Association Prediction Methods Research Articles

Gating-Enhanced Hierarchical Structure Learning in Hyperbolic Space and Multi-scale Neighbor Topology Learning in Euclidean Space for Prediction of Microbe-Drug Associations.

Identifying drug-related microbes may help us explore how the microbes affect the functions of drugs by promoting or inhibiting their effects. Most previous methods for the prediction of microbe-drug associations focused on integrating the attributes and topologies of microbe and drug nodes in Euclidean space. The heterogeneous network composed of microbes and drugs has a hierarchical structure, and the hyperbolic space is helpful for reflecting the structure. However, the previous methods did not fully exploit the structure. We propose a multi-space feature learning enhanced microbe-drug association prediction method, MFLP, to fuse the hierarchical structure of microbe and drug nodes in hyperbolic space and the multiscale neighbor topologies in Euclidean space. First, we project the nodes of the microbe-drug heterogeneous network on the sphere in hyperbolic space and then construct a topology which implies hierarchical structure and forms a hierarchical attribute embedding. The node information from multiple types of neighbor nodes with the new topological structure in the tangent plane space of a sphere is aggregated by the designed gating-enhanced hyperbolic graph neural network. Second, the gate at the node feature level is constructed to adaptively fuse the hierarchical features of microbe and drug nodes from two adjacent graph neural encoding layers. Third, multiple neighbor topological embeddings for each microbe and drug node are formed by neighborhood random walks on the microbe-drug heterogeneous network, and they cover neighborhood topologies with multiple scales, respectively. Finally, as each scale of topological embedding contains its specific neighborhood topology, we establish an independent graph convolutional neural network for the topology and form the topological representations of microbe and drug nodes in Euclidean space. The comparison experiments based on cross validation showed that MFLP outperformed several advanced prediction methods, and the ablation experiments verified the effectiveness of MFLP's major innovations. The case studies on three drugs further demonstrated MFLP's ability in being applied to discover potential candidate microbes for the given drugs.

Drug repositioning based on residual attention network and free multiscale adversarial training

BackgroundConducting traditional wet experiments to guide drug development is an expensive, time-consuming and risky process. Analyzing drug function and repositioning plays a key role in identifying new therapeutic potential of approved drugs and discovering therapeutic approaches for untreated diseases. Exploring drug-disease associations has far-reaching implications for identifying disease pathogenesis and treatment. However, reliable detection of drug-disease relationships via traditional methods is costly and slow. Therefore, investigations into computational methods for predicting drug-disease associations are currently needed.ResultsThis paper presents a novel drug-disease association prediction method, RAFGAE. First, RAFGAE integrates known associations between diseases and drugs into a bipartite network. Second, RAFGAE designs the Re_GAT framework, which includes multilayer graph attention networks (GATs) and two residual networks. The multilayer GATs are utilized for learning the node embeddings, which is achieved by aggregating information from multihop neighbors. The two residual networks are used to alleviate the deep network oversmoothing problem, and an attention mechanism is introduced to combine the node embeddings from different attention layers. Third, two graph autoencoders (GAEs) with collaborative training are constructed to simulate label propagation to predict potential associations. On this basis, free multiscale adversarial training (FMAT) is introduced. FMAT enhances node feature quality through small gradient adversarial perturbation iterations, improving the prediction performance. Finally, tenfold cross-validations on two benchmark datasets show that RAFGAE outperforms current methods. In addition, case studies have confirmed that RAFGAE can detect novel drug-disease associations.ConclusionsThe comprehensive experimental results validate the utility and accuracy of RAFGAE. We believe that this method may serve as an excellent predictor for identifying unobserved disease-drug associations.

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.

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.

GCNGAT: Drug–disease association prediction based on graph convolution neural network and graph attention network

Predicting drug–disease associations can contribute to discovering new therapeutic potentials of drugs, and providing important association information for new drug research and development. Many existing drug–disease association prediction methods have not distinguished relevant background information for the same drug targeted to different diseases. Therefore, this paper proposes a drug–disease association prediction model based on graph convolutional network and graph attention network (GCNGAT) to reposition marketed drugs under the distinguishment of background information. Firstly, in order to obtain initial drug–disease information, a drug–disease heterogeneous graph structure is constructed based on all known drug–disease associations. Secondly, based on the heterogeneous graph structure, the corresponding subgraphs of each group of drug–disease association pairs are extracted to distinguish different background information for the same drug from different diseases. Finally, a model combining Graph neural network with global Average pooling (GnnAp) is designed to predict potential drug–disease associations by learning drug–disease interaction feature representations. The experimental results show that adding subgraph extraction can effectively improve the prediction performance of the model, and the graph representation learning module can fully extract the deep features of drug–disease. Using the 5-fold cross-validation, the proposed model (GCNGAT) achieves AUC (Area Under the receiver operating characteristic Curve) values of 0.9182 and 0.9417 on the PREDICT dataset and CDataset dataset, respectively. Compared with other predictors on the same dataset (PREDICT dataset), GCNGAT outperforms the existing best-performing model (PSGCN), with a 1.58% increase in the AUC value. It is anticipated that this model can provide experimental reference for drug repositioning and further promote the drug research and development process.

Research on Efficient and Low-cost Drug-disease Association Prediction Method Based on Dual Attention in Heterogeneous Networks

Research on Efficient and Low-cost Drug-disease Association Prediction Method Based on Dual Attention in Heterogeneous Networks

MiGAP: miRNA–Gene Association Prediction Method Based on Deep Learning Model

MicroRNAs (miRNAs) are small RNA molecules consisting of approximately 22 nucleotides; they regulate gene expression and are employed in the development of therapeutics for intractable diseases. Predicting the association between miRNAs and genes is crucial for understanding their roles in molecular processes. miRNA–gene associations have been studied using deep learning methods, but these methods present various constraints. Through addressing the limitations of previous methods, this study aimed to achieve better performance than the state-of-the-art (SOTA) methods for studying miRNA–gene associations. We constructed the most extensive embedded dataset to date, comprising 717,728 miRNA–gene pairs, specifically designed for our deep learning model. Further, we applied an embedding method used for protein embedding for transforming our gene sequence data. Moreover, we constructed a sophisticated negative dataset based on three distance criteria, unlike most studies that randomly designate negative data. Leveraging the data and insights from these approaches, we built a deep learning model with the best performance among SOTA miRNA–gene studies (area under the receiver operating characteristic curve = 0.9834). In addition, we conducted a case study using the learned model to predict potential positive data. We also aimed to identify miRNAs closely associated with a gene linked to various cancers.

HGECDA: A Heterogeneous Graph Embedding Model for CircRNA-Disease Association Prediction.

Circular RNAs (circRNAs) are specifically and abnormally expressed in disease tissues, and thus can be used as biomarkers to diagnose relevant diseases. Predicting circRNA-disease associations will provide essential clues to reveal molecular mechanisms of disease development and discover novel therapeutic targets. Existing algorithms ignore the heterogeneous biological association information related to microRNAs (miRNAs). Based on a heterogeneous graph embedding model, a novel circRNA-disease association prediction method called HGECDA is developed in this paper. The heterogeneous graph network containing circRNA-miRNA-disease association information is first constructed. To sample the heterogeneous information, the meta-path-based random walk that can capture the relevance between various types of nodes is employed. Then, the path embedding model based on skip-gram and random negative sampling is built to acquire the initial feature vectors of circRNAs and diseases. Finally, the CosMulformer model with linearized self-attention and Hadamard product is designed to obtain the circRNA-disease interaction vectors and conduct the prediction task. Experimental results demonstrate the critical role of miRNA in enriching the information of the feature space, the effectiveness of the CosMulformer model in picking out deep local interaction features, and the feasibility of the Hadamard product chosen as the integration pattern in the CosMulformer model. Compared with existing state-of-the-art methods on the same dataset, HGECDA performs better than the other seven algorithms. Moreover, the case studies about breast cancer and colorectal cancer demonstrate the practical value of HGECDA in predicting potential circRNA-disease associations.

DEJKMDR: miRNA-disease association prediction method based on graph convolutional network.

Numerous studies have shown that miRNAs play a crucial role in the investigation of complex human diseases. Identifying the connection between miRNAs and diseases is crucial for advancing the treatment of complex diseases. However, traditional methods are frequently constrained by the small sample size and high cost, so computational simulations are urgently required to rapidly and accurately forecast the potential correlation between miRNA and disease. In this paper, the DEJKMDR, a graph convolutional network (GCN)-based miRNA-disease association prediction model is proposed. The novelty of this model lies in the fact that DEJKMDR integrates biomolecular information on miRNA and illness, including functional miRNA similarity, disease semantic similarity, and miRNA and disease similarity, according to their Gaussian interaction attribute. In order to minimize overfitting, some edges are randomly destroyed during the training phase after DropEdge has been used to regularize the edges. JK-Net, meanwhile, is employed to combine various domain scopes through the adaptive learning of nodes in various placements. The experimental results demonstrate that this strategy has superior accuracy and dependability than previous algorithms in terms of predicting an unknown miRNA-disease relationship. In a 10-fold cross-validation, the average AUC of DEJKMDR is determined to be 0.9772.

HGCLMDA: Predicting mRNA-Drug Sensitivity Associations via Hypergraph Contrastive Learning.

The identification of drug sensitivity to mRNA interactions is crucial for drug development and disease treatment, but traditional experimental methods for verifying mRNA-drug sensitivity associations are labor-intensive and time-consuming. In this study, we present a hypergraph contrastive learning approach, HGCLMDA, to predict potential mRNA-drug sensitivity associations. HGCLMDA integrates a graph convolutional network-based method with a hypergraph convolutional network to mine high-order relationships between mRNA-drug association pairs. The proposed cross-view contrastive learning architecture improves the model's learning ability, and the inner product is used to obtain the mRNA-drug sensitivity association score. Our experiments on three mRNA-drug sensitivity association data sets show that HGCLMDA outperforms traditional graph convolutional network-based methods, graph augmentation-based contrastive learning methods, and state-of-the-art association prediction methods. The visualization experiment demonstrates the strong discrimination ability of the mRNA and drug embeddings learned by HGCLMDA, and experiments on sparse data sets showcase the performance and robustness of the method. In-depth analysis of hypergraph structures reveals a crucial role that hypergraphs play in enhancing the performance of models. The case study highlights the potential of HGCLMDA as a valuable tool for predicting mRNA-drug sensitivity associations. The interpretive analysis reveals that HGCLMDA effectively models the similarity between mRNA-mRNA and drug-drug interactions.

Graph generative and adversarial strategy-enhanced node feature learning and self-calibrated pairwise attribute encoding for prediction of drug-related side effects.

Background: Inferring drug-related side effects is beneficial for reducing drug development cost and time. Current computational prediction methods have concentrated on graph reasoning over heterogeneous graphs comprising the drug and side effect nodes. However, the various topologies and node attributes within multiple drug-side effect heterogeneous graphs have not been completely exploited. Methods: We proposed a new drug-side effect association prediction method, GGSC, to deeply integrate the diverse topologies and attributes from multiple heterogeneous graphs and the self-calibration attributes of each drug-side effect node pair. First, we created two heterogeneous graphs comprising the drug and side effect nodes and their related similarity and association connections. Since each heterogeneous graph has its specific topology and node attributes, a node feature learning strategy was designed and the learning for each graph was enhanced from a graph generative and adversarial perspective. We constructed a generator based on a graph convolutional autoencoder to encode the topological structure and node attributes from the whole heterogeneous graph and then generate the node features embedding the graph topology. A discriminator based on multilayer perceptron was designed to distinguish the generated topological features from the original ones. We also designed representation-level attention to discriminate the contributions of topological representations from multiple heterogeneous graphs and adaptively fused them. Finally, we constructed a self-calibration module based on convolutional neural networks to guide pairwise attribute learning through the features of the small latent space. Results: The comparison experiment results showed that GGSC had higher prediction performance than several state-of-the-art prediction methods. The ablation experiments demonstrated the effectiveness of topological enhancement learning, representation-level attention, and self-calibrated pairwise attribute learning. In addition, case studies over five drugs demonstrated GGSC's ability in discovering the potential drug-related side effect candidates. Conclusion: We proposed a drug-side effect association prediction method, and the method is beneficial for screening the reliable association candidates for the biologists to discover the actual associations.

Drug-disease association prediction with literature based multi-feature fusion.

Introduction: Exploring the potential efficacy of a drug is a valid approach for drug development with shorter development times and lower costs. Recently, several computational drug repositioning methods have been introduced to learn multi-features for potential association prediction. However, fully leveraging the vast amount of information in the scientific literature to enhance drug-disease association prediction is a great challenge. Methods: We constructed a drug-disease association prediction method called Literature Based Multi-Feature Fusion (LBMFF), which effectively integrated known drugs, diseases, side effects and target associations from public databases as well as literature semantic features. Specifically, a pre-training and fine-tuning BERT model was introduced to extract literature semantic information for similarity assessment. Then, we revealed drug and disease embeddings from the constructed fusion similarity matrix by a graph convolutional network with an attention mechanism. Results: LBMFF achieved superior performance in drug-disease association prediction with an AUC value of 0.8818 and an AUPR value of 0.5916. Discussion: LBMFF achieved relative improvements of 31.67% and 16.09%, respectively, over the second-best results, compared to single feature methods and seven existing state-of-the-art prediction methods on the same test datasets. Meanwhile, case studies have verified that LBMFF can discover new associations to accelerate drug development. The proposed benchmark dataset and source code are available at: https://github.com/kang-hongyu/LBMFF.

LncRNA–disease association prediction method based on the nearest neighbor matrix completion model

State-of-the-art medical studies proved that long noncoding ribonucleic acids (lncRNAs) are closely related to various diseases. However, their large-scale detection in biological experiments is problematic and expensive. To aid screening and improve the efficiency of biological experiments, this study introduced a prediction model based on the nearest neighbor concept for lncRNA–disease association prediction. We used a new similarity algorithm in the model that fused potential associations. The experimental validation of the proposed algorithm proved its superiority over the available Cosine, Pearson, and Jaccard similarity algorithms. Satisfactory results in the comparative leave-one-out cross-validation test (with AUC = 0.96) confirmed its excellent predictive performance. Finally, the proposed model’s reliability was confirmed by performing predictions using a new dataset, yielding AUC = 0.92.

HLGNN-MDA: Heuristic Learning Based on Graph Neural Networks for miRNA-Disease Association Prediction.

Identifying disease-related miRNAs can improve the understanding of complex diseases. However, experimentally finding the association between miRNAs and diseases is expensive in terms of time and resources. The computational screening of reliable miRNA-disease associations has thus become a necessary tool to guide biological experiments. "Similar miRNAs will be associated with the same disease" is the assumption on which most current miRNA-disease association prediction methods rely; however, biased prior knowledge, and incomplete and inaccurate miRNA similarity data and disease similarity data limit the performance of the model. Here, we propose heuristic learning based on graph neural networks to predict microRNA-disease associations (HLGNN-MDA). We learn the local graph topology features of the predicted miRNA-disease node pairs using graph neural networks. In particular, our improvements to the graph convolution layer of the graph neural network enable it to learn information among homogeneous nodes and among heterogeneous nodes. We illustrate the performance of HLGNN-MDA by performing tenfold cross-validation against excellent baseline models. The results show that we have promising performance in multiple metrics. We also focus on the role of the improvements to the graph convolution layer in the model. The case studies are supported by evidence on breast cancer, hepatocellular carcinoma and renal cell carcinoma. Given the above, the experiments demonstrate that HLGNN-MDA can serve as a reliable method to identify novel miRNA-disease associations.

REDDA: Integrating multiple biological relations to heterogeneous graph neural network for drug-disease association prediction

Computational drug repositioning is an effective way to find new indications for existing drugs, thus can accelerate drug development and reduce experimental costs. Recently, various deep learning-based repurposing methods have been established to identify the potential drug-disease associations (DDA). However, effective utilization of the relations of biological entities to capture the biological interactions to enhance the drug-disease association prediction is still challenging. To resolve the above problem, we proposed a heterogeneous graph neural network called REDDA (Relations-Enhanced Drug-Disease Association prediction). Assembled with three attention mechanisms, REDDA can sequentially learn drug/disease representations by a general heterogeneous graph convolutional network-based node embedding block, a topological subnet embedding block, a graph attention block, and a layer attention block. Performance comparisons on our proposed benchmark dataset show that REDDA outperforms 8 advanced drug-disease association prediction methods, achieving relative improvements of 0.76% on the area under the receiver operating characteristic curve (AUC) score and 13.92% on the precision-recall curve (AUPR) score compared to the suboptimal method. On the other benchmark dataset, REDDA also obtains relative improvements of 2.48% on the AUC score and 4.93% on the AUPR score. Specifically, case studies also indicate that REDDA can give valid predictions for the discovery of -new indications for drugs and new therapies for diseases. The overall results provide an inspiring potential for REDDA in the in silico drug development. The proposed benchmark dataset and source code are available in https://github.com/gu-yaowen/REDDA.

LDAformer: predicting lncRNA-disease associations based on topological feature extraction and Transformer encoder.

The identification of long noncoding RNA (lncRNA)-disease associations is of great value for disease diagnosis and treatment, and it is now commonly used to predict potential lncRNA-disease associations with computational methods. However, the existing methods do not sufficiently extract key features during data processing, and the learning model parts are either less powerful or overly complex. Therefore, there is still potential to achieve better predictive performance by improving these two aspects. In this work, we propose a novel lncRNA-disease association prediction method LDAformer based on topological feature extraction and Transformer encoder. We construct the heterogeneous network by integrating the associations between lncRNAs, diseases and micro RNAs (miRNAs). Intra-class similarities and inter-class associations are presented as the lncRNA-disease-miRNA weighted adjacency matrix to unify semantics. Next, we design a topological feature extraction process to further obtain multi-hop topological pathway features latent in the adjacency matrix. Finally, to capture the interdependencies between heterogeneous pathways, a Transformer encoder based on the global self-attention mechanism is employed to predict lncRNA-disease associations. The efficient feature extraction and the intuitive and powerful learning model lead to ideal performance. The results of computational experiments on two datasets show that our method outperforms the state-of-the-art baseline methods. Additionally, case studies further indicate its capability to discover new associations accurately.

Predict potential miRNA-disease associations based on bounded nuclear norm regularization

Increasing evidences show that the abnormal microRNA (miRNA) expression is related to a variety of complex human diseases. However, the current biological experiments to determine miRNA-disease associations are time consuming and expensive. Therefore, computational models to predict potential miRNA-disease associations are in urgent need. Though many miRNA-disease association prediction methods have been proposed, there is still a room to improve the prediction accuracy. In this paper, we propose a matrix completion model with bounded nuclear norm regularization to predict potential miRNA-disease associations, which is called BNNRMDA. BNNRMDA at first constructs a heterogeneous miRNA-disease network integrating the information of miRNA self-similarity, disease self-similarity, and the known miRNA-disease associations, which is represented by an adjacent matrix. Then, it models the miRNA-disease prediction as a relaxed matrix completion with error tolerance, value boundary and nuclear norm minimization. Finally it implements the alternating direction method to solve the matrix completion problem. BNNRMDA makes full use of available information of miRNAs and diseases, and can deals with the data containing noise. Compared with four state-of-the-art methods, the experimental results show BNNRMDA achieved the best performance in five-fold cross-validation and leave-one-out cross-validation. The case studies on two complex human diseases showed that 47 of the top 50 prediction results of BNNRMDA have been verified in the latest HMDD database.

Leveraging big data analytics in 5G‐enabled IoT and industrial IoT for the development of sustainable smart cities

AbstractThere has been an exponential growth in the number of low‐cost heterogeneous sensor devices that are connected to the internet in the existing infrastructure of smart cities in the past decade. These sensors and actuator devices are employed in various industries to collect invaluable data that greatly impacts business decisions. State‐of‐the‐art research is being carried out to process the high‐volume data collected in high velocity streams with high variability in order to draw meaningful insights to cater to business needs in various domains. Big data analytics finds diversified opportunities in 5G‐enabled Internet of Things (IoT) and industrial IoT environment to study the data patterns and produce new results which provides big organizations a conducive environment to take informed decisions. This article presents an exhaustive investigation of the various applications and algorithms of the big data analytics in 5G‐driven IoT and industrial IoT systems with a detailed taxonomy of the existing analytical systems and also the challenges specific to the applications in an IoT environment. A holistic understanding on the importance of security and privacy of big data during the development of smart city infrastructure in high velocity streaming process has been explained for a broad understanding of the big data streaming processes. A thorough analysis of important data mining algorithms such as classification, association rule mining, clustering, and prediction methods for big IoT data from the recent literature also has been presented to provide a clear understanding of existing issues in handling big data in 5G‐enabled IoT for the development of sustainable smart city infrastructure.

Network-Based Approaches for Disease-Gene Association Prediction Using Protein-Protein Interaction Networks

Genome-wide association studies (GWAS) can be used to infer genome intervals that are involved in genetic diseases. However, investigating a large number of putative mutations for GWAS is resource- and time-intensive. Network-based computational approaches are being used for efficient disease-gene association prediction. Network-based methods are based on the underlying assumption that the genes causing the same diseases are located close to each other in a molecular network, such as a protein-protein interaction (PPI) network. In this survey, we provide an overview of network-based disease-gene association prediction methods based on three categories: graph-theoretic algorithms, machine learning algorithms, and an integration of these two. We experimented with six selected methods to compare their prediction performance using a heterogeneous network constructed by combining a genome-wide weighted PPI network, an ontology-based disease network, and disease-gene associations. The experiment was conducted in two different settings according to the presence and absence of known disease-associated genes. The results revealed that HerGePred, an integrative method, outperformed in the presence of known disease-associated genes, whereas PRINCE, which adopted a network propagation algorithm, was the most competitive in the absence of known disease-associated genes. Overall, the results demonstrated that the integrative methods performed better than the methods using graph-theory only, and the methods using a heterogeneous network performed better than those using a homogeneous PPI network only.

Integration of Neighbor Topologies Based on Meta-Paths and Node Attributes for Predicting Drug-Related Diseases.

Identifying new disease indications for existing drugs can help facilitate drug development and reduce development cost. The previous drug–disease association prediction methods focused on data about drugs and diseases from multiple sources. However, they did not deeply integrate the neighbor topological information of drug and disease nodes from various meta-path perspectives. We propose a prediction method called NAPred to encode and integrate meta-path-level neighbor topologies, multiple kinds of drug attributes, and drug-related and disease-related similarities and associations. The multiple kinds of similarities between drugs reflect the degrees of similarity between two drugs from different perspectives. Therefore, we constructed three drug–disease heterogeneous networks according to these drug similarities, respectively. A learning framework based on fully connected neural networks and a convolutional neural network with an attention mechanism is proposed to learn information of the neighbor nodes of a pair of drug and disease nodes. The multiple neighbor sets composed of different kinds of nodes were formed respectively based on meta-paths with different semantics and different scales. We established the attention mechanisms at the neighbor-scale level and at the neighbor topology level to learn enhanced neighbor feature representations and enhanced neighbor topological representations. A convolutional-autoencoder-based module is proposed to encode the attributes of the drug–disease pair in three heterogeneous networks. Extensive experimental results indicated that NAPred outperformed several state-of-the-art methods for drug–disease association prediction, and the improved recall rates demonstrated that NAPred was able to retrieve more actual drug–disease associations from the top-ranked candidates. Case studies on five drugs further demonstrated the ability of NAPred to identify potential drug-related disease candidates.