EMCMDA: predicting miRNA-disease associations via efficient matrix completion.

Abundant researches have consistently illustrated the crucial role of microRNAs (miRNAs) in a wide array of essential biological processes. Furthermore, miRNAs have been validated as promising therapeutic targets for addressing complex diseases. Given the costly and time-consuming nature of traditional biological experimental validation methods, it is imperative to develop computational methods. In the work, we developed a novel approach named efficient matrix completion (EMCMDA) for predicting miRNA-disease associations. First, we calculated the similarities across multiple sources for miRNA/disease pairs and combined this information to create a holistic miRNA/disease similarity measure. Second, we utilized this biological information to create a heterogeneous network and established a target matrix derived from this network. Lastly, we framed the miRNA-disease association prediction issue as a low-rank matrix-complete issue that was addressed via minimizing matrix truncated schatten p-norm. Notably, we improved the conventional singular value contraction algorithm through using a weighted singular value contraction technique. This technique dynamically adjusts the degree of contraction based on the significance of each singular value, ensuring that the physical meaning of these singular values is fully considered. We evaluated the performance of EMCMDA by applying two distinct cross-validation experiments on two diverse databases, and the outcomes were statistically significant. In addition, we executed comprehensive case studies on two prevalent human diseases, namely lung cancer and breast cancer. Following prediction and multiple validations, it was evident that EMCMDA proficiently forecasts previously undisclosed disease-related miRNAs. These results underscore the robustness and efficacy of EMCMDA in miRNA-disease association prediction.

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.

MHIF-MSEA: a novel model of miRNA set enrichment analysis based on multi-source heterogeneous information fusion.

Introduction: MicroRNAs (miRNAs) are a class of non-coding RNA molecules that play a crucial role in the regulation of diverse biological processes across various organisms. Despite not encoding proteins, miRNAs have been found to have significant implications in the onset and progression of complex human diseases. Methods: Conventional methods for miRNA functional enrichment analysis have certain limitations, and we proposed a novel method called MiRNA Set Enrichment Analysis based on Multi-source Heterogeneous Information Fusion (MHIF-MSEA). Three miRNA similarity networks (miRSN-DA, miRSN-GOA, and miRSN-PPI) were constructed in MHIF-MSEA. These networks were built based on miRNA-disease association, gene ontology (GO) annotation of target genes, and protein-protein interaction of target genes, respectively. These miRNA similarity networks were fused into a single similarity network with the averaging method. This fused network served as the input for the random walk with restart algorithm, which expanded the original miRNA list. Finally, MHIF-MSEA performed enrichment analysis on the expanded list. Results and Discussion: To determine the optimal network fusion approach, three case studies were introduced: colon cancer, breast cancer, and hepatocellular carcinoma. The experimental results revealed that the miRNA-miRNA association network constructed using miRSN-DA and miRSN-GOA exhibited superior performance as the input network. Furthermore, the MHIF-MSEA model performed enrichment analysis on differentially expressed miRNAs in breast cancer and hepatocellular carcinoma. The achieved p-values were 2.17e(-75) and 1.50e(-77), and the hit rates improved by 39.01% and 44.68% compared to traditional enrichment analysis methods, respectively. These results confirm that the MHIF-MSEA method enhances the identification of enriched miRNA sets by leveraging multiple sources of heterogeneous information, leading to improved insights into the functional implications of miRNAs in complex diseases.

HKFGCN: A novel multiple kernel fusion framework on graph convolutional network to predict microbe-drug associations.

Accumulating clinical studies have consistently demonstrated that the microbes in the human body closely interact with the human host, actively participating in the regulation of drug effectiveness. Identifying the associations between microbes and drugs can facilitate the development of drug discovery, and microbes have become a new target in antimicrobial drug development. However, the discovery of microbe-drug associations relies on clinical or biological experiments, which are not only time-consuming but also financially burdensome. Thus, the utilization of computational methods to predict microbe-drug associations holds promise for reducing costs and enhancing the efficiency of biological experiments. Here, we introduce a new computational method, called HKFGCN (Heterogeneous information Kernel Fusion Graph Convolution Network), to predict the microbe-drug associations. Instead of extracting feature from a single network in previous studies, HKFGCN separately extracts topological information features from different networks, and further refines them by generating Gaussian kernel features. HKFGCN consists of three main steps. Firstly, we constructed two similarity networks and a microbe-drug association network based on numerous biological data. Second, we employed two types of encoders to extract features from these networks. Next, Gaussian kernel features were obtained from the drug and microbe features at each layer. Finally, we reconstructed the bipartite microbe-drug graph based on the learned representations. Experimental results demonstrate the excellent performance of the HKFGCN model across different datasets using the cross-validation scheme. Additionally, we conduced case studies on human immunodeficiency virus, and the results were corroborated by existing literatures. The prediction model's code is available at https://github.com/roll-of-bubble/HKFGCN.

GSL-DTI: Graph structure learning network for Drug-Target interaction prediction.

MOTIVATION: Drug-target interaction prediction is an important area of research to predict whether there is an interaction between a drug molecule and its target protein. It plays a critical role in drug discovery and development by facilitating the identification of potential drug candidates and expediting the overall process. Given the time-consuming, expensive, and high-risk nature of traditional drug discovery methods, the prediction of drug-target interactions has become an indispensable tool. Using machine learning and deep learning to tackle this class of problems has become a mainstream approach, and graph-based models have recently received much attention in this field. However, many current graph-based Drug-Target Interaction (DTI) prediction methods rely on manually defined rules to construct the Drug-Protein Pair (DPP) network during the DPP representation learning process. However, these methods fail to capture the true underlying relationships between drug molecules and target proteins. RESULTS: We propose GSL-DTI, an automatic graph structure learning model used for predicting drug-target interactions (DTIs). Initially, we integrate large-scale heterogeneous networks using a graph convolution network based on meta-paths, effectively learning the representations of drugs and target proteins. Subsequently, we construct drug-protein pairs based on these representations. In contrast to previous studies that construct DPP networks based on manual rules, our method introduces an automatic graph structure learning approach. This approach utilizes a filter gate on the affinity scores of DPPs and relies on the classification loss of downstream tasks to guide the learning of the underlying DPP network structure. Based on the learned DPP network, we transform the prediction of drug-target interactions into a node classification problem. The comprehensive experiments conducted on three public datasets have shown the superiority of GSL-DTI in the tasks of DTI prediction. Additionally, GSL-DTI provides a fresh perspective for advancing research in graph structure learning for DTI prediction.

Inference of Gene Regulatory Networks Based on Multi-view Hierarchical Hypergraphs.

Since gene regulation is a complex process in which multiple genes act simultaneously, accurately inferring gene regulatory networks (GRNs) is a long-standing challenge in systems biology. Although graph neural networks can formally describe intricate gene expression mechanisms, current GRN inference methods based on graph learning regard only transcription factor (TF)-target gene interactions as pairwise relationships, and cannot model the many-to-many high-order regulatory patterns that prevail among genes. Moreover, these methods often rely on limited prior regulatory knowledge, ignoring the structural information of GRNs in gene expression profiles. Therefore, we propose a multi-view hierarchical hypergraphs GRN (MHHGRN) inference model. Specifically, multiple heterogeneous biological information is integrated to construct multi-view hierarchical hypergraphs of TFs and target genes, using hypergraph convolution networks to model higher order complex regulatory relationships. Meanwhile, the coupled information diffusion mechanism and the cross-domain messaging mechanism facilitate the information sharing between genes to optimise gene embedding representations. Finally, a unique channel attention mechanism is used to adaptively learn feature representations from multiple views for GRN inference. Experimental results show that MHHGRN achieves better results than the baseline methods on the E. coli and S. cerevisiae benchmark datasets of the DREAM5 challenge, and it has excellent cross-species generalization, achieving comparable or better performance on scRNA-seq datasets from five mouse and two human cell lines.

MECCH: Metapath Context Convolution-based Heterogeneous Graph Neural Networks.

Heterogeneous graph neural networks (HGNNs) were proposed for representation learning on structural data with multiple types of nodes and edges. To deal with the performance degradation issue when HGNNs become deep, researchers combine metapaths into HGNNs to associate nodes closely related in semantics but far apart in the graph. However, existing metapath-based models suffer from either information loss or high computation costs. To address these problems, we present a novel Metapath Context Convolution-based Heterogeneous Graph Neural Network (MECCH). MECCH leverages metapath contexts, a new kind of graph structure that facilitates lossless node information aggregation while avoiding any redundancy. Specifically, MECCH applies three novel components after feature preprocessing to extract comprehensive information from the input graph efficiently: (1) metapath context construction, (2) metapath context encoder, and (3) convolutional metapath fusion. Experiments on five real-world heterogeneous graph datasets for node classification and link prediction show that MECCH achieves superior prediction accuracy compared with state-of-the-art baselines with improved computational efficiency. The code is available at https://github.com/cynricfu/MECCH.

Health-aware food recommendation system with dual attention in heterogeneous graphs.

Recommender systems (RS) have been increasingly applied to food and health. However, challenges still remain, including the effective incorporation of heterogeneous information and the discovery of meaningful relationships among entities in the context of food and health recommendations. To address these challenges, we propose a novel framework, the Health-aware Food Recommendation System with Dual Attention in Heterogeneous Graphs (HFRS-DA), for unsupervised representation learning on heterogeneous graph-structured data. HFRS-DA utilizes an attention technique to reconstruct node features and edges and employs a dual hierarchical attention mechanism for enhanced unsupervised learning of attributed graph representations. HFRS-DA addresses the challenge of effectively leveraging the heterogeneous information in the graph and discovering meaningful semantic relationships between entities. The framework analyses recipe components and their neighbours in the heterogeneous graph and can discover popular and healthy recipes, thereby promoting healthy eating habits. We compare HFRS-DA using the Allrecipes dataset and find that it outperforms all the related methods from the literature. Our study demonstrates that HFRS-DA enhances the unsupervised learning of attributed graph representations, which is important in scenarios where labelled data is scarce or unavailable. HFRS-DA can generate node embeddings for unused data effectively, enabling both inductive and transductive learning.

Recommendation model based on intention decomposition and heterogeneous information fusion.

In order to solve the problem of timeliness of user and item interaction intention and the noise caused by heterogeneous information fusion, a recommendation model based on intention decomposition and heterogeneous information fusion (IDHIF) is proposed. First, the intention of the recently interacting items and the users of the recently interacting candidate items is decomposed, and the short feature representation of users and items is mined through long-short term memory and attention mechanism. Then, based on the method of heterogeneous information fusion, the interactive features of users and items are mined on the user-item interaction graph, the social features of users are mined on the social graph, and the content features of the item are mined on the knowledge graph. Different feature vectors are projected into the same feature space through heterogeneous information fusion, and the long feature representation of users and items is obtained through splicing and multi-layer perceptron. The final representation of users and items is obtained by combining short feature representation and long feature representation. Compared with the baseline model, the AUC on the Last.FM and Movielens-1M datasets increased by 1.83 and 4.03 percentage points, respectively, the F1 increased by 1.28 and 1.58 percentage points, and the Recall@20 increased by 3.96 and 2.90 percentage points. The model proposed in this paper can better model the features of users and items, thus enriching the vector representation of users and items, and improving the recommendation efficiency.

Drug-disease association prediction using semantic graph and function similarity representation learning over heterogeneous information networks.

Discovering new indications for existing drugs is a promising development strategy at various stages of drug research and development. However, most of them complete their tasks by constructing a variety of heterogeneous networks without considering available higher-order connectivity patterns in heterogeneous biological information networks, which are believed to be useful for improving the accuracy of new drug discovering. To this end, we propose a computational-based model, called SFRLDDA, for drug-disease association prediction by using semantic graph and function similarity representation learning. Specifically, SFRLDDA first integrates a heterogeneous information network (HIN) by drug-disease, drug-protein, protein-disease associations, and their biological knowledge. Second, different representation learning strategies are applied to obtain the feature representations of drugs and diseases from different perspectives over semantic graph and function similarity graphs constructed, respectively. At last, a Random Forest classifier is incorporated by SFRLDDA to discover potential drug-disease associations (DDAs). Experimental results demonstrate that SFRLDDA yields a best performance when compared with other state-of-the-art models on three benchmark datasets. Moreover, case studies also indicate that the simultaneous consideration of semantic graph and function similarity of drugs and diseases in the HIN allows SFRLDDA to precisely predict DDAs in a more comprehensive manner.

Cross-view contrastive representation learning approach to predicting DTIs via integrating multi-source information.

Drug-target interaction (DTI) prediction serves as the foundation of new drug findings and drug repositioning. For drugs/targets, the sequence data contains the biological structural information, while the heterogeneous network contains the biochemical functional information. These two types of information describe different aspects of drugs and targets. Due to the complexity of DTI machinery, it is necessary to learn the representation from multiple perspectives. We hereby try to design a way to leverage information from multi-source data to the maximum extent and find a strategy to fuse them. To address the above challenges, we propose a model, named MOVE (short for integrating multi-source information for predicting DTI via cross-view contrastive learning), for learning comprehensive representations of each drug and target from multi-source data. MOVE extracts information from the sequence view and the network view, then utilizes a fusion module with auxiliary contrastive learning to facilitate the fusion of representations. Experimental results on the benchmark dataset demonstrate that MOVE is effective in DTI prediction.

HeteEdgeWalk: A Heterogeneous Edge Memory Random Walk for Heterogeneous Information Network Embedding.

Most Heterogeneous Information Network (HIN) embedding methods use meta-paths to guide random walks to sample from HIN and perform representation learning in order to overcome the bias of traditional random walks that are more biased towards high-order nodes. Their performance depends on the suitability of the generated meta-paths for the current HIN. The definition of meta-paths requires domain expertise, which makes the results overly dependent on the meta-paths. Moreover, it is difficult to represent the structure of complex HIN with a single meta-path. In a meta-path guided random walk, some of the heterogeneous structures (e.g., node type(s)) are not among the node types specified by the meta-path, making this heterogeneous information ignored. In this paper, HeteEdgeWalk, a solution method that does not involve meta-paths, is proposed. We design a dynamically adjusted bidirectional edge-sampling walk strategy. Specifically, edge sampling and the storage of recently selected edge types are used to better sample the network structure in a more balanced and comprehensive way. Finally, node classification and clustering experiments are performed on four real HINs with in-depth analysis. The results show a maximum performance improvement of 2% in node classification and at least 0.6% in clustering compared to baselines. This demonstrates the superiority of the method to effectively capture semantic information from HINs.

An effective multi-task learning framework for drug repurposing based on graph representation learning.

Drug repurposing, which typically applies the procedure of drug-disease associations (DDAs) prediction, is a feasible solution to drug discovery. Compared with traditional methods, drug repurposing can reduce the cost and time for drug development and advance the success rate of drug discovery. Although many methods for drug repurposing have been proposed and the obtained results are relatively acceptable, there is still some room for improving the predictive performance, since those methods fail to consider fully the issue of sparseness in known drug-disease associations. In this paper, we propose a novel multi-task learning framework based on graph representation learning to identify DDAs for drug repurposing. In our proposed framework, a heterogeneous information network is first constructed by combining multiple biological datasets. Then, a module consisting of multiple layers of graph convolutional networks is utilized to learn low-dimensional representations of nodes in the constructed heterogeneous information network. Finally, two types of auxiliary tasks are designed to help to train the target task of DDAs prediction in the multi-task learning framework. Comprehensive experiments are conducted on real data and the results demonstrate the effectiveness of the proposed method for drug repurposing.

A lncRNA-disease association prediction tool development based on bridge heterogeneous information network via graph representation learning for family medicine and primary care.

Identification of long non-coding RNAs (lncRNAs) associated with common diseases is crucial for patient self-diagnosis and monitoring of health conditions using artificial intelligence (AI) technology at home. LncRNAs have gained significant attention due to their crucial roles in the pathogenesis of complex human diseases and identifying their associations with diseases can aid in developing diagnostic biomarkers at the molecular level. Computational methods for predicting lncRNA-disease associations (LDAs) have become necessary due to the time-consuming and labor-intensive nature of wet biological experiments in hospitals, enabling patients to access LDAs through their AI terminal devices at any time. Here, we have developed a predictive tool, LDAGRL, for identifying potential LDAs using a bridge heterogeneous information network (BHnet) constructed via Structural Deep Network Embedding (SDNE). The BHnet consists of three types of molecules as bridge nodes to implicitly link the lncRNA with disease nodes and the SDNE is used to learn high-quality node representations and make LDA predictions in a unified graph space. To assess the feasibility and performance of LDAGRL, extensive experiments, including 5-fold cross-validation, comparison with state-of-the-art methods, comparison on different classifiers and comparison of different node feature combinations, were conducted, and the results showed that LDAGRL achieved satisfactory prediction performance, indicating its potential as an effective LDAs prediction tool for family medicine and primary care.

LM-DTI: a tool of predicting drug-target interactions using the node2vec and network path score methods.

Introduction: Drug-target interaction (DTI) prediction is a key step in drug function discovery and repositioning. The emergence of large-scale heterogeneous biological networks provides an opportunity to identify drug-related target genes, which led to the development of several computational methods for DTI prediction. Methods: Considering the limitations of conventional computational methods, a novel tool named LM-DTI based on integrated information related to lncRNAs and miRNAs was proposed, which adopted the graph embedding (node2vec) and the network path score methods. First, LM-DTI innovatively constructed a heterogeneous information network containing eight networks composed of four types of nodes (drug, target, lncRNA, and miRNA). Next, the node2vec method was used to obtain feature vectors of drug as well as target nodes, and the path score vector of each drug-target pair was calculated using the DASPfind method. Finally, the feature vectors and path score vectors were merged and input into the XGBoost classifier to predict potential drug-target interactions. Results and Discussion: The 10-fold cross validations evaluate the classification accuracies of the LM-DTI. The prediction performance of LM-DTI in AUPR reached 0.96, which showed a significant improvement compared with those of conventional tools. The validity of LM-DTI has also been verified by manually searching literature and various databases. LM-DTI is scalable and computing efficient; thus representing a powerful drug relocation tool that can be accessed for free at http://www.lirmed.com:5038/lm_dti.

MNNMDA: Predicting human microbe-disease association via a method to minimize matrix nuclear norm.

Identifying the potential associations between microbes and diseases is the first step for revealing the pathological mechanisms of microbe-associated diseases. However, traditional culture-based microbial experiments are expensive and time-consuming. Thus, it is critical to prioritize disease-associated microbes by computational methods for further experimental validation. In this study, we proposed a novel method called MNNMDA, to predict microbe-disease associations (MDAs) by applying a Matrix Nuclear Norm method into known microbe and disease data. Specifically, we first calculated Gaussian interaction profile kernel similarity and functional similarity for diseases and microbes. Then we constructed a heterogeneous information network by combining the integrated disease similarity network, the integrated microbe similarity network and the known microbe-disease bipartite network. Finally, we formulated the microbe-disease association prediction problem as a low-rank matrix completion problem, which was solved by minimizing the nuclear norm of a matrix with a few regularization terms. We tested the performances of MNNMDA in three datasets including HMDAD, Disbiome, and Combined Data with small, medium and large sizes respectively. We also compared MNNMDA with 5 state-of-the-art methods including KATZHMDA, LRLSHMDA, NTSHMDA, GATMDA, and KGNMDA, respectively. MNNMDA achieved area under the ROC curves (AUROC) of 0.9536 and 0.9364 respectively on HDMAD and Disbiome, better than the AUCs of compared methods under the 5-fold cross-validation for all microbe-disease associations. It also obtained a relatively good performance with AUROC 0.8858 in the combined data. In addition, MNNMDA was also better than other methods in area under precision and recall curve (AUPR) under the 5-fold cross-validation for all associations, and in both AUROC and AUPR under the 5-fold cross-validation for diseases and the 5-fold cross-validation for microbes. Finally, the case studies on colon cancer and inflammatory bowel disease (IBD) also validated the effectiveness of MNNMDA. In conclusion, MNNMDA is an effective method in predicting microbe-disease associations. Availability: The codes and data for this paper are freely available at Github https://github.com/Haiyan-Liu666/MNNMDA.

LPIH2V: LncRNA-protein interactions prediction using HIN2Vec based on heterogeneous networks model.

LncRNA-protein interaction plays an important role in the development and treatment of many human diseases. As the experimental approaches to determine lncRNA-protein interactions are expensive and time-consuming, considering that there are few calculation methods, therefore, it is urgent to develop efficient and accurate methods to predict lncRNA-protein interactions. In this work, a model for heterogeneous network embedding based on meta-path, namely LPIH2V, is proposed. The heterogeneous network is composed of lncRNA similarity networks, protein similarity networks, and known lncRNA-protein interaction networks. The behavioral features are extracted in a heterogeneous network using the HIN2Vec method of network embedding. The results showed that LPIH2V obtains an AUC of 0.97 and ACC of 0.95 in the 5-fold cross-validation test. The model successfully showed superiority and good generalization ability. Compared to other models, LPIH2V not only extracts attribute characteristics by similarity, but also acquires behavior properties by meta-path wandering in heterogeneous networks. LPIH2V would be beneficial in forecasting interactions between lncRNA and protein.

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-HGT: Metapath-aware HyperGraph Transformer for heterogeneous information network embedding.

Heterogeneous information network embedding aims to learn low-dimensional node vectors in heterogeneous information networks (HINs), concerning not only structural information but also heterogeneity of diverse node and relation types. Most existing HIN embedding models mainly rely on metapath to define composite relations between node pairs and thus extract substructures from the original HIN. However, due to the pairwise structure of metapath, these models fail to capture the high-order relations (such as "Multiple authors co-authoring a paper") implicitly contained in HINs. To tackle the limitation, this paper proposes a Metapath-aware HyperGraph Transformer (Meta-HGT) for node embedding in HINs. Meta-HGT first extends metapath to guide the high-order relation extraction from original HIN and constructs multiple metapath based hypergraphs with diverse composite semantics. Then, Meta-HGT learns the latent node and hyperedge embeddings in each metapath based hypergraph through Meta-HGT layers. Each layer consists of two types of components, i.e., intra-hyperedge aggregation and inter-hyperedge aggregation, in which a novel type-dependent attention mechanism is proposed for node and hyperedge feature aggregation. Finally, it fuses multiple node embeddings learned from different metapath based hypergraphs via a semantic attention layer and generates the final node embeddings. Extensive experiments have been conducted on three HIN benchmarks for node classification. The results demonstrate that Meta-HGT achieves state-of-the-art performance on all three datasets.

Investigation on Mechanisms of Osteoking Against Four Types of Bone Injury Diseases Based on Heterogeneous Information Network with Concept of "Treating Different Diseases with an Identical Treatment" / 中国实验方剂学杂志

ObjectiveTo elucidate the mechanism of Osteoking against fracture， femoral head necrosis， osteoarthritis， and lumbar disc herniation by integrating heterogeneous information network mining and experimental validation. MethodOn the basis of the disease-related database and transcriptome expression profiling dataset， as well as the ETCM database， the gene sets related to four target diseases and the candidate target spectrum of Osteoking were obtained through the integration and analysis of bioinformatics data， and a "disease-syndrome-formula-target-pathway-effect" heterogeneous information network was constructed. In addition， by functional enrichment analysis， the core targets of Osteoking in interfering with the imbalance network of four kinds of bone injury diseases， the biological pathways involved， and the corresponding clinical symptoms were screened， and they were verified in animal experiments. ResultHeterogeneous information network mining indicates that Osteoking may commonly reverse the imbalance networks of fracture， femoral head necrosis， osteoarthritis， and lumbar disc herniation via regulating cell function and activity， inhibiting inflammatory response， reducing bone destruction， and improving the immune function of the body by modulating relevant core candidate targets such as RAC-alpha serine/threonine-protein kinase （Akt1）， catenin beta-1 （CTNNB1）， epidermal growth factor receptor （EGFR）， heat shock protein 90-alpha （HSP90AA1）， and phosphatidylinositol 3-kinase catalytic subunit alpha isoform （PI3KCA）， as well as related biological pathways such as phosphatidylinositide 3-kinases/protein kinase B （PI3K/Akt）， janus kinase/signal transducer and activator of transcription （JAK/STAT）， tumor necrosis factor （TNF）， nuclear factor kappa-B （NF-κB）， and Toll-like receptors. In particular， Osteoking may improve the blood supply of the fracture end by regulating blood circulation at the target site of the disease， and it may maintain the balance of bone metabolism by regulating hormone-related pathways to promote fracture healing. In addition， Osteoking may relieve lipid metabolism disorders by targeting and regulating lipid-related pathways， accelerate bone formation and bone repair， and delay the progression of femoral head necrosis. Osteoking may relieve the symptoms of pain by acting on neurological pathways to reduce local nociceptive stimulation in patients with osteoarthritis and lumbar disc herniation. Further experimental validation demonstrates that the PI3K/Akt signaling pathway is the most significantly enriched pathway for the key network targets of Osteoking for the four diseases. The candidate target of Osteoking may have the strongest association with the network of fracture-related genes. Therefore， this study chooses fracture as the target disease to verify the efficacy of Osteoking. The results show that Osteoking can accelerate bone formation and promote fracture healing by inhibiting the activation of the PI3K/Akt signaling axis. ConclusionThe study shows that the main mechanism of "treating different diseases with an identical treatment" of four bone injury diseases with Osteoking involves cell function regulation and immune inflammation-related signaling pathways. Further experimental validation identifies that the PI3K/Akt signaling axis may be one of the key pathways of Osteoking to promote bone regeneration， bone reconstruction， and bone metabolism homeostasis.