lncRNA-disease Associations Research Articles

LDAGM: prediction lncRNA-disease asociations by graph convolutional auto-encoder and multilayer perceptron based on multi-view heterogeneous networks

BackgroundLong non-coding RNAs (lncRNAs) can prevent, diagnose, and treat a variety of complex human diseases, and it is crucial to establish a method to efficiently predict lncRNA-disease associations.ResultsIn this paper, we propose a prediction method for the lncRNA-disease association relationship, named LDAGM, which is based on the Graph Convolutional Autoencoder and Multilayer Perceptron model. The method first extracts the functional similarity and Gaussian interaction profile kernel similarity of lncRNAs and miRNAs, as well as the semantic similarity and Gaussian interaction profile kernel similarity of diseases. It then constructs six homogeneous networks and deeply fuses them using a deep topology feature extraction method. The fused networks facilitate feature complementation and deep mining of the original association relationships, capturing the deep connections between nodes. Next, by combining the obtained deep topological features with the similarity network of lncRNA, disease, and miRNA interactions, we construct a multi-view heterogeneous network model. The Graph Convolutional Autoencoder is employed for nonlinear feature extraction. Finally, the extracted nonlinear features are combined with the deep topological features of the multi-view heterogeneous network to obtain the final feature representation of the lncRNA-disease pair. Prediction of the lncRNA-disease association relationship is performed using the Multilayer Perceptron model. To enhance the performance and stability of the Multilayer Perceptron model, we introduce a hidden layer called the aggregation layer in the Multilayer Perceptron model. Through a gate mechanism, it controls the flow of information between each hidden layer in the Multilayer Perceptron model, aiming to achieve optimal feature extraction from each hidden layer.ConclusionsParameter analysis, ablation studies, and comparison experiments verified the effectiveness of this method, and case studies verified the accuracy of this method in predicting lncRNA-disease association relationships.

ACLNDA: an asymmetric graph contrastive learning framework for predicting noncoding RNA-disease associations in heterogeneous graphs.

Noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), play crucial roles in gene expression regulation and are significant in disease associations and medical research. Accurate ncRNA-disease association prediction is essential for understanding disease mechanisms and developing treatments. Existing methods often focus on single tasks like lncRNA-disease associations (LDAs), miRNA-disease associations (MDAs), or lncRNA-miRNA interactions (LMIs), and fail to exploit heterogeneous graph characteristics. We propose ACLNDA, an asymmetric graph contrastive learning framework for analyzing heterophilic ncRNA-disease associations. It constructs inter-layer adjacency matrices from the original lncRNA, miRNA, and disease associations, and uses a Top-K intra-layer similarity edges construction approach to form a triple-layer heterogeneous graph. Unlike traditional works, to account for both node attribute features (ncRNA/disease) and node preference features (association), ACLNDA employs an asymmetric yet simple graph contrastive learning framework to maximize one-hop neighborhood context and two-hop similarity, extracting ncRNA-disease features without relying on graph augmentations or homophily assumptions, reducing computational cost while preserving data integrity. Our framework is capable of being applied to a universal range of potential LDA, MDA, and LMI association predictions. Further experimental results demonstrate superior performance to other existing state-of-the-art baseline methods, which shows its potential for providing insights into disease diagnosis and therapeutic target identification. The source code and data of ACLNDA is publicly available at https://github.com/AI4Bread/ACLNDA.

IGATTLDA: Integrative graph attention and transformer-based model for predicting lncRNA-Disease associations.

Long non-coding RNAs (lncRNAs) have emerged as significant contributors to the regulation of various biological processes, and their dysregulation has been linked to a variety of human disorders. Accurate prediction of potential correlations between lncRNAs and diseases is crucial for advancing disease diagnostics and treatment procedures. The authors introduced a novel computational method, iGATTLDA, for the prediction of lncRNA-disease associations. The model utilised lncRNA and disease similarity matrices, with known associations represented in an adjacency matrix. A heterogeneous network was constructed, dissecting lncRNAs and diseases as nodes and their associations as edges. The Graph Attention Network (GAT) is employed to process initial features and corresponding adjacency information. GAT identified significant neighbouring nodes in the network, capturing intricate relationships between lncRNAs and diseases, and generating new feature representations. Subsequently, the transformer captures global dependencies and interactions across the entire sequence of features produced by the GAT. Consequently, iGATTLDA successfully captures complex relationships and interactions that conventional approaches may overlook. In evaluating iGATTLDA, it attained an area under the receiver operating characteristic (ROC) curve (AUC) of 0.95 and an area under the precision recall curve (AUPRC) of 0.96 with a two-layer multilayer perceptron (MLP) classifier. These results were notably higher compared to the majority of previously proposed models, further substantiating the model's efficiency in predicting potential lncRNA-disease associations by incorporating both local and global interactions. The implementation details can be obtained from https://github.com/momanyibiffon/iGATTLDA.

Mask-Guided Target Node Feature Learning and Dynamic Detailed Feature Enhancement for lncRNA-Disease Association Prediction.

Identifying new relevant long noncoding RNAs (lncRNAs) for various human diseases can facilitate the exploration of the causes and progression of these diseases. Recently, several graph inference methods have been proposed to predict disease-related lncRNAs by exploiting the topological structure and node attributes within graphs. However, these methods did not prioritize the target lncRNA and disease nodes over auxiliary nodes like miRNA nodes, potentially limiting their ability to fully utilize the features of the target nodes. We propose a new method, mask-guided target node feature learning and dynamic detailed feature enhancement for lncRNA-disease association prediction (MDLD), to enhance node feature learning for improved lncRNA-disease association prediction. First, we designed a heterogeneous graph masked transformer autoencoder to guide feature learning, focusing more on the features of target lncRNA (disease) nodes. The target nodes were increasingly masked as training progressed, which helps develop a more robust prediction model. Second, we developed a graph convolutional network with dynamic residuals (GCNDR) to learn and integrate the heterogeneous topology and features of all lncRNA, disease, and miRNA nodes. GCNDR employs an interlayer residual strategy and a residual evolution strategy to mitigate oversmoothing caused by multilayer graph convolution. The interlayer residual strategy estimates the importance of node features learned in the previous GCN encoding layer for nodes in the current encoding layer. Additionally, since there are dependencies in the importance of features of individual lncRNA (disease, miRNA) nodes across multiple encoding layers, a gated recurrent unit-based strategy is proposed to encode these dependencies. Finally, we designed a perspective-level attention mechanism to obtain more informative features of lncRNA and disease node pairs from the perspectives of mask-enhanced and dynamic-enhanced node features. Cross-validation experimental results demonstrated that MDLD outperformed 10 other state-of-the-art prediction methods. Ablation experiments and case studies on candidate lncRNAs for three diseases further proved the technical contributions of MDLD and its capability to discover disease-related lncRNAs.

Predicting lncRNA-Disease Associations Based on a Dual-Path Feature Extraction Network with Multiple Sources of Information Integration.

Identifying the associations between long noncoding RNAs (lncRNAs) and disease is critical for disease prevention, diagnosis and treatment. However, conducting wet experiments to discover these associations is time-consuming and costly. Therefore, computational modeling for predicting lncRNA-disease associations (LDAs) has become an important alternative. To enhance the accuracy of LDAs prediction and alleviate the issue of node feature oversmoothing when exploring the potential features of nodes using graph neural networks, we introduce DPFELDA, a dual-path feature extraction network that leverages the integration of information from multiple sources to predict LDA. Initially, we establish a dual-view structure of lncRNAs and disease and a heterogeneous network of lncRNA-disease-microRNA (miRNA) interactions. Subsequently, features are extracted using a dual-path feature extraction network. In particular, we employ a combination of a graph convolutional network, a convolutional block attention module, and a node aggregation layer to perform multilayer topology feature extraction for the dual-view structure of lncRNAs and diseases. Additionally, we utilize a Transformer model to construct the node topology feature residual network for obtaining node-specific features in heterogeneous networks. Finally, XGBoost is employed for LDA prediction. The experimental results demonstrate that DPFELDA outperforms the benchmark model on various benchmark data sets. In the course of model exploration, it becomes evident that DPFELDA successfully alleviates the issue of node feature oversmoothing induced by graph-based learning. Ablation experiments confirm the effectiveness of the innovative module, and a case study substantiates the accuracy of DPFELDA model in predicting novel LDAs for characteristic diseases.

HPTRMF: Collaborative Matrix Factorization-Based Prediction Method for LncRNA-Disease Associations Using High-Order Perturbation and Flexible Trifactor Regularization.

Existing matrix factorization methods face challenges, including the cold start problem and global nonlinear data loss during similarity learning, particularly in predicting associations between long noncoding RNAs (LncRNAs) and diseases. To overcome these issues, we introduce HPTRMF, a matrix factorization approach incorporating high-order perturbation and flexible trifactor regularization. HPTRMF constructs a high-order correlation matrix utilizing the known association matrix, leveraging high-order perturbation to effectively address the cold start problem caused by data sparsity. Additionally, HPTRMF incorporates a flexible trifactor regularization term to capture similarity information on LncRNAs and diseases, enabling the effective handling of global nonlinear data loss by capturing such data in the similarity matrix. Experimental results demonstrate the superiority of HPTRMF over nine state-of-the-art algorithms in Leave-One-Out Cross-Validation (LOOCV) and Five-Fold Cross-Validation (5-Fold CV) on three data sets.HPTRMF and data sets are available in https://github.com/Llvvvv/HPTRMF.

Developing explainable models for lncRNA-Targeted drug discovery using graph autoencoders

The application of explainable artificial intelligence technology is crucial in lncRNA-targeted drug discovery, given lncRNA’s role in regulating a broad spectrum of diseases, including cancer. Current advanced deep learning models efficiently predict the association between lncRNA and disease, facilitating the discovery of potential lncRNA-targeted drug. However, these models have notable limitations, including a tendency to overfit due to their focus on integrating various similarity networks for feature extraction of lncRNA and diseases. Additionally, they employ complex classifiers to predict unknown lncRNA-disease associations (LDAs), resulting in reduced interpretability. We designed an explainable model named EM-LTDD, utilizing graph autoencoders (GAE) and self-supervised learning strategies, aimed at identifying potential drugs targeting lncRNA. The EM-LTDD model improves self-supervised training by employing a novel strategy that masks parts of the known lncRNA-disease network. This approach not only enhances the model’s interpretability but also mitigates the impact of noise. Furthermore, the EM-LTDD model reconstructs the lncRNA-disease network with a robust collaborative decoder, minimizing information loss caused by occlusion and improving node representation. Experimental results demonstrate the effectiveness of our model compared to existing leading models, promising to significantly aid in the discovery and design of lncRNA-targeted drugs. Our code and data are available at: https://github.com/huiyingliulevy/EM-LTDD.

Neighborhood based computational approaches for the prediction of lncRNA-disease associations

MotivationLong non-coding RNAs (lncRNAs) are a class of molecules involved in important biological processes. Extensive efforts have been provided to get deeper understanding of disease mechanisms at the lncRNA level, guiding towards the detection of biomarkers for disease diagnosis, treatment, prognosis and prevention. Unfortunately, due to costs and time complexity, the number of possible disease-related lncRNAs verified by traditional biological experiments is very limited. Computational approaches for the prediction of disease-lncRNA associations allow to identify the most promising candidates to be verified in laboratory, reducing costs and time consuming.ResultsWe propose novel approaches for the prediction of lncRNA-disease associations, all sharing the idea of exploring associations among lncRNAs, other intermediate molecules (e.g., miRNAs) and diseases, suitably represented by tripartite graphs. Indeed, while only a few lncRNA-disease associations are still known, plenty of interactions between lncRNAs and other molecules, as well as associations of the latters with diseases, are available. A first approach presented here, NGH, relies on neighborhood analysis performed on a tripartite graph, built upon lncRNAs, miRNAs and diseases. A second approach (CF) relies on collaborative filtering; a third approach (NGH-CF) is obtained boosting NGH by collaborative filtering. The proposed approaches have been validated on both synthetic and real data, and compared against other methods from the literature. It results that neighborhood analysis allows to outperform competitors, and when it is combined with collaborative filtering the prediction accuracy further improves, scoring a value of AUC equal to 0966.AvailabilitySource code and sample datasets are available at: https://github.com/marybonomo/LDAsPredictionApproaches.git

GEnDDn: An lncRNA-Disease Association Identification Framework Based on Dual-Net Neural Architecture and Deep Neural Network.

Accumulating studies have demonstrated close relationships between long non-coding RNAs (lncRNAs) and diseases. Identification of new lncRNA-disease associations (LDAs) enables us to better understand disease mechanisms and further provides promising insights into cancer targeted therapy and anti-cancer drug design. Here, we present an LDA prediction framework called GEnDDn based on deep learning. GEnDDn mainly comprises two steps: First, features of both lncRNAs and diseases are extracted by combining similarity computation, non-negative matrix factorization, and graph attention auto-encoder, respectively. And each lncRNA-disease pair (LDP) is depicted as a vector based on concatenation operation on the extracted features. Subsequently, unknown LDPs are classified by aggregating dual-net neural architecture and deep neural network. Using six different evaluation metrics, we found that GEnDDn surpassed four competing LDA identification methods (SDLDA, LDNFSGB, IPCARF, LDASR) on the lncRNADisease and MNDR databases under fivefold cross-validation experiments on lncRNAs, diseases, LDPs, and independent lncRNAs and independent diseases, respectively. Ablation experiments further validated the powerful LDA prediction performance of GEnDDn. Furthermore, we utilized GEnDDn to find underlying lncRNAs for lung cancer and breast cancer. The results elucidated that there may be dense linkages between IFNG-AS1 and lung cancer as well as between HIF1A-AS1 and breast cancer. The results require further biomedical experimental verification. GEnDDn is publicly available at https://github.com/plhhnu/GEnDDn.

Similarity-guided graph contrastive learning for lncRNA-disease association prediction

The increasing research evidence indicates that long non-coding RNAs (lncRNAs) play important roles in regulating biological processes and are closely associated with many human diseases. Computational methods have emerged as indispensable tools for identifying associations between long non-coding RNA (lncRNA) and diseases, primarily due to the time-consuming and costly nature of traditional biological experiments. Given the scarcity of verified lncRNA-disease associations, the intensifying focus on deep learning is playing a crucial role in refining the accuracy of predictive models. Moreover, the contrastive learning method exhibits a clear advantage in situations where data is scarce or annotation costs are high. In this paper, we leverage the advantages of graph neural networks and contrastive learning to innovatively propose a similarity-guided graph contrastive learning (SGGCL) model for predicting lncRNA-disease associations. In the SGGCL model, we employ a novel similarity-guided graph data augmentation method to generate high-quality positive and negative sample pairs, addressing the scarcity of verified data. Additionally, we utilize the RWR algorithm and a graph convolutional neural network for contrastive learning, facilitating the capture of global topology and high-level node embeddings. The experimental results on several datasets demonstrate the superior predictive performance and scalability of our method in lncRNA-disease association prediction compared to state-of-the-art methods.

NFMCLDA: Predicting miRNA-based lncRNA-disease associations by network fusion and matrix completion

In recent years, emerging evidence has revealed a strong association between dysregulations of long non-coding RNAs (lncRNAs) and sophisticated human diseases. Biological experiments are adequate to identify such associations, but they are costly and time-consuming. Therefore, developing high-quality computational methods is a challenging and urgent task in the field of bioinformatics. This paper proposes a new lncRNA-disease association inference approach NFMCLDA (Network Fusion and Matrix Completion lncRNA-Disease Association), which can effectively integrate multi-source association data. In this approach, miRNA information is used as the transition path, and an unbalanced random walk method on three-layer heterogeneous network is adopted in the preprocessing. Therefore, more effective information between networks can be mined and the sparsity problem of the association matrix can be solved. Finally, the matrix completion method accurately predicts associations. The results show that NFMCLDA can provide more accurate lncRNA-disease associations than state-of-the-art methods. The areas under the receiver operating characteristic curves are 0.9648 and 0.9713, respectively, through the cross-validation of 5-fold and 10-fold. Data from published case studies on four diseases - lung cancer, osteosarcoma, cervical cancer, and colon cancer - have confirmed the reliable predictive potential of NFMCLDA model.

Learning Association Characteristics by Dynamic Hypergraph and Gated Convolution Enhanced Pairwise Attributes for Prediction of Disease-Related lncRNAs.

As the long non-coding RNAs (lncRNAs) play important roles during the incurrence and development of various human diseases, identifying disease-related lncRNAs can contribute to clarifying the pathogenesis of diseases. Most of the recent lncRNA-disease association prediction methods utilized the multi-source data about the lncRNAs and diseases. A single lncRNA may participate in multiple disease processes, and multiple lncRNAs usually are involved in the same disease process synergistically. However, the previous methods did not completely exploit the biological characteristics to construct the informative prediction models. We construct a prediction model based on adaptive hypergraph and gated convolution for lncRNA-disease association prediction (AGLDA), to embed and encode the biological characteristics about lncRNA-disease associations, the topological features from the entire heterogeneous graph perspective, and the gated enhanced pairwise features. First, the strategy for constructing hyperedges is designed to reflect the biological characteristic that multiple lncRNAs are involved in multiple disease processes. Furthermore, each hyperedge has its own biological perspective, and multiple hyperedges are beneficial for revealing the diverse relationships among multiple lncRNAs and diseases. Second, we encode the biological features of each lncRNA (disease) node using a strategy based on dynamic hypergraph convolutional networks. The strategy may adaptively learn the features of the hyperedges and formulate the dynamically evolved hypergraph topological structure. Third, a group convolutional network is established to integrate the entire heterogeneous topological structure and multiple types of node attributes within an lncRNA-disease-miRNA graph. Finally, a gated convolutional strategy is proposed to enhance the informative features of the lncRNA-disease node pairs. The comparison experiments indicate that AGLDA outperforms seven advanced prediction methods. The ablation studies confirm the effectiveness of major innovations, and the case studies validate AGLDA's ability in application for discovering potential disease-related lncRNA candidates.

Prediction of lncRNA and disease associations based on residual graph convolutional networks with attention mechanism

LncRNAs are non-coding RNAs with a length of more than 200 nucleotides. More and more evidence shows that lncRNAs are inextricably linked with diseases. To make up for the shortcomings of traditional methods, researchers began to collect relevant biological data in the database and used bioinformatics prediction tools to predict the associations between lncRNAs and diseases, which greatly improved the efficiency of the study. To improve the prediction accuracy of current methods, we propose a new lncRNA-disease associations prediction method with attention mechanism, called ResGCN-A. Firstly, we integrated lncRNA functional similarity, lncRNA Gaussian interaction profile kernel similarity, disease semantic similarity, and disease Gaussian interaction profile kernel similarity to obtain lncRNA comprehensive similarity and disease comprehensive similarity. Secondly, the residual graph convolutional network was used to extract the local features of lncRNAs and diseases. Thirdly, the new attention mechanism was used to assign the weight of the above features to further obtain the potential features of lncRNAs and diseases. Finally, the training set required by the Extra-Trees classifier was obtained by concatenating potential features, and the potential associations between lncRNAs and diseases were obtained by the trained Extra-Trees classifier. ResGCN-A combines the residual graph convolutional network with the attention mechanism to realize the local and global features fusion of lncRNA and diseases, which is beneficial to obtain more accurate features and improve the prediction accuracy. In the experiment, ResGCN-A was compared with five other methods through 5-fold cross-validation. The results show that the AUC value and AUPR value obtained by ResGCN-A are 0.9916 and 0.9951, which are superior to the other five methods. In addition, case studies and robustness evaluation have shown that ResGCN-A is an effective method for predicting lncRNA-disease associations. The source code for ResGCN-A will be available at https://github.com/Wangxiuxiun/ResGCN-A.

Finding potential lncRNA-disease associations using a boosting-based ensemble learning model.

Introduction: Long non-coding RNAs (lncRNAs) have been in the clinical use as potential prognostic biomarkers of various types of cancer. Identifying associations between lncRNAs and diseases helps capture the potential biomarkers and design efficient therapeutic options for diseases. Wet experiments for identifying these associations are costly and laborious. Methods: We developed LDA-SABC, a novel boosting-based framework for lncRNA-disease association (LDA) prediction. LDA-SABC extracts LDA features based on singular value decomposition (SVD) and classifies lncRNA-disease pairs (LDPs) by incorporating LightGBM and AdaBoost into the convolutional neural network. Results: The LDA-SABC performance was evaluated under five-fold cross validations (CVs) on lncRNAs, diseases, and LDPs. It obviously outperformed four other classical LDA inference methods (SDLDA, LDNFSGB, LDASR, and IPCAF) through precision, recall, accuracy, F1 score, AUC, and AUPR. Based on the accurate LDA prediction performance of LDA-SABC, we used it to find potential lncRNA biomarkers for lung cancer. The results elucidated that 7SK and HULC could have a relationship with non-small-cell lung cancer (NSCLC) and lung adenocarcinoma (LUAD), respectively. Conclusion: We hope that our proposed LDA-SABC method can help improve the LDA identification.

Predicting lncRNA-disease associations using multiple metapaths in hierarchical graph attention networks

BackgroundMany biological studies have shown that lncRNAs regulate the expression of epigenetically related genes. The study of lncRNAs has helped to deepen our understanding of the pathogenesis of complex diseases at the molecular level. Due to the large number of lncRNAs and the complex and time-consuming nature of biological experiments, applying computer techniques to predict potential lncRNA-disease associations is very effective. To explore information between complex network structures, existing methods rely mainly on lncRNA and disease information. Metapaths have been applied to network models as an effective method for exploring information in heterogeneous graphs. However, existing methods are dominated by lncRNAs or disease nodes and tend to ignore the paths provided by intermediate nodes.MethodsWe propose a deep learning model based on hierarchical graphical attention networks to predict unknown lncRNA-disease associations using multiple types of metapaths to extract features. We have named this model the MMHGAN. First, the model constructs a lncRNA-disease–miRNA heterogeneous graph based on known associations and two homogeneous graphs of lncRNAs and diseases. Second, for homogeneous graphs, the features of neighboring nodes are aggregated using a multihead attention mechanism. Third, for the heterogeneous graph, metapaths of different intermediate nodes are selected to construct subgraphs, and the importance of different types of metapaths is calculated and aggregated to obtain the final embedded features. Finally, the features are reconstructed using a fully connected layer to obtain the prediction results.ResultsWe used a fivefold cross-validation method and obtained an average AUC value of 96.07% and an average AUPR value of 93.23%. Additionally, ablation experiments demonstrated the role of homogeneous graphs and different intermediate node path weights. In addition, we studied lung cancer, esophageal carcinoma, and breast cancer. Among the 15 lncRNAs associated with these diseases, 15, 12, and 14 lncRNAs were validated by the lncRNA Disease Database and the Lnc2Cancer Database, respectively. ConclusionWe compared the MMHGAN model with six existing models with better performance, and the case study demonstrated that the model was effective in predicting the correlation between potential lncRNAs and diseases.

Node-adaptive graph Transformer with structural encoding for accurate and robust lncRNA-disease association prediction

BackgroundLong noncoding RNAs (lncRNAs) are integral to a plethora of critical cellular biological processes, including the regulation of gene expression, cell differentiation, and the development of tumors and cancers. Predicting the relationships between lncRNAs and diseases can contribute to a better understanding of the pathogenic mechanisms of disease and provide strong support for the development of advanced treatment methods.ResultsTherefore, we present an innovative Node-Adaptive Graph Transformer model for predicting unknown LncRNA-Disease Associations, named NAGTLDA. First, we utilize the node-adaptive feature smoothing (NAFS) method to learn the local feature information of nodes and encode the structural information of the fusion similarity network of diseases and lncRNAs using Structural Deep Network Embedding (SDNE). Next, the Transformer module is used to capture potential association information between the network nodes. Finally, we employ a Transformer module with two multi-headed attention layers for learning global-level embedding fusion. Network structure coding is added as the structural inductive bias of the network to compensate for the missing message-passing mechanism in Transformer. NAGTLDA achieved an average AUC of 0.9531 and AUPR of 0.9537 significantly higher than state-of-the-art methods in 5-fold cross validation. We perform case studies on 4 diseases; 55 out of 60 associations between lncRNAs and diseases have been validated in the literatures. The results demonstrate the enormous potential of the graph Transformer structure to incorporate graph structural information for uncovering lncRNA-disease unknown correlations.ConclusionsOur proposed NAGTLDA model can serve as a highly efficient computational method for predicting biological information associations.

Applying negative sample denoising and multi-view feature for lncRNA-disease association prediction.

Increasing evidence indicates that mutations and dysregulation of long non-coding RNA (lncRNA) play a crucial role in the pathogenesis and prognosis of complex human diseases. Computational methods for predicting the association between lncRNAs and diseases have gained increasing attention. However, these methods face two key challenges: obtaining reliable negative samples and incorporating lncRNA-disease association (LDA) information from multiple perspectives. This paper proposes a method called NDMLDA, which combines multi-view feature extraction, unsupervised negative sample denoising, and stacking ensemble classifier. Firstly, an unsupervised method (K-means) is used to design a negative sample denoising module to alleviate the imbalance of samples and the impact of potential noise in the negative samples on model performance. Secondly, graph attention networks are employed to extract multi-view features of both lncRNAs and diseases, thereby enhancing the learning of association information between them. Finally, lncRNA-disease association prediction is implemented through a stacking ensemble classifier. Existing research datasets are integrated to evaluate performance, and 5-fold cross-validation is conducted on this dataset. Experimental results demonstrate that NDMLDA achieves an AUC of 0.9907and an AUPR of 0.9927, with a 5-fold cross-validation variance of less than 0.1%. These results outperform the baseline methods. Additionally, case studies further illustrate the model's potential in cancer diagnosis and precision medicine implementation.

GCNFORMER: graph convolutional network and transformer for predicting lncRNA-disease associations.

A growing body of researches indicate that the disrupted expression of long non-coding RNA (lncRNA) is linked to a range of human disorders. Therefore, the effective prediction of lncRNA-disease association (LDA) can not only suggest solutions to diagnose a condition but also save significant time and labor costs. In this work, we proposed a novel LDA predicting algorithm based on graph convolutional network and transformer, named GCNFORMER. Firstly, we integrated the intraclass similarity and interclass connections between miRNAs, lncRNAs and diseases, and built a graph adjacency matrix. Secondly, to completely obtain the features between various nodes, we employed a graph convolutional network for feature extraction. Finally, to obtain the global dependencies between inputs and outputs, we used a transformer encoder with a multiheaded attention mechanism to forecast lncRNA-disease associations. The results of fivefold cross-validation experiment on the public dataset revealed that the AUC and AUPR of GCNFORMER achieved 0.9739 and 0.9812, respectively. We compared GCNFORMER with six advanced LDA prediction models, and the results indicated its superiority over the other six models. Furthermore, GCNFORMER's effectiveness in predicting potential LDAs is underscored by case studies on breast cancer, colon cancer and lung cancer. The combination of graph convolutional network and transformer can effectively improve the performance of LDA prediction model and promote the in-depth development of this research filed.

Self-Supervised Contrastive Learning on Attribute and Topology Graphs for Predicting Relationships Among lncRNAs, miRNAs and Diseases.

Exploring potential association between long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and diseases is an essential part of prevention, diagnosis and treatment of diseases. Since determining these relationships experimentally is resource-intensive and time-consuming, therefore computational methods have emerged as an attractive way to address this issue. However, existing computational approaches for inferring lncRNA-disease associations (LDA), miRNA-disease associations (MDA) and lncRNA-miRNA interactions (LMI) tend to focus on single task, neglecting the benefits of leveraging multiple biomolecular interactions and domain-specific knowledge for multi-task prediction. Furthermore, labeled data for LDA, MDA and LMI is scarce and costly in real-word applications, making it challenging for models to learn comprehensive node embedding patterns. Building on our previous work, this paper proposes a multi-task prediction model (called SSCLMD) that employs self-supervised contrastive learning on attribute and topology graphs to identify potential LDAs, MDAs and LMIs. Specifically, firstly, domain knowledge of lncRNAs, miRNAs and diseases as well as their interactions are exploited to construct attribute graph and topology graph, respectively. Then, the nodes are encoded in the attribute and topology spaces to extract the specific and common feature. Meanwhile, the attention mechanism is performed to adaptively fuse the embedding from different views. SSCLMD incorporates a contrastive self-supervised learning task as a regularize to guide the learning of node embeddings in both attribute and topology space without relying on labels. Severing as a regularize in multi-task learning paradigm, it to improves the model's generalization capabilities. Extensive experiments on 2 manually curated datasets demonstrate that SSCLMD significantly outperforms other baseline methods in LDA, MDA and LMI prediction tasks. Additionally, case studies on both new and old datasets further supported the ability of SSCLMD to uncover novel disease-related lncRNAs and miRNAs. The source codes and supplementary file of this work are publicly available on \url{https://github.com/sheng-n/SSCLMD}.

HRGCNLDA: Forecasting of lncRNA-disease association based on hierarchical refinement graph convolutional neural network.

Long non-coding RNA (lncRNA) is considered to be a crucial regulator involved in various human biological processes, including the regulation of tumor immune checkpoint proteins. It has great potential as both a cancer biomolecular biomarker and therapeutic target. Nevertheless, conventional biological experimental techniques are both resource-intensive and laborious, making it essential to develop an accurate and efficient computational method to facilitate the discovery of potential links between lncRNAs and diseases. In this study, we proposed HRGCNLDA, a computational approach utilizing hierarchical refinement of graph convolutional neural networks for forecasting lncRNA-disease potential associations. This approach effectively addresses the over-smoothing problem that arises from stacking multiple layers of graph convolutional neural networks. Specifically, HRGCNLDA enhances the layer representation during message propagation and node updates, thereby amplifying the contribution of hidden layers that resemble the ego layer while reducing discrepancies. The results of the experiments showed that HRGCNLDA achieved the highest AUC-ROC (area under the receiver operating characteristic curve, AUC for short) and AUC-PR (area under the precision versus recall curve, AUPR for short) values compared to other methods. Finally, to further demonstrate the reliability and efficacy of our approach, we performed case studies on the case of three prevalent human diseases, namely, breast cancer, lung cancer and gastric cancer.