CircRNAs are a particular single-stranded, circular structure and “non-coding” RNA molecules, with various biological functions . Existing studies have demonstrated the fundamental role of circRNAs in gene expression regulation and their significant involvement in the development of diverse complex diseases. Predicting the protein binding sites in circRNA can aid in comprehending the regulation mechanism involved in circRNA-protein binding during gene expression and facilitate the investigation of potential diagnosis and treatment strategies for complex diseases. This review begins by introducing the concept and functions of circRNAs, as well as their involvement in gene expression regulation . Then, some critical and publicly accessible databases about circRNA annotation, protein annotation, circRNA-protein binding were listed. Next, we present a brief introduction to the computational model for predicting circRNA-protein binding, followed by model performance comparison and suggestions for non-computer science experts on model selection. Finally, we examine the problems, limitations, and advantages of computational models and explore the further direction of circRNA-protein prediction, such as developing new and complex computational models, introducing complex biological sequence encoding schemes, and integrating additional biological data related to circRNA-protein binding.

The gene regulatory network (GRN) plays a vital role in understanding the structure and dynamics of cellular systems, revealing complex regulatory relationships, and exploring disease mechanisms. Recently, deep learning (DL)-based methods have been proposed to infer GRNs from single-cell transcriptomic data and achieved impressive performance. However, these methods do not fully utilize graph topological information and high-order neighbor information from multiple receptive fields. To overcome those limitations, we propose a novel model based on multiview graph attention network, namely, scMGATGRN, to infer GRNs. scMGATGRN mainly consists of GAT, multiview, and view-level attention mechanism. GAT can extract essential features of the gene regulatory network. The multiview model can simultaneously utilize local feature information and high-order neighbor feature information of nodes in the gene regulatory network. The view-level attention mechanism dynamically adjusts the relative importance of node embedding representations and efficiently aggregates node embedding representations from two views. To verify the effectiveness of scMGATGRN, we compared its performance with 10 methods (five shallow learning algorithms and five state-of-the-art DL-based methods) on seven benchmark single-cell RNA sequencing (scRNA-seq) datasets from five cell lines (two in human and three in mouse) with four different kinds of ground-truth networks. The experimental results not only show that scMGATGRN outperforms competing methods but also demonstrate the potential of this model in inferring GRNs. The code and data of scMGATGRN are made freely available on GitHub (https://github.com/nathanyl/scMGATGRN).

Circular RNAs (circRNAs) play vital roles in transcription and translation. Identification of circRNA-RBP (RNA-binding protein) interaction sites has become a fundamental step in molecular and cell biology. Deep learning (DL)-based methods have been proposed to predict circRNA-RBP interaction sites and achieved impressive identification performance. However, those methods cannot effectively capture long-distance dependencies, and cannot effectively utilize the interaction information of multiple features. To overcome those limitations, we propose a DL-based model iCRBP-LKHA using deep hybrid networks for identifying circRNA-RBP interaction sites. iCRBP-LKHA adopts five encoding schemes. Meanwhile, the neural network architecture, which consists of large kernel convolutional neural network (LKCNN), convolutional block attention module with one-dimensional convolution (CBAM-1D) and bidirectional gating recurrent unit (BiGRU), can explore local information, global context information and multiple features interaction information automatically. To verify the effectiveness of iCRBP-LKHA, we compared its performance with shallow learning algorithms on 37 circRNAs datasets and 37 circRNAs stringent datasets. And we compared its performance with state-of-the-art DL-based methods on 37 circRNAs datasets, 37 circRNAs stringent datasets and 31 linear RNAs datasets. The experimental results not only show that iCRBP-LKHA outperforms other competing methods, but also demonstrate the potential of this model in identifying other RNA-RBP interaction sites.

Accumulating evidence suggests that circRNAs play crucial roles in human diseases. CircRNA-disease association prediction is extremely helpful in understanding pathogenesis, diagnosis, and prevention, as well as identifying relevant biomarkers. During the past few years, a large number of deep learning (DL) based methods have been proposed for predicting circRNA-disease association and achieved impressive prediction performance. However, there are two main drawbacks to these methods. The first is these methods underutilize biometric information in the data. Second, the features extracted by these methods are not outstanding to represent association characteristics between circRNAs and diseases. In this study, we developed a novel deep learning model, named iCircDA-NEAE, to predict circRNA-disease associations. In particular, we use disease semantic similarity, Gaussian interaction profile kernel, circRNA expression profile similarity, and Jaccard similarity simultaneously for the first time, and extract hidden features based on accelerated attribute network embedding (AANE) and dynamic convolutional autoencoder (DCAE). Experimental results on the circR2Disease dataset show that iCircDA-NEAE outperforms other competing methods significantly. Besides, 16 of the top 20 circRNA-disease pairs with the highest prediction scores were validated by relevant literature. Furthermore, we observe that iCircDA-NEAE can effectively predict new potential circRNA-disease associations.

Attention mechanism has the ability to find important information in the sequence. The regions of the RNA sequence that can bind to proteins are more important than those that cannot bind to proteins. Neither conventional methods nor deep learning-based methods, they are not good at learning this information. In this study, LSTM is used to extract the correlation features between different sites in RNA sequence. We also use attention mechanism to evaluate the importance of different sites in RNA sequence. We get the optimal combination of k-mer length, k-mer stride window, k-mer sentence length, k-mer sentence stride window, and optimization function through hyper-parm experiments. The results show that the performance of our method is better than other methods. We tested the effects of changes in k-mer vector length on model performance. We show model performance changes under various k-mer related parameter settings. Furthermore, we investigate the effect of attention mechanism and RNA structure data on model performance.

DNA/RNA motif mining is the foundation of gene function research. The DNA/RNA motif mining plays an extremely important role in identifying the DNA- or RNA-protein binding site, which helps to understand the mechanism of gene regulation and management. For the past few decades, researchers have been working on designing new efficient and accurate algorithms for mining motif. These algorithms can be roughly divided into two categories: the enumeration approach and the probabilistic method. In recent years, machine learning methods had made great progress, especially the algorithm represented by deep learning had achieved good performance. Existing deep learning methods in motif mining can be roughly divided into three types of models: convolutional neural network (CNN) based models, recurrent neural network (RNN) based models, and hybrid CNN-RNN based models. We introduce the application of deep learning in the field of motif mining in terms of data preprocessing, features of existing deep learning architectures and comparing the differences between the basic deep learning models. Through the analysis and comparison of existing deep learning methods, we found that the more complex models tend to perform better than simple ones when data are sufficient, and the current methods are relatively simple compared with other fields such as computer vision, language processing (NLP), computer games, etc. Therefore, it is necessary to conduct a summary in motif mining by deep learning, which can help researchers understand this field.

BACKGROUND: LncRNAs (Long non-coding RNAs) are a type of non-coding RNA molecule with transcript length longer than 200 nucleotides. LncRNA has been novel candidate biomarkers in cancer diagnosis and prognosis. However, it is difficult to discover the true association mechanism between lncRNAs and complex diseases. The unprecedented enrichment of multi-omics data and the rapid development of machine learning technology provide us with the opportunity to design a machine learning framework to study the relationship between lncRNAs and complex diseases. RESULTS: In this article, we proposed a new machine learning approach, namely LGDLDA (LncRNA-Gene-Disease association networks based LncRNA-Disease Association prediction), for disease-related lncRNAs association prediction based multi-omics data, machine learning methods and neural network neighborhood information aggregation. Firstly, LGDLDA calculates the similarity matrix of lncRNA, gene and disease respectively, and it calculates the similarity between lncRNAs through the lncRNA expression profile matrix, lncRNA-miRNA interaction matrix and lncRNA-protein interaction matrix. We obtain gene similarity matrix by calculating the lncRNA-gene association matrix and the gene-disease association matrix, and we obtain disease similarity matrix by calculating the disease ontology, the disease-miRNA association matrix, and Gaussian interaction profile kernel similarity. Secondly, LGDLDA integrates the neighborhood information in similarity matrices by using nonlinear feature learning of neural network. Thirdly, LGDLDA uses embedded node representations to approximate the observed matrices. Finally, LGDLDA ranks candidate lncRNA-disease pairs and then selects potential disease-related lncRNAs. CONCLUSIONS: Compared with lncRNA-disease prediction methods, our proposed method takes into account more critical information and obtains the performance improvement cancer-related lncRNA predictions. Randomly split data experiment results show that the stability of LGDLDA is better than IDHI-MIRW, NCPLDA, LncDisAP and NCPHLDA. The results on different simulation data sets show that LGDLDA can accurately and effectively predict the disease-related lncRNAs. Furthermore, we applied the method to three real cancer data including gastric cancer, colorectal cancer and breast cancer to predict potential cancer-related lncRNAs.

Discovery of transcription factor binding sites (TFBSs) is essential for understanding the underlying binding mechanisms and cellular functions. Recently, Convolutional neural network (CNN) has succeeded in predicting TFBSs from the primary DNA sequences. In addition to DNA sequences, several evidences suggest that protein-DNA binding is partly mediated by properties of DNA shape. Although many methods have been proposed to jointly account for DNA sequences and shape properties in predicting TFBSs, they ignore the power of the combination of deep learning and DNA sequence + shape. Therefore we develop a deep-learning-based sequence + shape framework (DLBSS) in this paper, which appropriately integrates DNA sequences and shape properties, to better understand protein-DNA binding preference. This method uses a shared CNN to find their common patterns from DNA sequences and their corresponding shape features, which are then concatenated to compute a predicted value. Using 66 in-vitro datasets derived from universal protein binding microarrays (uPBMs), we show that our proposed method DLBSS significantly improves the performance of predicting TFBSs. In addition, we explain the reason why we should use the shared CNN, and explore the performance of DLBSS when using a deeper CNN, through a series of experiments.

RNA-Protein binding is involved in many different biological processes. With the progress of technology, more and more data are available for research. Based on these data, many prediction methods have been proposed to predict RNA-Protein binding preference. Some of these methods use only RNA sequence features for prediction, and some methods use multiple features for prediction. But, the performance of these methods is not satisfactory. In this study, we propose an improved capsule network to predict RNA-protein binding preferences, which can use both RNA sequence features and structure features. Experimental results show that our proposed method iCapsule performs better than three baseline methods in this field. We used both RNA sequence features and structure features in the model, so we tested the effect of primary capsule layer changes on model performance. In addition, we also studied the impact of model structure on model performance by performing our proposed method with different number of convolution layers and different kernel sizes.

RNA-Protein binding plays important roles in the field of gene expression. With the development of high throughput sequencing, several conventional methods and deep learning-based methods have been proposed to predict the binding preference of RNA-protein binding. These methods can hardly meet the need of consideration of the dependencies between subsequence and the various motif lengths of different translation factors (TFs). To overcome such limitations, we propose a predictive model that utilizes a combination of multi-scale convolutional layers and bidirectional gated recurrent unit (GRU) layer. Multi-scale convolution layer has the ability to capture the motif features of different lengths, and bidirectional GRU layer is able to capture the dependencies among subsequence. Experimental results show that the proposed method performs better than four state-of-the-art methods in this field. In addition, we investigate the effect of model structure on model performance by performing our proposed method with a different convolution layer and a different number of kernel size. We also demonstrate the effectiveness of bidirectional GRU in improving model performance through comparative experiments.