-measure and coverage. Furthermore, we apply KATZLGO to predict functions of human lncRNAs and successfully map 12,318 human lncRNA genes to GO terms.

MicroRNAs (miRNAs) have been demonstrated to play significant biological roles in many human biological processes. Inferring the functions of miRNAs is an important strategy for understanding disease pathogenesis at the molecular level. In this paper, we propose an integrated model, PmiRGO, to infer the gene ontology (GO) functions of miRNAs by integrating multiple data sources, including the expression profiles of miRNAs, miRNA-target interactions, and protein-protein interactions (PPI). PmiRGO starts by building a global network consisting of three networks. Then, it employs DeepWalk to learn latent representations as network features of the global heterogeneous network. Finally, the SVM-based models are applied to label the GO terms of miRNAs. The experimental results show that PmiRGO has a significantly better performance than existing state-of-the-art methods in terms of F_max. A case study further demonstrates the feasibility of PmiRGO to annotate the potential functions of miRNAs.

Accumulating evidence has demonstrated dysfunctions of long non-coding RNAs (lncRNAs) are involved in various complex human diseases. However, even today, the relationships between lncRNAs and diseases remain unknown in most cases. Developing effective computational approaches to identify potential lncRNA-disease associations has become a hot topic. Existing network-based approaches are usually focused on the intrinsic features of lncRNAs and diseases but ignore the heterogeneous information of biological networks. Considering the limitations in previous methods, we propose LDAH2V, an efficient computational framework for predicting potential lncRNA-disease associations. LDAH2V uses the HIN2Vec to calculate the meta-path and feature vector for each lncRNA-disease pair in the heterogeneous information network (HIN), which consists of lncRNA similarity network, disease similarity network, miRNA similarity network, and the associations between them. Then, a Gradient Boosting Tree (GBT) classifier to predict lncRNA-disease associations is built with the feature vectors. The results show that LDAH2V performs significantly better than the four existing state-of-the-art methods and gains an AUC of 0.97 in the 10-fold cross-validation test. Furthermore, case studies of colon cancer and ovarian cancer-related lncRNAs have been confirmed in related databases and medical literature.

Hot spot residues at protein–RNA complexes are vitally important for investigating the underlying molecular recognition mechanism. Accurately identifying protein–RNA binding hot spots is critical for drug designing and protein engineering. Although some progress has been made by utilizing various available features and a series of machine learning approaches, these methods are still in the infant stage. In this paper, we present a new computational method named XGBPRH, which is based on an eXtreme Gradient Boosting (XGBoost) algorithm and can effectively predict hot spot residues in protein–RNA interfaces utilizing an optimal set of properties. Firstly, we download 47 protein–RNA complexes and calculate a total of 156 sequence, structure, exposure, and network features. Next, we adopt a two-step feature selection algorithm to extract a combination of 6 optimal features from the combination of these 156 features. Compared with the state-of-the-art approaches, XGBPRH achieves better performances with an area under the ROC curve (AUC) score of 0.817 and an F1-score of 0.802 on the independent test set. Meanwhile, we also apply XGBPRH to two case studies. The results demonstrate that the method can effectively identify novel energy hotspots.

With the development of sequencing technology, more and more long non-coding RNAs (lncRNAs) have been identified. Some lncRNAs have been confirmed that they play an important role in the process of development through the dosage compensation effect, epigenetic regulation, cell differentiation regulation and other aspects. However, the majority of the lncRNAs have not been functionally characterized. Explore the function of lncRNAs and the regulatory network has become a hot research topic currently. In the work, a network-based model named BiRWLGO is developed. The ultimate goal is to predict the probable functions for lncRNAs at large scale. The new model starts with building a global network composed of three networks: lncRNA similarity network, lncRNA-protein association network and protein-protein interaction (PPI) network. After that, it utilizes bi-random walk algorithm to explore the similarities between lncRNAs and proteins. Finally, we can annotate an lncRNA with the Gene Ontology (GO) terms according to its neighboring proteins. We compare the performance of BiRWLGO with the state-of-the-art models on a manually annotated lncRNA benchmark with known GO terms. The experimental results assert that BiRWLGO outperforms other methods in terms of both maximum F-measure (Fmax) and coverage. BiRWLGO is a relatively efficient method to predict the functions of lncRNA. When protein interaction data is integrated, the predictive performance of BiRWLGO gains a great improvement.

MicroRNAs (miRNAs) are a highly abundant collection of functional non-coding RNAs involved in cellular regulation and various complex human diseases. Although a large number of miRNAs have been identified, most of their physiological functions remain unknown. Computational methods play a vital role in exploring the potential functions of miRNAs. Here, we present DeepMiR2GO, a tool for integrating miRNAs, proteins and diseases, to predict the gene ontology (GO) functions based on multiple deep neuro-symbolic models. DeepMiR2GO starts by integrating the miRNA co-expression network, protein-protein interaction (PPI) network, disease phenotype similarity network, and interactions or associations among them into a global heterogeneous network. Then, it employs an efficient graph embedding strategy to learn potential network representations of the global heterogeneous network as the topological features. Finally, a deep multi-label classification network based on multiple neuro-symbolic models is built and used to annotate the GO terms of miRNAs. The predicted results demonstrate that DeepMiR2GO performs significantly better than other state-of-the-art approaches in terms of precision, recall, and maximum F-measure.