circRNA-disease Associations Research Articles

SGFCCDA: Scale Graph Convolutional Networks and Feature Convolution for circRNA-Disease Association Prediction.

Circular RNAs (circRNAs) have emerged as a novel class of non-coding RNAs with regulatory roles in disease pathogenesis. Computational models aimed at predicting circRNA-disease associations offer valuable insights into disease mechanisms, thereby enabling the development of innovative diagnostic and therapeutic approaches while reducing the reliance on costly wet experiments. In this study, SGFCCDA is proposed for predicting potential circRNA-disease associations based on scale graph convolutional networks and feature convolution. Specifically, SGFCCDA integrates multiple measures of circRNA and disease similarity and combines known association information to construct a heterogeneous network. This network is then explored by scale graph convolutional networks to capture both topological and attribute information. Additionally, convolutional neural networks are employed to further learn the features and obtain higher-order feature representations containing richer information about nodes. The Hadamard product is utilized to effectively combine circRNA features with disease features, and a multilayer perceptron is applied to predict the association between each pair of circRNA and disease. Five-fold cross validation experiments conducted on the CircR2Disease dataset demonstrate the accurate prediction capabilities of SGFCCDA in identifying potential circRNA-disease associations. Furthermore, case studies provide further confirmation of SGFCCDA's ability to identify disease-associated circRNAs.

Predicting circRNA-Disease Associations by Using Multi-Biomolecular Networks Based on Variational Graph Auto-Encoder with Attention Mechanism

Predicting circRNA-Disease Associations by Using Multi-Biomolecular Networks Based on Variational Graph Auto-Encoder with Attention Mechanism

LGCDA: Predicting CircRNA-Disease Association Based on Fusion of Local and Global Features.

CircRNA has been shown to be involved in the occurrence of many diseases. Several computational frameworks have been proposed to identify circRNA-disease associations. Despite the existing computational methods have obtained considerable successes, these methods still require to be improved as their performance may degrade due to the sparsity of the data and the problem of memory overflow. We develop a novel computational framework called LGCDA to predict circRNA-disease associations by fusing local and global features to solve the above mentioned problems. First, we construct closed local subgraphs by using k-hop closed subgraph and label the subgraphs to obtain rich graph pattern information. Then, the local features are extracted by using graph neural network (GNN). In addition, we fuse Gaussian interaction profile (GIP) kernel and cosine similarity to obtain global features. Finally, the score of circRNA-disease associations is predicted by using the multilayer perceptron (MLP) based on local and global features. We perform five-fold cross validation on five datasets for model evaluation and our model surpasses other advanced methods.

RDGAN: Prediction of circRNA-Disease Associations via Resistance Distance and Graph Attention Network.

As a series of single-stranded RNAs, circRNAs have been implicated in numerous diseases and can serve as valuable biomarkers for disease therapy and prevention. However, traditional biological experiments demand significant time and effort. Therefore, various computational methods have been proposed to address this limitation, but how to extract features more comprehensively remains a challenge that needs further attention in the future. In this study, we propose a unique approach to predict circRNA-disease associations based on resistance distance and graph attention network (RDGAN). First, the associations of circRNA and disease are obtained by fusing multiple databases, and resistance distance as a similarity matrix is used to further deal with the sparse of the similarity matrices. Then the circRNA-disease heterogeneous network is constructed based on the similiarity of circRNA-circRNA, disease-disease and the known circRNA-disease adjacency matric. Second, leveraging the three neural network modules-ResGatedGraphConv, GAT and MFConv-we gather node feature embeddings collected from the heterogeneous network. Subsequently, all the characteristics are supplied to the self-attention mechanism to predict new potential connections. Finally, our model obtains a remarkable AUC value of 0.9630 through five-fold cross-validation, surpassing the predictive performance of the other eight state-of-the-art models.

An ensemble approach for circular RNA-disease association prediction using variational autoencoder and genetic algorithm.

Circular RNAs (circRNAs) are endogenous non-coding RNAs with a covalently closed loop structure. They have many biological functions, mainly regulatory ones. They have been proven to modulate protein-coding genes in the human genome. CircRNAs are linked to various diseases like Alzheimer's disease, diabetes, atherosclerosis, Parkinson's disease and cancer. Identifying the associations between circular RNAs and diseases is essential for disease diagnosis, prevention, and treatment. The proposed model, based on the variational autoencoder and genetic algorithm circular RNA disease association (VAGA-CDA), predicts novel circRNA-disease associations. First, the experimentally verified circRNA-disease associations are augmented with the synthetic minority oversampling technique (SMOTE) and regenerated using a variational autoencoder, and feature selection is applied to these vectors by a genetic algorithm (GA). The variational autoencoder effectively extracts features from the augmented samples. The optimized feature selection of the genetic algorithm effectively carried out dimensionality reduction. The sophisticated feature vectors extracted are then given to a Random Forest classifier to predict new circRNA-disease associations. The proposed model yields an AUC value of 0.9644 and 0.9628 under 5-fold and 10-fold cross-validations, respectively. The results of the case studies indicate the robustness of the proposed model.

DETHACDA: A Dual-View Edge and Topology Hybrid Attention Model for CircRNA-Disease Associations Prediction.

There exists growing evidence that circRNAs are concerned with many complex diseases physiological processes and pathogenesis and may serve as critical therapeutic targets. Identifying disease-associated circRNAs through biological experiments is time-consuming, and designing an intelligent, precise calculation model is essential. Recently, many models based on graph technology have been proposed to predict circRNA-disease association. However, most existing methods only capture the neighborhood topology of the association network and ignore the complex semantic information. Therefore, we propose a Dual-view Edge and Topology Hybrid Attention model for predicting CircRNA-Disease Associations (DETHACDA), effectively capturing the neighborhood topology and various semantics of circRNA and disease nodes in a heterogeneous network. The 5-fold cross-validation experiments on circRNADisease indicate that the proposed DETHACDA achieves the area under receiver operating characteristic curve of 0.9882, better than four state-of-the-art calculation methods.

AMDECDA: Attention Mechanism Combined With Data Ensemble Strategy for Predicting CircRNA-Disease Association

AMDECDA: Attention Mechanism Combined With Data Ensemble Strategy for Predicting CircRNA-Disease Association

Identifying circRNA-disease association based on relational graph attention network and hypergraph attention network

In recent years, with the in-depth study of circRNA, scholars have begun to discover a synergistic relationship between circRNA and microorganisms. Traditional wet lab experiments in biology require expensive financial, material, and human resources to investigate the relationship between circRNA and diseases. Therefore, we propose a new predictive model for inferring the association between circRNA and diseases, called HAGACDA. Specifically, we first aggregate the unique features of circRNA and diseases themselves through singular value decomposition, Pearson similarity, and the biological information characteristics of circRNA and diseases. Utilizing the competitive relationships between miRNA and other microorganisms, we construct a circRNA-miRNA-disease multi-source heterogeneous network. Subsequently, we use a relational graph attention network to aggregate features based on the structural connections between different nodes. To address the inherent limitations in capturing high-order patterns in edge sets, we integrate a hypergraph attention network to extract features of circRNA and diseases. Finally, association prediction scores for node pairs are obtained through a multilayer perceptron. We conducted a comprehensive analysis of the model, including comparative experiments and case studies. Experimental results demonstrate that our model accurately predicts the association between circRNA and diseases.

MAMLCDA: A Meta-Learning Model for Predicting circRNA-Disease Association Based on MAML Combined With CNN.

Circular RNAs (circRNAs) exist in vivo and are a class of noncoding RNA molecules. They have a single-stranded, closed, annular structure. Many studies have shown that circRNAs and diseases are linked. Therefore, it is critical to build a reliable and accurate predictor to find the circRNA-disease association. In this paper, we presented a meta-learning model named MAMLCDA to identify the circRNA-disease association, which is based on model-agnostic meta-learning (MAML) combined with CNN classification. Specifically, similarities between diseases and circRNAs are extracted and integrated to characterize their relationships, and k-means is used to cluster majority samples and select a certain number of samples from each cluster to obtain the same number of negative samples as the positive samples. To further reduce the dimension of the features and save operation time, we applied probabilistic principal component analysis (PPCA) to compact the integrated circRNA and disease similarity network feature vectors. The feature vectors are converted into images. At this time, the prediction problem is transformed into the 2-way 1-shot problem of the image and input into the model with MAML as the meta-learner and CNN as the base-learner. Comparison results of five-fold cross-validation on two benchmark datasets illustrate that MAMLCDA outperforms several state-of-the-art approaches with the best accuracies of 95.33% and 98%. Therefore, MAMLCDA can help to understand the pathogenesis of complex diseases at the circRNA level.

Exploring potential circRNA biomarkers for cancers based on double-line heterogeneous graph representation learning

BackgroundCompared with the time-consuming and labor-intensive for biological validation in vitro or in vivo, the computational models can provide high-quality and purposeful candidates in an instant. Existing computational models face limitations in effectively utilizing sparse local structural information for accurate predictions in circRNA-disease associations. This study addresses this challenge with a proposed method, CDA-DGRL (Prediction of CircRNA-Disease Association based on Double-line Graph Representation Learning), which employs a deep learning framework leveraging graph networks and a dual-line representation model integrating graph node features.MethodCDA-DGRL comprises several key steps: initially, the integration of diverse biological information to compute integrated similarities among circRNAs and diseases, leading to the construction of a heterogeneous network specific to circRNA-disease associations. Subsequently, circRNA and disease node features are derived using sparse autoencoders. Thirdly, a graph convolutional neural network is employed to capture the local graph network structure by inputting the circRNA-disease heterogeneous network alongside node features. Fourthly, the utilization of node2vec facilitates depth-first sampling of the circRNA-disease heterogeneous network to grasp the global graph network structure, addressing issues associated with sparse raw data. Finally, the fusion of local and global graph network structures is inputted into an extra trees classifier to identify potential circRNA-disease associations.ResultsThe results, obtained through a rigorous five-fold cross-validation on the circR2Disease dataset, demonstrate the superiority of CDA-DGRL with an AUC value of 0.9866 and an AUPR value of 0.9897 compared to existing state-of-the-art models. Notably, the hyper-random tree classifier employed in this model outperforms other machine learning classifiers.ConclusionThus, CDA-DGRL stands as a promising methodology for reliably identifying circRNA-disease associations, offering potential avenues to alleviate the necessity for extensive traditional biological experiments. The source code and data for this study are available at https://github.com/zywait/CDA-DGRL.

KFDAE: CircRNA-Disease Associations Prediction Based on Kernel Fusion and Deep Auto-Encoder.

CircRNA has been proved to play an important role in the diseases diagnosis and treatment. Considering that the wet-lab is time-consuming and expensive, computational methods are viable alternative in these years. However, the number of circRNA-disease associations (CDAs) that can be verified is relatively few, and some methods do not take full advantage of dependencies between attributes. To solve these problems, this paper proposes a novel method based on Kernel Fusion and Deep Auto-encoder (KFDAE) to predict the potential associations between circRNAs and diseases. Firstly, KFDAE uses a non-linear method to fuse the circRNA similarity kernels and disease similarity kernels. Then the vectors are connected to make the positive and negative sample sets, and these data are send to deep auto-encoder to reduce dimension and extract features. Finally, three-layer deep feedforward neural network is used to learn features and gain the prediction score. The experimental results show that compared with existing methods, KFDAE achieves the best performance. In addition, the results of case studies prove the effectiveness and practical significance of KFDAE, which means KFDAE is able to capture more comprehensive information and generate credible candidate for subsequent wet-lab.

GEHGAN[formula omitted] CircRNA–disease association prediction via graph embedding and heterogeneous graph attention network

There is growing proof suggested that circRNAs play a crucial function in diverse important biological reactions related to human diseases. Within the area of biochemistry, a massive range of wet experiments have been carried out to find out the connections of circRNA–disease in recent years. Since wet experiments are expensive and laborious, nowadays, calculation-based solutions have increasingly attracted the attention of researchers. However, the performance of these methods is restricted due to the inability to balance the distribution among various types of nodes. To remedy the problem, we present a novel computational method called GEHGAN to forecast the new relationships in this research, leveraging graph embedding and heterogeneous graph attention networks. Firstly, we calculate circRNA sequences similarity, circRNA RBP similarity, disease semantic similarity and corresponding GIP kernel similarity to construct heterogeneous graph. Secondly, a graph embedding method using random walks with jump and stay strategies is applied to obtain the preliminary embeddings of circRNAs and diseases, greatly improving the performance of the model. Thirdly, a multi-head graph attention network is employed to further update the embeddings, followed by the employment of the MLP as a predictor. As a result, the five-fold cross-validation indicates that GEHGAN achieves an outstanding AUC score of 0.9829 and an AUPR value of 0.9815 on the CircR2Diseasev2.0 database, and case studies on osteosarcoma, gastric and colorectal neoplasms further confirm the model’s efficacy at identifying circRNA–disease correlations.

Identification of circRNA-disease associations via multi-model fusion and ensemble learning.

Circular RNA (circRNA) is a common non-coding RNA and plays an important role in the diagnosis and therapy of human diseases, circRNA-disease associations prediction based on computational methods can provide a new way for better clinical diagnosis. In this article, we proposed a novel method for circRNA-disease associations prediction based on ensemble learning, named ELCDA. First, the association heterogeneous network was constructed via collecting multiple information of circRNAs and diseases, and multiple similarity measures are adopted here, then, we use metapath, matrix factorization and GraphSAGE-based models to extract features of nodes from different views, the final comprehensive features of circRNAs and diseases via ensemble learning, finally, a soft voting ensemble strategy is used to integrate the predicted results of all classifier. The performance of ELCDA is evaluated by fivefold cross-validation and compare with other state-of-the-art methods, the experimental results show that ELCDA is outperformance than others. Furthermore, three common diseases are used as case studies, which also demonstrate that ELCDA is an effective method for predicting circRNA-disease associations.

Bi-SGTAR: A simple yet efficient model for circRNA-disease association prediction based on known association pair only

Identifying circRNA (circular RNA) associated with diseases holds promise as diagnostic and prognostic biomarkers, offering potential avenues for novel therapeutics. Several computational methods have been designed to predict circRNA-disease associations. Unfortunately, current computational models face issues stemming from the integration of data from multiple sources, leading to blind spots in data combination and increased model complexity. Thus, this article introduces a novel method named Bi-SGTAR (Bi-view Sparse Gating and True Association Regression). Notably, Bi-SGTAR demonstrates comparable performance to existing multi-source information fusion methods while utilizing only known circRNA-disease association pairs. In contrast to previous methods, the model divides the adjacency matrix into two views and employs an encoder with sparse gating to assess the reliability of all associations. Additionally, a supervised reconstructor is employed to define the true association probability, quantifying the truthfulness of all associations. The Encoding-Reconstruction-Regression (ERR) framework adeptly merges both reliable and truthful associations from both views. The experimental results unequivocally show that Bi-SGTAR surpasses state-of-the-art models across seven circRNA-disease datasets, one lncRNA-disease dataset, and one microbe-drug dataset, with fewer data needed.

GSLCDA: An Unsupervised Deep Graph Structure Learning Method for Predicting CircRNA-Disease Association.

Growing studies reveal that Circular RNAs (circRNAs) are broadly engaged in physiological processes of cell proliferation, differentiation, aging, apoptosis, and are closely associated with the pathogenesis of numerous diseases. Clarification of the correlation among diseases and circRNAs is of great clinical importance to provide new therapeutic strategies for complex diseases. However, previous circRNA-disease association prediction methods rely excessively on the graph network, and the model performance is dramatically reduced when noisy connections occur in the graph structure. To address this problem, this paper proposes an unsupervised deep graph structure learning method GSLCDA to predict potential CDAs. Concretely, we first integrate circRNA and disease multi-source data to constitute the CDA heterogeneous network. Then the network topology is learned using the graph structure, and the original graph is enhanced in an unsupervised manner by maximize the inter information of the learned and original graphs to uncover their essential features. Finally, graph space sensitive k-nearest neighbor (KNN) algorithm is employed to search for latent CDAs. In the benchmark dataset, GSLCDA obtained 92.67% accuracy with 0.9279 AUC. GSLCDA also exhibits exceptional performance on independent datasets. Furthermore, 14, 12 and 14 of the top 16 circRNAs with the most points GSLCDA prediction scores were confirmed in the relevant literature in the breast cancer, colorectal cancer and lung cancer case studies, respectively. Such results demonstrated that GSLCDA can validly reveal underlying CDA and offer new perspectives for the diagnosis and therapy of complex human diseases.

LMGATCDA: Graph Neural Network With Labeling Trick for Predicting circRNA-Disease Associations.

Previous studies have proven that circular RNAs (circRNAs) are inextricably connected to the etiology and pathophysiology of complicated diseases. Since conventional biological research are frequently small-scale, expensive, and time-consuming, it is essential to establish an efficient and reasonable computation-based method to identify disease-related circRNAs. In this article, we proposed a novel ensemble model for predicting probable circRNA-disease associations based on multi-source similarity information(LMGATCDA). In particular, LMGATCDA first incorporates information on circRNA functional similarity, disease semantic similarity, and the Gaussian interaction profile (GIP) kernel similarity as explicit features, along with node-labeling of the three-hop subgraphs extracted from each linked target node as graph structural features. After that, the fused features are used as input, and further implied features are extracted by graph sampling aggregation (GraphSAGE) and multi-hop attention graph neural network (MAGNA). Finally, the prediction scores are obtained through a fully connected layer. With five-fold cross-validation, LMGATCDA demonstrated excellent competitiveness against gold standard data, reaching 95.37% accuracy and 91.31% recall with an AUC of 94.25% on the circR2Disease benchmark dataset. Collectively, the noteworthy findings from these case studies support our conclusion that the LMGATCDA model can provide reliable circRNA-disease associations for clinical research while helping to mitigate experimental uncertainties in wet-lab investigations.

MAGCDA: A Multi-Hop Attention Graph Neural Networks Method for CircRNA-Disease Association Prediction.

With a growing body of evidence establishing circular RNAs (circRNAs) are widely exploited in eukaryotic cells and have a significant contribution in the occurrence and development of many complex human diseases. Disease-associated circRNAs can serve as clinical diagnostic biomarkers and therapeutic targets, providing novel ideas for biopharmaceutical research. However, available computation methods for predicting circRNA-disease associations (CDAs) do not sufficiently consider the contextual information of biological network nodes, making their performance limited. In this work, we propose a multi-hop attention graph neural network-based approach MAGCDA to infer potential CDAs. Specifically, we first construct a multi-source attribute heterogeneous network of circRNAs and diseases, then use a multi-hop strategy of graph nodes to deeply aggregate node context information through attention diffusion, thus enhancing topological structure information and mining data hidden features, and finally use random forest to accurately infer potential CDAs. In the four gold standard data sets, MAGCDA achieved prediction accuracy of 92.58%, 91.42%, 83.46% and 91.12%, respectively. MAGCDA has also presented prominent achievements in ablation experiments and in comparisons with other models. Additionally, 18 and 17 potential circRNAs in top 20 predicted scores for MAGCDA prediction scores were confirmed in case studies of the complex diseases breast cancer and Almozheimer's disease, respectively. These results suggest that MAGCDA can be a practical tool to explore potential disease-associated circRNAs and provide a theoretical basis for disease diagnosis and treatment.

CircRNA-disease association prediction with an improved unbalanced Bi-Random walk

Studies show that circular RNAs (circRNAs), a type of non-coding RNAs, play various roles in biological processes such as the formation and progression of many different diseases. For this reason, identifying potential circRNAs associated with diseases is vital for early diagnosis. Determining these relationships experimentally requires a long process and is also expensive. For this reason, computational models are being developed to determine the relationships between circRNA and diseases. In this study, we recommend a technique called Improved Unbalanced Bi-Random Walk (UBRW) to identify potential circRNAs associated with diseases. The commonly used 5-fold cross-validation (CV) technique and leave one-out cross-validation (LOOCV) technique were applied to verify the predictive ability of our technique. The area under curve (AUC) values calculated in 5-fold CV and LOOCV are 0.8910 and 0.9669, respectively. Case studies on the commonly occurring gastric cancer and breast cancer were conducted to further validate the predictive performance of our method. When the results were examined, it was seen that the prediction ability of the UBRW method was quite successful.

KGRACDA: A Model Based on Knowledge Graph from Recursion and Attention Aggregation for CircRNA-disease Association Prediction.

CircRNA is closely related to human disease, so it is important to predict circRNA-disease association (CDA). However, the traditional biological detection methods have high difficulty and low accuracy, and computational methods represented by deep learning ignore the ability of the model to explicitly extract local depth information of the CDA. We propose a model based on knowledge graph from recursion and attention aggregation for circRNA-disease association prediction (KGRACDA). This model combines explicit structural features and implicit embedding information of graphs, optimizing graph embedding vectors. First, we built large-scale, multi-source heterogeneous datasets and construct a knowledge graph of multiple RNAs and diseases. After that, we use a recursive method to build multi-hop subgraphs and optimize graph attention mechanism by gating mechanism, mining local depth information. At the same time, the model uses multi-head attention mechanism to balance global and local depth features of graphs, and generate CDA prediction scores. KGRACDA surpasses other methods by capturing local and global depth information related to CDA. We update an interactive web platform HNRBase v2.0, which visualizes circRNA data, and allows users to download data and predict CDA using model.

Circ2DGNN: circRNA-disease Association Prediction via Transformer-based Graph Neural Network.

Investigating the associations between circRNA and diseases is vital for comprehending the underlying mechanisms of diseases and formulating effective therapies. Computational prediction methods often rely solely on known circRNA-disease data, indirectly incorporating other biomolecules' effects by computing circRNA and disease similarities based on these molecules. However, this approach is limited, as other biomolecules also play significant roles in circRNA-disease interactions. To address this, we construct a comprehensive heterogeneous network incorporating data on human circRNAs, diseases, and other biomolecule interactions to develop a novel computational model, circ2DGNN, which is built upon a heterogeneous graph neural network. circ2DGNN directly takes heterogeneous networks as inputs and obtains the embedded representation of each node for downstream link prediction through graph representation learning. circ2DGNN employs a Transformer-like architecture, which can compute heterogeneous attention score for each edge, and perform message propagation and aggregation, using a residual connection to enhance the representation vector. It uniquely applies the same parameter matrix only to identical meta-relationships, reflecting diverse parameter spaces for different relationship types. After fine-tuning hyperparameters via five-fold cross-validation, evaluation conducted on a test dataset shows circ2DGNN outperforms existing state-of-the-art(SOTA) methods.