Clustering on heterogeneous IoT information network based on meta path.

As the Internet and Internet of Things (IoT) continue to develop, Heterogeneous Information Networks (HIN) have formed complex interaction relationships among data objects. These relationships are represented by various types of edges (meta-paths) that contain rich semantic information. In the context of IoT data applications, the widespread adoption of Trigger-Action Patterns makes the management and analysis of heterogeneous data particularly important. This study proposes a meta-path-based clustering method for heterogeneous IoT data called I-RankClus, which aims to improve the modeling and analysis efficiency of IoT data. By combining ranking with clustering algorithms, the PageRank algorithm was used to calculate the intraclass influence of objects in the network. The HITS algorithm then transfers the influence to the core objects, thereby optimizing the classification of objects during the clustering process. The I-RankClus algorithm does not process each meta-path individually, but instead integrates multiple meta-paths to enhance the interpretability and clustering performance of the model. The experimental results show that the I-RankClus algorithm can process complex IoT datasets more effectively than traditional clustering methods and provide more accurate clustering outcomes. Furthermore, through a detailed analysis of meta-paths, this study explored the influence and importance of different meta-paths, thereby validating the effectiveness of the algorithm. Overall, the research presented in this paper not only improves the application effects of HINs in IoT data analysis but also provides valuable methods and insights for future network data processing.

MPHGCL-DDI: Meta-Path-Based Heterogeneous Graph Contrastive Learning for Drug-Drug Interaction Prediction.

The combinatorial therapy with multiple drugs may lead to unexpected drug-drug interactions (DDIs) and result in adverse reactions to patients. Predicting DDI events can mitigate the potential risks of combinatorial therapy and enhance drug safety. In recent years, deep models based on heterogeneous graph representation learning have attracted widespread interest in DDI event prediction and have yielded satisfactory results, but there is still room for improvement in prediction performance. In this study, we proposed a meta-path-based heterogeneous graph contrastive learning model, MPHGCL-DDI, for DDI event prediction. The model constructs two contrastive views based on meta-paths: an average graph view and an augmented graph view. The former represents that there are connections between drugs, while the latter reveals how the drugs connect with each other. We defined three levels of data augmentation schemes in the augmented graph view and adopted a combination of three losses in the model training phase: multi-relation prediction loss, unsupervised contrastive loss and supervised contrastive loss. Furthermore, the model incorporates indirect drug information, protein-protein interactions (PPIs), to reveal latent relations of drugs. We evaluated MPHGCL-DDI on three different tasks of two datasets. Experimental results demonstrate that MPHGCL-DDI surpasses several state-of-the-art methods in performance.

MGCNSS: miRNA-disease association prediction with multi-layer graph convolution and distance-based negative sample selection strategy.

Identifying disease-associated microRNAs (miRNAs) could help understand the deep mechanism of diseases, which promotes the development of new medicine. Recently, network-based approaches have been widely proposed for inferring the potential associations between miRNAs and diseases. However, these approaches ignore the importance of different relations in meta-paths when learning the embeddings of miRNAs and diseases. Besides, they pay little attention to screening out reliable negative samples which is crucial for improving the prediction accuracy. In this study, we propose a novel approach named MGCNSS with the multi-layer graph convolution and high-quality negative sample selection strategy. Specifically, MGCNSS first constructs a comprehensive heterogeneous network by integrating miRNA and disease similarity networks coupled with their known association relationships. Then, we employ the multi-layer graph convolution to automatically capture the meta-path relations with different lengths in the heterogeneous network and learn the discriminative representations of miRNAs and diseases. After that, MGCNSS establishes a highly reliable negative sample set from the unlabeled sample set with the negative distance-based sample selection strategy. Finally, we train MGCNSS under an unsupervised learning manner and predict the potential associations between miRNAs and diseases. The experimental results fully demonstrate that MGCNSS outperforms all baseline methods on both balanced and imbalanced datasets. More importantly, we conduct case studies on colon neoplasms and esophageal neoplasms, further confirming the ability of MGCNSS to detect potential candidate miRNAs. The source code is publicly available on GitHub https://github.com/15136943622/MGCNSS/tree/master.

Revisiting multi-view learning: A perspective of implicitly heterogeneous Graph Convolutional Network.

Graph Convolutional Network (GCN) has become a hotspot in graph-based machine learning due to its powerful graph processing capability. Most of the existing GCN-based approaches are designed for single-view data. In numerous practical scenarios, data is expressed through multiple views, rather than a single view. The ability of GCN to model homogeneous graphs is indisputable, while it is insufficient in facing the heterophily property of multi-view data. In this paper, we revisit multi-view learning to propose an implicit heterogeneous graph convolutional network that efficiently captures the heterogeneity of multi-view data while exploiting the powerful feature aggregation capability of GCN. We automatically assign optimal importance to each view when constructing the meta-path graph. High-order cross-view meta-paths are explored based on the obtained graph, and a series of graph matrices are generated. Combining graph matrices with learnable global feature representation to obtain heterogeneous graph embeddings at various levels. Finally, in order to effectively utilize both local and global information, we introduce a graph-level attention mechanism at the meta-path level that allocates private information to each node individually. Extensive experimental results convincingly support the superior performance of the proposed method compared to other state-of-the-art approaches.

PCDA-HNMP: Predicting circRNA-disease association using heterogeneous network and meta-path.

Increasing amounts of experimental studies have shown that circular RNAs (circRNAs) play important regulatory roles in human diseases through interactions with related microRNAs (miRNAs). CircRNAs have become new potential disease biomarkers and therapeutic targets. Predicting circRNA-disease association (CDA) is of great significance for exploring the pathogenesis of complex diseases, which can improve the diagnosis level of diseases and promote the targeted therapy of diseases. However, determination of CDAs through traditional clinical trials is usually time-consuming and expensive. Computational methods are now alternative ways to predict CDAs. In this study, a new computational method, named PCDA-HNMP, was designed. For obtaining informative features of circRNAs and diseases, a heterogeneous network was first constructed, which defined circRNAs, mRNAs, miRNAs and diseases as nodes and associations between them as edges. Then, a deep analysis was conducted on the heterogeneous network by extracting meta-paths connecting to circRNAs (diseases), thereby mining hidden associations between various circRNAs (diseases). These associations constituted the meta-path-induced networks for circRNAs and diseases. The features of circRNAs and diseases were derived from the aforementioned networks via mashup. On the other hand, miRNA-disease associations (mDAs) were employed to improve the model's performance. miRNA features were yielded from the meta-path-induced networks on miRNAs and circRNAs, which were constructed from the meta-paths connecting miRNAs and circRNAs in the heterogeneous network. A concatenation operation was adopted to build the features of CDAs and mDAs. Such representations of CDAs and mDAs were fed into XGBoost to set up the model. The five-fold cross-validation yielded an area under the curve (AUC) of 0.9846, which was better than those of some existing state-of-the-art methods. The employment of mDAs can really enhance the model's performance and the importance analysis on meta-path-induced networks shown that networks produced by the meta-paths containing validated CDAs provided the most important contributions.

MPCLCDA: predicting circRNA-disease associations by using automatically selected meta-path and contrastive learning.

Circular RNA (circRNA) is closely associated with human diseases. Accordingly, identifying the associations between human diseases and circRNA can help in disease prevention, diagnosis and treatment. Traditional methods are time consuming and laborious. Meanwhile, computational models can effectively predict potential circRNA-disease associations (CDAs), but are restricted by limited data, resulting in data with high dimension and imbalance. In this study, we propose a model based on automatically selected meta-path and contrastive learning, called the MPCLCDA model. First, the model constructs a new heterogeneous network based on circRNA similarity, disease similarity and known association, via automatically selected meta-path and obtains the low-dimensional fusion features of nodes via graph convolutional networks. Then, contrastive learning is used to optimize the fusion features further, and obtain the node features that make the distinction between positive and negative samples more evident. Finally, circRNA-disease scores are predicted through a multilayer perceptron. The proposed method is compared with advanced methods on four datasets. The average area under the receiver operating characteristic curve, area under the precision-recall curve and F1 score under 5-fold cross-validation reached 0.9752, 0.9831 and 0.9745, respectively. Simultaneously, case studies on human diseases further prove the predictive ability and application value of this method.

On QSAR-based cardiotoxicity modeling with the expressiveness-enhanced graph learning model and dual-threshold scheme.

Introduction: Given the direct association with malignant ventricular arrhythmias, cardiotoxicity is a major concern in drug design. In the past decades, computational models based on the quantitative structure-activity relationship have been proposed to screen out cardiotoxic compounds and have shown promising results. The combination of molecular fingerprint and the machine learning model shows stable performance for a wide spectrum of problems; however, not long after the advent of the graph neural network (GNN) deep learning model and its variant (e.g., graph transformer), it has become the principal way of quantitative structure-activity relationship-based modeling for its high flexibility in feature extraction and decision rule generation. Despite all these progresses, the expressiveness (the ability of a program to identify non-isomorphic graph structures) of the GNN model is bounded by the WL isomorphism test, and a suitable thresholding scheme that relates directly to the sensitivity and credibility of a model is still an open question. Methods: In this research, we further improved the expressiveness of the GNN model by introducing the substructure-aware bias by the graph subgraph transformer network model. Moreover, to propose the most appropriate thresholding scheme, a comprehensive comparison of the thresholding schemes was conducted. Results: Based on these improvements, the best model attains performance with 90.4% precision, 90.4% recall, and 90.5% F1-score with a dual-threshold scheme (active: <1µM; non-active: >30µM). The improved pipeline (graph subgraph transformer network model and thresholding scheme) also shows its advantages in terms of the activity cliff problem and model interpretability.

Improving drug-drug interactions prediction with interpretability via meta-path-based information fusion.

Drug-drug interactions (DDIs) are compound effects when patients take two or more drugs at the same time, which may weaken the efficacy of drugs or cause unexpected side effects. Thus, accurately predicting DDIs is of great significance for the drug development and the drug safety surveillance. Although many methods have been proposed for the task, the biological knowledge related to DDIs is not fully utilized and the complex semantics among drug-related biological entities are not effectively captured in existing methods, leading to suboptimal performance. Moreover, the lack of interpretability for the predicted results also limits the wide application of existing methods for DDIs prediction. In this study, we propose a novel framework for predicting DDIs with interpretability. Specifically, we construct a heterogeneous information network (HIN) by explicitly utilizing the biological knowledge related to the procedure of inducing DDIs. To capture the complex semantics in HIN, a meta-path-based information fusion mechanism is proposed to learn high-quality representations of drugs. In addition, an attention mechanism is designed to combine semantic information obtained from meta-paths with different lengths to obtain final representations of drugs for DDIs prediction. Comprehensive experiments are conducted on 2410 approved drugs, and the results of predictive performance comparison show that our proposed framework outperforms selected representative baselines on the task of DDIs prediction. The results of ablation study and cold-start scenario indicate that the meta-path-based information fusion mechanism red is beneficial for capturing the complex semantics among drug-related biological entities. Moreover, the results of case study demonstrate that the designed attention mechanism is able to provide partial interpretability for the predicted DDIs. Therefore, the proposed method will be a feasible solution to the task of predicting DDIs.

Meta-path guided graph attention network for explainable herb recommendation.

Traditional Chinese Medicine (TCM) has been widely adopted in clinical practice by Eastern Asia people for thousands of years. Nowadays, TCM still plays a critical role in Chinese society and receives increasing attention worldwide. The existing herb recommenders learn the complex relations between symptoms and herbs by mining the TCM prescriptions. Given a set of symptoms, they will provide a set of herbs and explanations from the TCM theory. However, the foundation of TCM is Yinyangism (i.e. the combination of Five Phases theory with Yin-yang theory), which is very different from modern medicine philosophy. Only recommending herbs from the TCM theory aspect largely prevents TCM from modern medical treatment. As TCM and modern medicine share a common view at the molecular level, it is necessary to integrate the ancient practice of TCM and standards of modern medicine. In this paper, we explore the underlying action mechanisms of herbs from both TCM and modern medicine, and propose a Meta-path guided Graph Attention Network (MGAT) to provide the explainable herb recommendations. Technically, to translate TCM from an experience-based medicine to an evidence-based medicine system, we incorporate the pharmacology knowledge of modern Chinese medicine with the TCM knowledge. We design a meta-path guided information propagation scheme based on the extended knowledge graph, which combines information propagation and decision process. This scheme adopts meta-paths (predefined relation sequences) to guide neighbor selection in the propagation process. Furthermore, the attention mechanism is utilized in aggregation to help distinguish the salience of different paths connecting a symptom with a herb. In this way, our model can distill the long-range semantics along meta-paths and generate fine-grained explanations. We conduct extensive experiments on a public TCM dataset, demonstrating comparable performance to the state-of-the-art herb recommendation models and the strong explainability.

DeepMPF: deep learning framework for predicting drug-target interactions based on multi-modal representation with meta-path semantic analysis.

BACKGROUND: Drug-target interaction (DTI) prediction has become a crucial prerequisite in drug design and drug discovery. However, the traditional biological experiment is time-consuming and expensive, as there are abundant complex interactions present in the large size of genomic and chemical spaces. For alleviating this phenomenon, plenty of computational methods are conducted to effectively complement biological experiments and narrow the search spaces into a preferred candidate domain. Whereas, most of the previous approaches cannot fully consider association behavior semantic information based on several schemas to represent complex the structure of heterogeneous biological networks. Additionally, the prediction of DTI based on single modalities cannot satisfy the demand for prediction accuracy. METHODS: We propose a multi-modal representation framework of 'DeepMPF' based on meta-path semantic analysis, which effectively utilizes heterogeneous information to predict DTI. Specifically, we first construct protein-drug-disease heterogeneous networks composed of three entities. Then the feature information is obtained under three views, containing sequence modality, heterogeneous structure modality and similarity modality. We proposed six representative schemas of meta-path to preserve the high-order nonlinear structure and catch hidden structural information of the heterogeneous network. Finally, DeepMPF generates highly representative comprehensive feature descriptors and calculates the probability of interaction through joint learning. RESULTS: To evaluate the predictive performance of DeepMPF, comparison experiments are conducted on four gold datasets. Our method can obtain competitive performance in all datasets. We also explore the influence of the different feature embedding dimensions, learning strategies and classification methods. Meaningfully, the drug repositioning experiments on COVID-19 and HIV demonstrate DeepMPF can be applied to solve problems in reality and help drug discovery. The further analysis of molecular docking experiments enhances the credibility of the drug candidates predicted by DeepMPF. CONCLUSIONS: All the results demonstrate the effectively predictive capability of DeepMPF for drug-target interactions. It can be utilized as a useful tool to prescreen the most potential drug candidates for the protein. The web server of the DeepMPF predictor is freely available at http://120.77.11.78/DeepMPF/ , which can help relevant researchers to further study.

Multi-view contrastive heterogeneous graph attention network for lncRNA-disease association prediction.

MOTIVATION: Exploring the potential long noncoding RNA (lncRNA)-disease associations (LDAs) plays a critical role for understanding disease etiology and pathogenesis. Given the high cost of biological experiments, developing a computational method is a practical necessity to effectively accelerate experimental screening process of candidate LDAs. However, under the high sparsity of LDA dataset, many computational models hardly exploit enough knowledge to learn comprehensive patterns of node representations. Moreover, although the metapath-based GNN has been recently introduced into LDA prediction, it discards intermediate nodes along the meta-path and results in information loss. RESULTS: This paper presents a new multi-view contrastive heterogeneous graph attention network (GAT) for lncRNA-disease association prediction, MCHNLDA for brevity. Specifically, MCHNLDA firstly leverages rich biological data sources of lncRNA, gene and disease to construct two-view graphs, feature structural graph of feature schema view and lncRNA-gene-disease heterogeneous graph of network topology view. Then, we design a cross-contrastive learning task to collaboratively guide graph embeddings of the two views without relying on any labels. In this way, we can pull closer the nodes of similar features and network topology, and push other nodes away. Furthermore, we propose a heterogeneous contextual GAT, where long short-term memory network is incorporated into attention mechanism to effectively capture sequential structure information along the meta-path. Extensive experimental comparisons against several state-of-the-art methods show the effectiveness of proposed framework.The code and data of proposed framework is freely available at https://github.com/zhaoxs686/MCHNLDA.

Improving therapeutic synergy score predictions with adverse effects using multi-task heterogeneous network learning.

Drug combinations could trigger pharmacological therapeutic effects (TEs) and adverse effects (AEs). Many computational methods have been developed to predict TEs, e.g. the therapeutic synergy scores of anti-cancer drug combinations, or AEs from drug-drug interactions. However, most of the methods treated the AEs and TEs predictions as two separate tasks, ignoring the potential mechanistic commonalities shared between them. Based on previous clinical observations, we hypothesized that by learning the shared mechanistic commonalities between AEs and TEs, we could learn the underlying MoAs (mechanisms of actions) and ultimately improve the accuracy of TE predictions. To test our hypothesis, we formulated the TE prediction problem as a multi-task heterogeneous network learning problem that performed TE and AE learning tasks simultaneously. To solve this problem, we proposed Muthene (multi-task heterogeneous network embedding) and evaluated it on our collected drug-drug interaction dataset with both TEs and AEs indications. Our experimental results showed that, by including the AE prediction as an auxiliary task, Muthene generated more accurate TE predictions than standard single-task learning methods, which supports our hypothesis. Using a drug pair Vincristine-Dasatinib as a case study, we demonstrated that our method not only provides a novel way of TE predictions but also helps us gain a deeper understanding of the MoAs of drug combinations.

MVNMDA: A Multi-View Network Combing Semantic and Global Features for Predicting miRNA-Disease Association.

A growing body of experimental evidence suggests that microRNAs (miRNAs) are closely associated with specific human diseases and play critical roles in their development and progression. Therefore, identifying miRNA related to specific diseases is of great significance for disease screening and treatment. In the early stages, the identification of associations between miRNAs and diseases demanded laborious and time-consuming biological experiments that often carried a substantial risk of failure. With the exponential growth in the number of potential miRNA-disease association combinations, traditional biological experimental methods face difficulties in processing massive amounts of data. Hence, developing more efficient computational methods to predict possible miRNA-disease associations and prioritize them is particularly necessary. In recent years, numerous deep learning-based computational methods have been developed and have demonstrated excellent performance. However, most of these methods rely on external databases or tools to compute various auxiliary information. Unfortunately, these external databases or tools often cover only a limited portion of miRNAs and diseases, resulting in many miRNAs and diseases being unable to match with these computational methods. Therefore, there are certain limitations associated with the practical application of these methods. To overcome the above limitations, this study proposes a multi-view computational model called MVNMDA, which predicts potential miRNA-disease associations by integrating features of miRNA and diseases from local views, global views, and semantic views. Specifically, MVNMDA utilizes known association information to construct node initial features. Then, multiple networks are constructed based on known association to extract low-dimensional feature embedding of all nodes. Finally, a cascaded attention classifier is proposed to fuse features from coarse to fine, suppressing noise within the features and making precise predictions. To validate the effectiveness of the proposed method, extensive experiments were conducted on the HMDD v2.0 and HMDD v3.2 datasets. The experimental results demonstrate that MVNMDA achieves better performance compared to other computational methods. Additionally, the case study results further demonstrate the reliable predictive performance of MVNMDA.

RLFDDA: a meta-path based graph representation learning model for drug-disease association prediction.

BACKGROUND: Drug repositioning is a very important task that provides critical information for exploring the potential efficacy of drugs. Yet developing computational models that can effectively predict drug-disease associations (DDAs) is still a challenging task. Previous studies suggest that the accuracy of DDA prediction can be improved by integrating different types of biological features. But how to conduct an effective integration remains a challenging problem for accurately discovering new indications for approved drugs. METHODS: In this paper, we propose a novel meta-path based graph representation learning model, namely RLFDDA, to predict potential DDAs on heterogeneous biological networks. RLFDDA first calculates drug-drug similarities and disease-disease similarities as the intrinsic biological features of drugs and diseases. A heterogeneous network is then constructed by integrating DDAs, disease-protein associations and drug-protein associations. With such a network, RLFDDA adopts a meta-path random walk model to learn the latent representations of drugs and diseases, which are concatenated to construct joint representations of drug-disease associations. As the last step, we employ the random forest classifier to predict potential DDAs with their joint representations. RESULTS: To demonstrate the effectiveness of RLFDDA, we have conducted a series of experiments on two benchmark datasets by following a ten-fold cross-validation scheme. The results show that RLFDDA yields the best performance in terms of AUC and F1-score when compared with several state-of-the-art DDAs prediction models. We have also conducted a case study on two common diseases, i.e., paclitaxel and lung tumors, and found that 7 out of top-10 diseases and 8 out of top-10 drugs have already been validated for paclitaxel and lung tumors respectively with literature evidence. Hence, the promising performance of RLFDDA may provide a new perspective for novel DDAs discovery over heterogeneous networks.

Exploiting Dual-Attention Networks for Explainable Recommendation in Heterogeneous Information Networks.

The aim of explainable recommendation is not only to provide recommended items to users, but also to make users aware of why these items are recommended. Traditional recommendation methods infer user preferences for items using user-item rating information. However, the expressive power of latent representations of users and items is relatively limited due to the sparseness of the user-item rating matrix. Heterogeneous information networks (HIN) provide contextual information for improving recommendation performance and interpreting the interactions between users and items. However, due to the heterogeneity and complexity of context information in HIN, it is still a challenge to integrate this contextual information into explainable recommendation systems effectively. In this paper, we propose a novel framework-the dual-attention networks for explainable recommendation (DANER) in HINs. We first used multiple meta-paths to capture high-order semantic relations between users and items in HIN for generating similarity matrices, and then utilized matrix decomposition on similarity matrices to obtain low-dimensional sparse representations of users and items. Secondly, we introduced two-level attention networks, namely a local attention network and a global attention network, to integrate the representations of users and items from different meta-paths for obtaining high-quality representations. Finally, we use a standard multi-layer perceptron to model the interactions between users and items, which predict users' ratings of items. Furthermore, the dual-attention mechanism also contributes to identifying critical meta-paths to generate relevant explanations for users. Comprehensive experiments on two real-world datasets demonstrate the effectiveness of DANER on recommendation performance as compared with the state-of-the-art methods. A case study illustrates the interpretability of DANER.

Learning global dependencies and multi-semantics within heterogeneous graph for predicting disease-related lncRNAs.

MOTIVATION: Long noncoding RNAs (lncRNAs) play an important role in the occurrence and development of diseases. Predicting disease-related lncRNAs can help to understand the pathogenesis of diseases deeply. The existing methods mainly rely on multi-source data related to lncRNAs and diseases when predicting the associations between lncRNAs and diseases. There are interdependencies among node attributes in a heterogeneous graph composed of all lncRNAs, diseases and micro RNAs. The meta-paths composed of various connections between them also contain rich semantic information. However, the existing methods neglect to integrate attribute information of intermediate nodes in meta-paths. RESULTS: We propose a novel association prediction model, GSMV, to learn and deeply integrate the global dependencies, semantic information of meta-paths and node-pair multi-view features related to lncRNAs and diseases. We firstly formulate the global representations of the lncRNA and disease nodes by establishing a self-attention mechanism to capture and learn the global dependencies among node attributes. Second, starting from the lncRNA and disease nodes, respectively, multiple meta-pathways are established to reveal different semantic information. Considering that each meta-path contains specific semantics and has multiple meta-path instances which have different contributions to revealing meta-path semantics, we design a graph neural network based module which consists of a meta-path instance encoding strategy and two novel attention mechanisms. The proposed meta-path instance encoding strategy is used to learn the contextual connections between nodes within a meta-path instance. One of the two new attention mechanisms is at the meta-path instance level, which learns rich and informative meta-path instances. The other attention mechanism integrates various semantic information from multiple meta-paths to learn the semantic representation of lncRNA and disease nodes. Finally, a dilated convolution-based learning module with adjustable receptive fields is proposed to learn multi-view features of lncRNA-disease node pairs. The experimental results prove that our method outperforms seven state-of-the-art comparing methods for lncRNA-disease association prediction. Ablation experiments demonstrate the contributions of the proposed global representation learning, semantic information learning, pairwise multi-view feature learning and the meta-path instance encoding strategy. Case studies on three cancers further demonstrate our method's ability to discover potential disease-related lncRNA candidates. CONTACT: zhang@hlju.edu.cn or peiliangwu@ysu.edu.cn. SUPPLEMENTARY INFORMATION: Supplementary data are available at Briefings in Bioinformatics online.

Latent neighborhood-based heterogeneous graph representation.

Graph, as a powerful data structure, has shown superior capability on modeling complex systems. Since real-world objects and their interactions are often multi-modal and multi-typed, compared with traditional homogeneous graphs, heterogeneous graphs can represent real-world objects more effectively. Meanwhile, rich semantic information brings great challenges for learning heterogeneous graph representation (HGR). Most existing HGR methods are based on the concept of meta-path, which is constructed based on direct neighbors and define composite semantic relations in heterogeneous graph. However, when the direct neighbor information is inadequate, which always happens due to insufficient observation, the quality of meta-paths cannot be guaranteed. Therefore, we propose a novel HGR framework based on latent direct neighbors. Specifically, random walks are first utilized to discover the potential candidates from indirect neighbors. Then HodgeRank is introduced to determine the latent direct neighbors according to their importance to the target. After that, neighborhood relationships are augmented with the selected latent direct neighbors, and the adjacency tensor of the heterogeneous graph is refactored correspondingly. Finally, Graph Transformer Network is adopted to construct semantic meta-paths automatically and generate HGR. Numerical experiments on different real-world heterogeneous networks show that our new approach can produce more meta-path instances and introduce more complex and diverse semantic information, and consequently achieves more accurate predictions compared with several state-of-the-art baselines.

Identification of MiRNA-Disease Associations Based on Information of Multi-Module and Meta-Path.

Cumulative research reveals that microRNAs (miRNAs) are involved in many critical biological processes including cell proliferation, differentiation and apoptosis. It is of great significance to figure out the associations between miRNAs and human diseases that are the basis for finding biomarkers for diagnosis and targets for treatment. To overcome the time-consuming and labor-intensive problems faced by traditional experiments, a computational method was developed to identify potential associations between miRNAs and diseases based on the graph attention network (GAT) with different meta-path mode and support vector (SVM). Firstly, we constructed a multi-module heterogeneous network based on the meta-path and learned the latent features of different modules by GAT. Secondly, we found the average of the latent features with weight to obtain a final node representation. Finally, we characterized miRNA-disease-association pairs with the node representation and trained an SVM to recognize potential associations. Based on the five-fold cross-validation and benchmark datasets, the proposed method achieved an area under the precision-recall curve (AUPR) of 0.9379 and an area under the receiver-operating characteristic curve (AUC) of 0.9472. The results demonstrate that our method has an outstanding practical application performance and can provide a reference for the discovery of new biomarkers and therapeutic targets.

A heterogeneous network-based method with attentive meta-path extraction for predicting drug-target interactions.

Predicting drug-target interactions (DTIs) is crucial at many phases of drug discovery and repositioning. Many computational methods based on heterogeneous networks (HNs) have proved their potential to predict DTIs by capturing extensive biological knowledge and semantic information from meta-paths. However, existing methods manually customize meta-paths, which is overly dependent on some specific expertise. Such strategy heavily limits the scalability and flexibility of these models, and even affects their predictive performance. To alleviate this limitation, we propose a novel HN-based method with attentive meta-path extraction for DTI prediction, named HampDTI, which is capable of automatically extracting useful meta-paths through a learnable attention mechanism instead of pre-definition based on domain knowledge. Specifically, by scoring multi-hop connections across various relations in the HN with each relation assigned an attention weight, HampDTI constructs a new trainable graph structure, called meta-path graph. Such meta-path graph implicitly measures the importance of every possible meta-path between drugs and targets. To enable HampDTI to extract more diverse meta-paths, we adopt a multi-channel mechanism to generate multiple meta-path graphs. Then, a graph neural network is deployed on the generated meta-path graphs to yield the multi-channel embeddings of drugs and targets. Finally, HampDTI fuses all embeddings from different channels for predicting DTIs. The meta-path graphs are optimized along with the model training such that HampDTI can adaptively extract valuable meta-paths for DTI prediction. The experiments on benchmark datasets not only show the superiority of HampDTI in DTI prediction over several baseline methods, but also, more importantly, demonstrate the effectiveness of the model discovering important meta-paths.

Fully connected autoencoder and convolutional neural network with attention-based method for inferring disease-related lncRNAs.

Since abnormal expression of long noncoding RNAs (lncRNAs) is often closely related to various human diseases, identification of disease-associated lncRNAs is helpful for exploring the complex pathogenesis. Most of recent methods concentrate on exploiting multiple kinds of data related to lncRNAs and diseases for predicting candidate disease-related lncRNAs. These methods, however, failed to deeply integrate the topology information from the meta-paths that are composed of lncRNA, disease and microRNA (miRNA) nodes. We proposed a new method based on fully connected autoencoders and convolutional neural networks, called ACLDA, for inferring potential disease-related lncRNA candidates. A heterogeneous graph that consists of lncRNA, disease and miRNA nodes were firstly constructed to integrate similarities, associations and interactions among them. Fully connected autoencoder-based module was established to extract the low-dimensional features of lncRNA, disease and miRNA nodes in the heterogeneous graph. We designed the attention mechanisms at the node feature level and at the meta-path level to learn more informative features and meta-paths. A module based on convolutional neural networks was constructed to encode the local topologies of lncRNA and disease nodes from multiple meta-path perspectives. The comprehensive experimental results demonstrated ACLDA achieves superior performance than several state-of-the-art prediction methods. Case studies on breast, lung and colon cancers demonstrated that ACLDA is able to discover the potential disease-related lncRNAs.