Drug-target interaction prediction through fine-grained selection and bidirectional random walk methodology.

The study of drug-target interaction plays an important role in the process of drug development. The subject of DTI forecasting has advanced significantly in the last several years, yielding numerous significant research findings and methodologies. Heterogeneous data sources provide richer information and comprehensive perspectives for drug-target interaction prediction, so many existing methods rely on heterogeneous networks, and graph embedding technology becomes an important technology to extract information from heterogeneous networks. These approaches, however, are less concerned with potential noisy information in heterogeneous networks and more focused on the extent of information extraction in those networks. Based on this, a potential DTI predictive network model called FBRWPC is proposed in this paper. It uses a fine-grained similarity selection program to first integrate similarity on similar networks and then a bidirectional random walk graph embedding learning method with restart to obtain an updated drug target interaction matrix. Through the use of similarity selection and fine-grained selection similarity integration, the framework can effectively filter out the noise present in heterogeneous networks and enhance the model's prediction performance. The experimental findings demonstrate that, even after being split up into four distinct types of data sets, FBRWPC can still retain great prediction performance, a sign of the model's resilience and good generalization.

Predicting Disease-Metabolite Associations Based on the Metapath Aggregation of Tripartite Heterogeneous Networks.

The exploration of the interactions between diseases and metabolites holds significant implications for the diagnosis and treatment of diseases. However, traditional experimental methods are time-consuming and costly, and current computational methods often overlook the influence of other biological entities on both. In light of these limitations, we proposed a novel deep learning model based on metapath aggregation of tripartite heterogeneous networks (MAHN) to explore disease-related metabolites. Specifically, we introduced microbes to construct a tripartite heterogeneous network and employed graph convolutional network and enhanced GraphSAGE to learn node features with metapath length 3. Additionally, we utilized node-level and semantic-level attention mechanisms, a more granular approach, to aggregate node features with metapath length 2. Finally, the reconstructed association probability is obtained by fusing features from different metapaths into the bilinear decoder. The experiments demonstrate that the proposed MAHN model achieved superior performance in five-fold cross-validation with Acc (91.85%), Pre (90.48%), Recall (93.53%), F1 (91.94%), AUC (97.39%), and AUPR (97.47%), outperforming four state-of-the-art algorithms. Case studies on two complex diseases, irritable bowel syndrome and obesity, further validate the predictive results, and the MAHN model is a trustworthy prediction tool for discovering potential metabolites. Moreover, deep learning models integrating multi-omics data represent the future mainstream direction for predicting disease-related biological entities.

Three-layer heterogeneous network based on the integration of CircRNA information for MiRNA-disease association prediction.

Increasing research has shown that the abnormal expression of microRNA (miRNA) is associated with many complex diseases. However, biological experiments have many limitations in identifying the potential disease-miRNA associations. Therefore, we developed a computational model of Three-Layer Heterogeneous Network based on the Integration of CircRNA information for MiRNA-Disease Association prediction (TLHNICMDA). In the model, a disease-miRNA-circRNA heterogeneous network is built by known disease-miRNA associations, known miRNA-circRNA interactions, disease similarity, miRNA similarity, and circRNA similarity. Then, the potential disease-miRNA associations are identified by an update algorithm based on the global network. Finally, based on global and local leave-one-out cross validation (LOOCV), the values of AUCs in TLHNICMDA are 0.8795 and 0.7774. Moreover, the mean and standard deviation of AUC in 5-fold cross-validations is 0.8777+/-0.0010. Especially, the two types of case studies illustrated the usefulness of TLHNICMDA in predicting disease-miRNA interactions.

A hybrid PSO-GWO-based phase shift design for a hybrid-RIS-aided heterogeneous network system.

The effectiveness of developing reconfigurable intelligent surfaces (RIS) for heterogeneous network (HetNet) systems has resulted in significant spectral efficiency (SE) gains. The majority of current research has not addressed effectively whether a hybrid metaheuristic technique may be used to create the hybrid RIS phase changes in HetNet. In this paper, we study a heterogeneous network (HetNet) assisted by a hybrid reconfigurable intelligent surface (H-RIS). Compared with the passive RIS, a hybrid RIS that has only 8% active elements is proposed to enhance by reflecting and amplifying incident signals. Hybrid RIS phase shift and SBS transmit beamforming are optimised. At the SBS, transmit beamforming based on zero-forcing is employed, whereas for hybrid RIS phase shift optimisation, the hybrid PSO-GWO (HPSOGWO) method is employed. The exploitation power of particle swarm optimisation (PSO) and the exploration power of the grey wolf optimizer (GWO) are combined in this hybrid approach. Simulation findings show that the suggested method, which uses only modest active RIS elements, can achieve a significant spectral efficiency improvement over both RIS-aided HetNet with totally passive RIS elements but with the SDR method to optimise the RIS phase changes and RIS-aided HetNet with entirely active RIS elements but with the Lagrange multiplier (LM) scheme to design the phase shift at the active RIS.

Spatiotemporal constrained RNA-protein heterogeneous network for protein complex identification.

The identification of protein complexes from protein interaction networks is crucial in the understanding of protein function, cellular processes and disease mechanisms. Existing methods commonly rely on the assumption that protein interaction networks are highly reliable, yet in reality, there is considerable noise in the data. In addition, these methods fail to account for the regulatory roles of biomolecules during the formation of protein complexes, which is crucial for understanding the generation of protein interactions. To this end, we propose a SpatioTemporal constrained RNA-protein heterogeneous network for Protein Complex Identification (STRPCI). STRPCI first constructs a multiplex heterogeneous protein information network to capture deep semantic information by extracting spatiotemporal interaction patterns. Then, it utilizes a dual-view aggregator to aggregate heterogeneous neighbor information from different layers. Finally, through contrastive learning, STRPCI collaboratively optimizes the protein embedding representations under different spatiotemporal interaction patterns. Based on the protein embedding similarity, STRPCI reweights the protein interaction network and identifies protein complexes with core-attachment strategy. By considering the spatiotemporal constraints and biomolecular regulatory factors of protein interactions, STRPCI measures the tightness of interactions, thus mitigating the impact of noisy data on complex identification. Evaluation results on four real PPI networks demonstrate the effectiveness and strong biological significance of STRPCI. The source code implementation of STRPCI is available from https://github.com/LI-jasm/STRPCI.

AE-RW: Predicting miRNA-disease associations by using autoencoder and random walk on miRNA-gene-disease heterogeneous network.

Since scientific investigations have demonstrated that aberrant expression of miRNAs brings about the incidence of numerous intricate diseases, precise determination of miRNA-disease relationships greatly contributes to the advancement of human medical progress. To tackle the issue of inefficient conventional experimental approaches, numerous computational methods have been proposed to predict miRNA-disease association with enhanced accuracy. However, constructing miRNA-gene-disease heterogeneous network by incorporating gene information has been relatively under-explored in existing computational techniques. Accordingly, this paper puts forward a technique to predict miRNA-disease association by applying autoencoder and implementing random walk on miRNA-gene-disease heterogeneous network(AE-RW). Firstly, we integrate association information and similarities between miRNAs, genes, and diseases to construct a miRNA-gene-disease heterogeneous network. Subsequently, we consolidate two network feature representations extracted independently via an autoencoder and a random walk procedure. Finally, deep neural network(DNN) are utilized to conduct association prediction. The experimental results demonstrate that the AE-RW model achieved an AUC of 0.9478 through 5-fold CV on the HMDD v3.2 dataset, outperforming the five most advanced existing models. Additionally, case studies were implemented for breast and lung cancer, further validated the superior predictive capabilities of our model.

Tissue specific tumor-gene link prediction through sampling based GNN using a heterogeneous network.

A tissue sample is a valuable resource for understanding a patient's symptoms and health status in relation to tumor growth. Recent research seeks to establish a connection between tissue-specific tumor samples and genetic markers (genes). This breakthrough has paved the way for personalized cancer therapies. With this motivation, the proposed model constructs a heterogeneous network based on tumor sample-gene relation data and gene-gene interaction data. This network also incorporates tissue-specific gene expression and primary site-based gene counts as features, enabling tissue-specific predictions. Graph neural networks (GNNs) have proven effective in modeling complex interactions and predicting links within this network. The proposed model has successfully predicted tumor-gene associations by leveraging sampling-based GNNs and link layer embedding. The model's performance metrics, such as AUC-ROC scores, reached approximately 94%, demonstrating the potential of this heterogeneous network in predicting tissue-specific tumor sample-gene links. This paper's findings highlight the importance of tissue-specific associations in cancer research.

PUTransGCN: identification of piRNA-disease associations based on attention encoding graph convolutional network and positive unlabelled learning.

Piwi-interacting RNAs (piRNAs) play a crucial role in various biological processes and are implicated in disease. Consequently, there is an escalating demand for computational tools to predict piRNA-disease interactions. Although there have been computational methods proposed for the detection of piRNA-disease associations, the problem of imbalanced and sparse dataset has brought great challenges to capture the complex relationships between piRNAs and diseases. In response to this necessity, we have developed a novel computational architecture, denoted as PUTransGCN, which uses heterogeneous graph convolutional networks to uncover potential piRNA-disease associations. Additionally, the attention mechanism was used to adjust the weight parameters of aggregation heterogeneous node features automatically. For tackling the imbalanced dataset problem, the combined positive unlabelled learning (PUL) method comprising PU bagging, two-step and spy technique was applied to select reliable negative associations. The features of piRNAs and diseases were derived from three distinct biological sources by PUTransGCN, including information on piRNA sequences, semantic terms related to diseases and the existing network of piRNA-disease associations. In the experiment, PUTransGCN performs in 5-fold cross-validation with an AUC of 0.93 and 0.95 on two datasets, respectively, which outperforms the other six state-of-the-art models. We compared three different PUL methods, and the results of the ablation experiment indicate that the combined PUL method yields the best results. The PUTransGCN could serve as a valuable piRNA-disease prediction tool for upcoming studies in the biomedical field. The code for PUTransGCN is available at https://github.com/chenqiuhao/PUTransGCN.

AMPFLDAP: Adaptive Message Passing and Feature Fusion on Heterogeneous Network for LncRNA-Disease Associations Prediction.

Exploration of the intricate connections between long noncoding RNA (lncRNA) and diseases, referred to as lncRNA-disease associations (LDAs), plays a pivotal and indispensable role in unraveling the underlying molecular mechanisms of diseases and devising practical treatment approaches. It is imperative to employ computational methods for predicting lncRNA-disease associations to circumvent the need for superfluous experimental endeavors. Graph-based learning models have gained substantial popularity in predicting these associations, primarily because of their capacity to leverage node attributes and relationships within the network. Nevertheless, there remains much room for enhancing the performance of these techniques by incorporating and harmonizing the node attributes more effectively. In this context, we introduce a novel model, i.e., Adaptive Message Passing and Feature Fusion (AMPFLDAP), for forecasting lncRNA-disease associations within a heterogeneous network. Firstly, we constructed a heterogeneous network involving lncRNA, microRNA (miRNA), and diseases based on established associations and employing Gaussian interaction profile kernel similarity as a measure. Then, an adaptive topological message passing mechanism is suggested to address the information aggregation for heterogeneous networks. The topological features of nodes in the heterogeneous network were extracted based on the adaptive topological message passing mechanism. Moreover, an attention mechanism is applied to integrate both topological and semantic information to achieve the multimodal features of biomolecules, which are further used to predict potential LDAs. The experimental results demonstrated that the performance of the proposed AMPFLDAP is superior to seven state-of-the-art methods. Furthermore, to validate its efficacy in practical scenarios, we conducted detailed case studies involving three distinct diseases, which conclusively demonstrated AMPFLDAP's effectiveness in the prediction of LDAs.

NGCN: Drug-target interaction prediction by integrating information and feature learning from heterogeneous network.

Drug-target interaction (DTI) prediction is essential for new drug design and development. Constructing heterogeneous network based on diverse information about drugs, proteins and diseases provides new opportunities for DTI prediction. However, the inherent complexity, high dimensionality and noise of such a network prevent us from taking full advantage of these network characteristics. This article proposes a novel method, NGCN, to predict drug-target interactions from an integrated heterogeneous network, from which to extract relevant biological properties and association information while maintaining the topology information. It focuses on learning the topology representation of drugs and targets to improve the performance of DTI prediction. Unlike traditional methods, it focuses on learning the low-dimensional topology representation of drugs and targets via graph-based convolutional neural network. NGCN achieves substantial performance improvements over other state-of-the-art methods, such as a nearly 1.0% increase in AUPR value. Moreover, we verify the robustness of NGCN through benchmark tests, and the experimental results demonstrate it is an extensible framework capable of combining heterogeneous information for DTI prediction.

MFA-DTI: Drug-target interaction prediction based on multi-feature fusion adopted framework.

The identification of drug-target interactions (DTI) is a valuable step in the drug discovery and repositioning process. However, traditional laboratory experiments are time-consuming and expensive. Computational methods have streamlined research to determine DTIs. The application of deep learning methods has significantly improved the prediction performance for DTIs. Modern deep learning methods can leverage multiple sources of information, including sequence data that contains biological structural information, and interaction data. While useful, these methods cannot be effectively applied to each type of information individually (e.g., chemical structure and interaction network) and do not take into account the specificity of DTI data such as low- or zero-interaction biological entities. To overcome these limitations, we propose a method called MFA-DTI (Multi-feature Fusion Adopted framework for DTI). MFA-DTI consists of three modules: an interaction graph learning module that processes the interaction network to generate interaction vectors, a chemical structure learning module that extracts features from the chemical structure, and a fusion module that combines these features for the final prediction. To validate the performance of MFA-DTI, we conducted experiments on six public datasets under different settings. The results indicate that the proposed method is highly effective in various settings and outperforms state-of-the-art methods.

SAGESDA: Multi-GraphSAGE networks for predicting SnoRNA-disease associations.

Over the years, extensive research has highlighted the functional roles of small nucleolar RNAs in various biological processes associated with the development of complex human diseases. Therefore, understanding the existing relationships between different snoRNAs and diseases is crucial for advancing disease diagnosis and treatment. However, classical biological experiments for identifying snoRNA-disease associations are expensive and time-consuming. Therefore, there is an urgent need for cost-effective computational techniques that can enhance the efficiency and accuracy of prediction. While several computational models have already been proposed, many suffer from limitations and suboptimal performance. In this study, we introduced a novel Graph Neural Network-based (GNN) classification model, called SAGESDA, which is implemented through the GraphSAGE architecture with attention for the prediction of snoRNA-disease associations. The classifier leverages local neighbouring nodes in a heterogeneous network to generate new node embeddings through message passing. The mini-batch gradient descent technique was applied to divide the graph into smaller sub-graphs, which enhances the model's accuracy, speed and scalability. With these advancements, SAGESDA attained an area under the receiver operating characteristic (ROC) curve (AUC) of 0.92 using the standard dot product classifier, surpassing previous related studies. This notable performance demonstrates that SAGESDA is a promising model for predicting unknown snoRNA-disease associations with high accuracy. The SAGESDA implementation details can be obtained from https://github.com/momanyibiffon/SAGESDA.git.

MHESMMR: a multilevel model for predicting the regulation of miRNAs expression by small molecules.

According to the expression of miRNA in pathological processes, miRNAs can be divided into oncogenes or tumor suppressors. Prediction of the regulation relations between miRNAs and small molecules (SMs) becomes a vital goal for miRNA-target therapy. But traditional biological approaches are laborious and expensive. Thus, there is an urgent need to develop a computational model. In this study, we proposed a computational model to predict whether the regulatory relationship between miRNAs and SMs is up-regulated or down-regulated. Specifically, we first use the Large-scale Information Network Embedding (LINE) algorithm to construct the node features from the self-similarity networks, then use the General Attributed Multiplex Heterogeneous Network Embedding (GATNE) algorithm to extract the topological information from the attribute network, and finally utilize the Light Gradient Boosting Machine (LightGBM) algorithm to predict the regulatory relationship between miRNAs and SMs. In the fivefold cross-validation experiment, the average accuracies of the proposed model on the SM2miR dataset reached 79.59% and 80.37% for up-regulation pairs and down-regulation pairs, respectively. In addition, we compared our model with another published model. Moreover, in the case study for 5-FU, 7 of 10 candidate miRNAs are confirmed by related literature. Therefore, we believe that our model can promote the research of miRNA-targeted therapy.

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.

AMGDTI: drug-target interaction prediction based on adaptive meta-graph learning in heterogeneous network.

Prediction of drug-target interactions (DTIs) is essential in medicine field, since it benefits the identification of molecular structures potentially interacting with drugs and facilitates the discovery and reposition of drugs. Recently, much attention has been attracted to network representation learning to learn rich information from heterogeneous data. Although network representation learning algorithms have achieved success in predicting DTI, several manually designed meta-graphs limit the capability of extracting complex semantic information. To address the problem, we introduce an adaptive meta-graph-based method, termed AMGDTI, for DTI prediction. In the proposed AMGDTI, the semantic information is automatically aggregated from a heterogeneous network by training an adaptive meta-graph, thereby achieving efficient information integration without requiring domain knowledge. The effectiveness of the proposed AMGDTI is verified on two benchmark datasets. Experimental results demonstrate that the AMGDTI method overall outperforms eight state-of-the-art methods in predicting DTI and achieves the accurate identification of novel DTIs. It is also verified that the adaptive meta-graph exhibits flexibility and effectively captures complex fine-grained semantic information, enabling the learning of intricate heterogeneous network topology and the inference of potential drug-target relationship.

DapBCH: a disease association prediction model Based on Cross-species and Heterogeneous graph embedding.

The study of comorbidity can provide new insights into the pathogenesis of the disease and has important economic significance in the clinical evaluation of treatment difficulty, medical expenses, length of stay, and prognosis of the disease. In this paper, we propose a disease association prediction model DapBCH, which constructs a cross-species biological network and applies heterogeneous graph embedding to predict disease association. First, we combine the human disease-gene network, mouse gene-phenotype network, human-mouse homologous gene network, and human protein-protein interaction network to reconstruct a heterogeneous biological network. Second, we apply heterogeneous graph embedding based on meta-path aggregation to generate the feature vector of disease nodes. Finally, we employ link prediction to obtain the similarity of disease pairs. The experimental results indicate that our model is highly competitive in predicting the disease association and is promising for finding potential disease associations.

MDformer: A transformer-based method for predicting miRNA-Disease associations using multi-source feature fusion and maximal meta-path instances encoding.

There is a growing body of evidence suggesting that microRNAs (miRNAs), small biological molecules, play a crucial role in the diagnosis, treatment, and prognostic assessment of diseases. However, it is often inefficient to verify the association between miRNAs and diseases (MDA) through traditional experimental methods. Based on this situation, researchers have proposed various computational-based methods, but the existing methods often have many drawbacks in terms of predictive effectiveness and accuracy. Therefore, in order to improve the prediction performance of computational methods, we propose a transformer-based prediction model (MDformer) for multi-source feature information. Specifically, first, we consider multiple features of miRNAs and diseases from the molecular biology perspective and utilize them in a fusion. Then high-quality node feature embeddings were generated using a feature encoder based on the transformer architecture and meta-path instances. Finally, a deep neural network was built for MDA prediction. To evaluate the performance of our model, we performed multiple 5-fold cross-validations as well as comparison experiments on HMDD v3.2 and HMDD v2.0 databases, and the experimental results of the average ROC area under the curve (AUC) were higher than the comparative methods for both databases at 0.9506 and 0.9369. We conducted case studies on five highly lethal cancers (breast, lung, colorectal, gastric, and hepatocellular cancers), and the first 30 predictions for these five diseases achieved 97.3% accuracy. In conclusion, MDformer is a reliable and scientifically sound tool that can be used to accurately predict MDA. In addition, the source code is available at https://github.com/Linda908/MDformer.

HNetGO: protein function prediction via heterogeneous network transformer.

Protein function annotation is one of the most important research topics for revealing the essence of life at molecular level in the post-genome era. Current research shows that integrating multisource data can effectively improve the performance of protein function prediction models. However, the heavy reliance on complex feature engineering and model integration methods limits the development of existing methods. Besides, models based on deep learning only use labeled data in a certain dataset to extract sequence features, thus ignoring a large amount of existing unlabeled sequence data. Here, we propose an end-to-end protein function annotation model named HNetGO, which innovatively uses heterogeneous network to integrate protein sequence similarity and protein-protein interaction network information and combines the pretraining model to extract the semantic features of the protein sequence. In addition, we design an attention-based graph neural network model, which can effectively extract node-level features from heterogeneous networks and predict protein function by measuring the similarity between protein nodes and gene ontology term nodes. Comparative experiments on the human dataset show that HNetGO achieves state-of-the-art performance on cellular component and molecular function branches.

Cellular Network Fault Diagnosis Method Based on a Graph Convolutional Neural Network.

The efficient and accurate diagnosis of faults in cellular networks is crucial for ensuring smooth and uninterrupted communication services. In this paper, we propose an improved 4G/5G network fault diagnosis with a few effective labeled samples. Our solution is a heterogeneous wireless network fault diagnosis algorithm based on Graph Convolutional Neural Network (GCN). First, the common failure types of 4G/5G networks are analyzed, and then the graph structure is constructed with the data in the network parameter, given data sets as nodes and similarities as edges. GCN is used to extract features from the graph data, complete the classification task for nodes, and finally predict the fault types of cells. A large number of experiments are carried out based on the real data set, which is achieved by driving tests. The results show that, compared with a variety of traditional algorithms, the proposed method can effectively improve the performance of network fault diagnosis with a small number of labeled samples.

Heterogeneous graph framework for predicting the association between lncRNA and disease and case on uterine fibroid.

Long non-coding RNAs (lncRNAs) play crucial regulatory roles in various cellular processes, including gene expression, chromatin remodeling, and protein localization. Dysregulation of lncRNAs has been linked to several diseases, making it essential to understand their functions in disease mechanisms and therapeutic strategies. However, traditional experimental methods for studying lncRNA function are time-consuming, expensive, and offer limited insights. In recent years, computational methods have emerged as valuable tools for predicting lncRNA functions and their associations with diseases. However, many existing methods focus on constructing separate networks for lncRNA and disease similarity, resulting in information loss and insufficient processing capacity for isolated nodes. To address this, we developed 'RGLD' by combining Random Walk with restarting (RWR), Graph Neural Network (GNN), and Graph Attention Networks (GAT) to predict lncRNA-disease associations in a heterogeneous network. RGLD achieved an impressive AUC of 0.88, outperforming other methods. It can also predict novel associations between lncRNAs and diseases. RGLD identified HOTAIR, MEG3, and PVT1 as lncRNAs associated with uterine fibroids. Biological experiments directly or indirectly verified the involvement of these three lncRNAs in uterine fibroids, validating the accuracy of RGLD's predictions. Furthermore, we extensively discussed the functions of the target genes regulated by these lncRNAs in uterine fibroids, providing evidence for their role in the development and progression of the disease.