Dataset Information

Graph Convolutional Network and Convolutional Neural Network Based Method for Predicting lncRNA-Disease Associations.

ABSTRACT: Aberrant expressions of long non-coding RNAs (lncRNAs) are often associated with diseases and identification of disease-related lncRNAs is helpful for elucidating complex pathogenesis. Recent methods for predicting associations between lncRNAs and diseases integrate their pertinent heterogeneous data. However, they failed to deeply integrate topological information of heterogeneous network comprising lncRNAs, diseases, and miRNAs. We proposed a novel method based on the graph convolutional network and convolutional neural network, referred to as GCNLDA, to infer disease-related lncRNA candidates. The heterogeneous network containing the lncRNA, disease, and miRNA nodes, is constructed firstly. The embedding matrix of a lncRNA-disease node pair was constructed according to various biological premises about lncRNAs, diseases, and miRNAs. A new framework based on a graph convolutional network and a convolutional neural network was developed to learn network and local representations of the lncRNA-disease pair. On the left side of the framework, the autoencoder based on graph convolution deeply integrated topological information within the heterogeneous lncRNA-disease-miRNA network. Moreover, as different node features have discriminative contributions to the association prediction, an attention mechanism at node feature level is constructed. The left side learnt the network representation of the lncRNA-disease pair. The convolutional neural networks on the right side of the framework learnt the local representation of the lncRNA-disease pair by focusing on the similarities, associations, and interactions that are only related to the pair. Compared to several state-of-the-art prediction methods, GCNLDA had superior performance. Case studies on stomach cancer, osteosarcoma, and lung cancer confirmed that GCNLDA effectively discovers the potential lncRNA-disease associations.

SUBMITTER: Xuan P

PROVIDER: S-EPMC6769579 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

Graph Convolutional Network and Convolutional Neural Network Based Method for Predicting lncRNA-Disease Associations.

Xuan Ping P Pan Shuxiang S Zhang Tiangang T Liu Yong Y Sun Hao H

Cells 20190830 9

Aberrant expressions of long non-coding RNAs (lncRNAs) are often associated with diseases and identification of disease-related lncRNAs is helpful for elucidating complex pathogenesis. Recent methods for predicting associations between lncRNAs and diseases integrate their pertinent heterogeneous data. However, they failed to deeply integrate topological information of heterogeneous network comprising lncRNAs, diseases, and miRNAs. We proposed a novel method based on the graph convolutional netwo ...[more]

PMID: 31480350

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Project description:It is well known that the unusual expression of long non-coding RNAs (lncRNAs) is closely related to the physiological and pathological processes of diseases. Therefore, inferring the potential lncRNA-disease associations are helpful for understanding the molecular pathogenesis of diseases. Most previous methods have concentrated on the construction of shallow learning models in order to predict lncRNA-disease associations, while they have failed to deeply integrate heterogeneous multi-source data and to learn the low-dimensional feature representations from these data. We propose a method based on the convolutional neural network with the attention mechanism and convolutional autoencoder for predicting candidate disease-related lncRNAs, and refer to it as CNNDLP. CNNDLP integrates multiple kinds of data from heterogeneous sources, including the associations, interactions, and similarities related to the lncRNAs, diseases, and miRNAs. Two different embedding layers are established by combining the diverse biological premises about the cases that the lncRNAs are likely to associate with the diseases. We construct a novel prediction model based on the convolutional neural network with attention mechanism and convolutional autoencoder to learn the attention and the low-dimensional network representations of the lncRNA-disease pairs from the embedding layers. The different adjacent edges among the lncRNA, miRNA, and disease nodes have different contributions for association prediction. Hence, an attention mechanism at the adjacent edge level is established, and the left side of the model learns the attention representation of a pair of lncRNA and disease. A new type of lncRNA similarity and a new type of disease similarity are calculated by incorporating the topological structures of multiple bipartite networks. The low-dimensional network representation of the lncRNA-disease pairs is further learned by the autoencoder based convolutional neutral network on the right side of the model. The cross-validation experimental results confirm that CNNDLP has superior prediction performance compared to the state-of-the-art methods. Case studies on stomach cancer, breast cancer, and prostate cancer further show the ability of CNNDLP for discovering the potential disease lncRNAs.

Project description:Numerous evidences indicate that Circular RNAs (circRNAs) are widely involved in the occurrence and development of diseases. Identifying the association between circRNAs and diseases plays a crucial role in exploring the pathogenesis of complex diseases and improving the diagnosis and treatment of diseases. However, due to the complex mechanisms between circRNAs and diseases, it is expensive and time-consuming to discover the new circRNA-disease associations by biological experiment. Therefore, there is increasingly urgent need for utilizing the computational methods to predict novel circRNA-disease associations. In this study, we propose a computational method called GCNCDA based on the deep learning Fast learning with Graph Convolutional Networks (FastGCN) algorithm to predict the potential disease-associated circRNAs. Specifically, the method first forms the unified descriptor by fusing disease semantic similarity information, disease and circRNA Gaussian Interaction Profile (GIP) kernel similarity information based on known circRNA-disease associations. The FastGCN algorithm is then used to objectively extract the high-level features contained in the fusion descriptor. Finally, the new circRNA-disease associations are accurately predicted by the Forest by Penalizing Attributes (Forest PA) classifier. The 5-fold cross-validation experiment of GCNCDA achieved 91.2% accuracy with 92.78% sensitivity at the AUC of 90.90% on circR2Disease benchmark dataset. In comparison with different classifier models, feature extraction models and other state-of-the-art methods, GCNCDA shows strong competitiveness. Furthermore, we conducted case study experiments on diseases including breast cancer, glioma and colorectal cancer. The results showed that 16, 15 and 17 of the top 20 candidate circRNAs with the highest prediction scores were respectively confirmed by relevant literature and databases. These results suggest that GCNCDA can effectively predict potential circRNA-disease associations and provide highly credible candidates for biological experiments.

Project description:BackgroundThe existing studies show that circRNAs can be used as a biomarker of diseases and play a prominent role in the treatment and diagnosis of diseases. However, the relationships between the vast majority of circRNAs and diseases are still unclear, and more experiments are needed to study the mechanism of circRNAs. Nowadays, some scholars use the attributes between circRNAs and diseases to study and predict their associations. Nonetheless, most of the existing experimental methods use less information about the attributes of circRNAs, which has a certain impact on the accuracy of the final prediction results. On the other hand, some scholars also apply experimental methods to predict the associations between circRNAs and diseases. But such methods are usually expensive and time-consuming. Based on the above shortcomings, follow-up research is needed to propose a more efficient calculation-based method to predict the associations between circRNAs and diseases.ResultsIn this study, a novel algorithm (method) is proposed, which is based on the Graph Convolutional Network (GCN) constructed with Random Walk with Restart (RWR) and Principal Component Analysis (PCA) to predict the associations between circRNAs and diseases (CRPGCN). In the construction of CRPGCN, the RWR algorithm is used to improve the similarity associations of the computed nodes with their neighbours. After that, the PCA method is used to dimensionality reduction and extract features, it makes the connection between circRNAs with higher similarity and diseases closer. Finally, The GCN algorithm is used to learn the features between circRNAs and diseases and calculate the final similarity scores, and the learning datas are constructed from the adjacency matrix, similarity matrix and feature matrix as a heterogeneous adjacency matrix and a heterogeneous feature matrix.ConclusionsAfter 2-fold cross-validation, 5-fold cross-validation and 10-fold cross-validation, the area under the ROC curve of the CRPGCN is 0.9490, 0.9720 and 0.9722, respectively. The CRPGCN method has a valuable effect in predict the associations between circRNAs and diseases.

Project description:A lot of studies indicated that aberrant expression of long non-coding RNA genes (lncRNAs) is closely related to human diseases. Identifying disease-related lncRNAs (disease lncRNAs) is critical for understanding the pathogenesis and etiology of diseases. Most of the previous methods focus on prioritizing the potential disease lncRNAs based on shallow learning methods. The methods fail to extract the deep and complex feature representations of lncRNA-disease associations. Furthermore, nearly all the methods ignore the discriminative contributions of the similarity, association, and interaction relationships among lncRNAs, disease, and miRNAs for the association prediction. A dual convolutional neural networks with attention mechanisms based method is presented for predicting the candidate disease lncRNAs, and it is referred to as CNNLDA. CNNLDA deeply integrates the multiple source data like the lncRNA similarities, the disease similarities, the lncRNA-disease associations, the lncRNA-miRNA interactions, and the miRNA-disease associations. The diverse biological premises about lncRNAs, miRNAs, and diseases are combined to construct the feature matrix from the biological perspectives. A novel framework based on the dual convolutional neural networks is developed to learn the global and attention representations of the lncRNA-disease associations. The left part of the framework exploits the various information contained by the feature matrix to learn the global representation of lncRNA-disease associations. The different connection relationships among the lncRNA, miRNA, and disease nodes and the different features of these nodes have the discriminative contributions for the association prediction. Hence we present the attention mechanisms from the relationship level and the feature level respectively, and the right part of the framework learns the attention representation of associations. The experimental results based on the cross validation indicate that CNNLDA yields superior performance than several state-of-the-art methods. Case studies on stomach cancer, lung cancer, and colon cancer further demonstrate CNNLDA's ability to discover the potential disease lncRNAs.

Dataset Information

Graph Convolutional Network and Convolutional Neural Network Based Method for Predicting lncRNA-Disease Associations.

Publications

Graph Convolutional Network and Convolutional Neural Network Based Method for Predicting lncRNA-Disease Associations.

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