Heterogeneous Graph Inference Research Articles

Heterogeneous graph inference with range constrainted [formula omitted]-collaborative matrix factorization for small molecule-miRNA association prediction

MicroRNAs (miRNAs) play a vital role in regulating gene expression and various biological processes. As a result, they have been identified as effective targets for small molecule (SM) drugs in disease treatment. Heterogeneous graph inference stands as a classical approach for predicting SM-miRNA associations, showcasing commendable convergence accuracy and speed. However, most existing methods do not adequately address the inherent sparsity in SM-miRNA association networks, and imprecise SM/miRNA similarity metrics reduce the accuracy of predicting SM-miRNA associations. In this research, we proposed a heterogeneous graph inference with range constrained L2,1-collaborative matrix factorization (HGIRCLMF) method to predict potential SM-miRNA associations. First, we computed the multi-source similarities of SM/miRNA and integrated these similarity information into a comprehensive SM/miRNA similarity. This step improved the accuracy of SM and miRNA similarity, ensuring reliability for the subsequent inference of the heterogeneity map. Second, we used a range constrained L2,1-collaborative matrix factorization (RCLMF) model to pre-populate the SM-miRNA association matrix with missing values. In this step, we developed a novel matrix decomposition method that enhances the robustness and formative nature of SM-miRNA edges between SM networks and miRNA networks. Next, we built a well-established SM-miRNA heterogeneous network utilizing the processed biological information. Finally, HGIRCLMF used this network data to infer unknown association pair scores. We implemented four cross-validation experiments on two distinct datasets, and HGIRCLMF acquired the highest areas under the curve, surpassing six state-of-the-art computational approaches. Furthermore, we performed three case studies to validate the predictive power of our method in practical application.

Accurate Localization in LOS/NLOS Channel Coexistence Scenarios Based on Heterogeneous Knowledge Graph Inference

Accurate localization is one of the basic requirements for smart cities and smart factories. In wireless cellular network localization, the straight-line propagation of electromagnetic waves between base stations and users is called line-of-sight (LOS) wireless propagation. In some cases, electromagnetic wave signals cannot propagate in a straight line due to obstruction by buildings or trees, and these scenarios are usually called non-LOS (NLOS) wireless propagation. Traditional localization algorithms such as TDOA, AOA, etc. , are based on LOS channels, which are no longer applicable in environments where NLOS propagation is dominant, and in most scenarios, the number of base stations with LOS channels containing users is often small, resulting in traditional localization algorithms being unable to satisfy the accuracy demand of high-precision localization. In addition, some nonideal factors may be included in the actual system, all of which can lead to localization accuracy degradation. Therefore, the approach developed in this paper uses knowledge graph and graph neural network (GNN) technology to model communication data as knowledge graphs, and it adopts the knowledge graph inference technique based on a heterogeneous graph attention mechanism to infer unknown data representations in complex scenarios based on the known data and the relationships between the data to achieve high-precision localization in scenarios with LOS/NLOS channel coexistence. We experimentally demonstrate a spatial 2D localization accuracy level of approximately 10 meters on multiple datasets and find that our proposed algorithm has higher accuracy and stronger robustness than the state-of-the-art algorithms.

A new integrated framework for the identification of potential virus-drug associations.

With the increasingly serious problem of antiviral drug resistance, drug repurposing offers a time-efficient and cost-effective way to find potential therapeutic agents for disease. Computational models have the ability to quickly predict potential reusable drug candidates to treat diseases. In this study, two matrix decomposition-based methods, i.e., Matrix Decomposition with Heterogeneous Graph Inference (MDHGI) and Bounded Nuclear Norm Regularization (BNNR), were integrated to predict anti-viral drugs. Moreover, global leave-one-out cross-validation (LOOCV), local LOOCV, and 5-fold cross-validation were implemented to evaluate the performance of the proposed model based on datasets of DrugVirus that consist of 933 known associations between 175 drugs and 95 viruses. The results showed that the area under the receiver operating characteristics curve (AUC) of global LOOCV and local LOOCV are 0.9035 and 0.8786, respectively. The average AUC and the standard deviation of the 5-fold cross-validation for DrugVirus datasets are 0.8856 ± 0.0032. We further implemented cross-validation based on MDAD and aBiofilm, respectively, to evaluate the performance of the model. In particle, MDAD (aBiofilm) dataset contains 2,470 (2,884) known associations between 1,373 (1,470) drugs and 173 (140) microbes. In addition, two types of case studies were carried out further to verify the effectiveness of the model based on the DrugVirus and MDAD datasets. The results of the case studies supported the effectiveness of MHBVDA in identifying potential virus-drug associations as well as predicting potential drugs for new microbes.

Integrated multi-similarity fusion and heterogeneous graph inference for drug-target interaction prediction

Drug-target interaction (DTI) prediction performs a crucial part in drug discovery and design. Although many computational approaches for such prediction have been proposed, current researches still generally adopt chemical similarities of drugs or the sequence similarities of targets. However, the valuable information of known interactions has not been noticed, and the existing noise and useless information reduce the accuracy of DTI prediction. In addition, many existing computational approaches ignore the behavior information between nodes of the DTI network. In this paper, we develop an ensemble computational approach called integrated multi-similarity fusion and heterogeneous graph inference. First, based on the known DTI network, the degree distribution of drug and target similarities are analyzed and the noise and useless information are removed to improve prediction accuracy. Second, based on drug and target similarities and known DTIs, a strategy of multi-similarity fusion is proposed to capture potential useful information from known interactions that is used for enhancing drug and target similarities. Third, the heterogeneous graph inference is used to predict the DTIs to capture the edge weight (closeness) and behavior information (diffusion) between nodes of a heterogeneous network. To assist the reproducibility of our work and its comparison to published results, we perform experiments on four benchmark datasets. Results show that our approach outperforms some existing approaches and can contribute to predicting potential DTIs.

Heterogeneous graph inference with matrix completion for computational drug repositioning.

Emerging evidence presents that traditional drug discovery experiment is time-consuming and high costs. Computational drug repositioning plays a critical role in saving time and resources for drug research and discovery. Therefore, developing more accurate and efficient approaches is imperative. Heterogeneous graph inference is a classical method in computational drug repositioning, which not only has high convergence precision, but also has fast convergence speed. However, the method has not fully considered the sparsity of heterogeneous association network. In addition, rough similarity measure can reduce the performance in identifying drug-associated indications. In this article, we propose a heterogeneous graph inference with matrix completion (HGIMC) method to predict potential indications for approved and novel drugs. First, we use a bounded matrix completion (BMC) model to prefill a part of the missing entries in original drug-disease association matrix. This step can add more positive and formative drug-disease edges between drug network and disease network. Second, Gaussian radial basis function (GRB) is employed to improve the drug and disease similarities since the performance of heterogeneous graph inference more relies on similarity measures. Next, based on the updated drug-disease associations and new similarity measures of drug and disease, we construct a novel heterogeneous drug-disease network. Finally, HGIMC utilizes the heterogeneous network to infer the scores of unknown association pairs, and then recommend the promising indications for drugs. To evaluate the performance of our method, HGIMC is compared with five state-of-the-art approaches of drug repositioning in the 10-fold cross-validation and de novo tests. As the numerical results shown, HGIMC not only achieves a better prediction performance but also has an excellent computation efficiency. In addition, cases studies also confirm the effectiveness of our method in practical application. The HGIMC software and data are freely available at https://github.com/BioinformaticsCSU/HGIMC, https://hub.docker.com/repository/docker/yangmy84/hgimc and http://doi.org/10.5281/zenodo.4285640. Supplementary data are available at Bioinformatics online.

Heterogeneous graph inference based on similarity network fusion for predicting lncRNA-miRNA interaction.

LncRNA and miRNA are two non-coding RNA types that are popular in current research. LncRNA interacts with miRNA to regulate gene transcription, further affecting human health and disease. Accurate identification of lncRNA–miRNA interactions contributes to the in-depth study of the biological functions and mechanisms of non-coding RNA. However, relying on biological experiments to obtain interaction information is time-consuming and expensive. Considering the rapid accumulation of gene information and the few computational methods, it is urgent to supplement the effective computational models to predict lncRNA–miRNA interactions. In this work, we propose a heterogeneous graph inference method based on similarity network fusion (SNFHGILMI) to predict potential lncRNA–miRNA interactions. First, we calculated multiple similarity data, including lncRNA sequence similarity, miRNA sequence similarity, lncRNA Gaussian nuclear similarity, and miRNA Gaussian nuclear similarity. Second, the similarity network fusion method was employed to integrate the data and get the similarity network of lncRNA and miRNA. Then, we constructed a bipartite network by combining the known interaction network and similarity network of lncRNA and miRNA. Finally, the heterogeneous graph inference method was introduced to construct a prediction model. On the real dataset, the model SNFHGILMI achieved AUC of 0.9501 and 0.9426 ± 0.0035 based on LOOCV and 5-fold cross validation, respectively. Furthermore, case studies also demonstrate that SNFHGILMI is a high-performance prediction method that can accurately predict new lncRNA–miRNA interactions. The Matlab code and readme file of SNFHGILMI can be downloaded from https://github.com/cj-DaSE/SNFHGILMI.

Crosstalk between microRNAs, the putative target genes and the lncRNA network in metabolic diseases.

MicroRNAs (miRNAs/miRs) are small non-coding RNAs (ncRNAs) that regulate gene expression. Emerging knowledge has suggested that miRNAs have a role in the pathogenesis of metabolic disorders, supporting the hypothesis that miRNAs may represent potential biomarkers or targets for this set of diseases. However, the current evidence is often controversial. Therefore, the aim of the present study was to determine the associations between miRNAs-target genes, miRNA-long ncRNAs (lncRNAs), and miRNAs-small molecules in human metabolic diseases, including obesity, type 2 diabetes and non-alcoholic fatty liver disease. The metabolic disease-related miRNAs were obtained from the Human MicroRNA Disease Database (HMDD) and miR2Disease database. A search on the databases Matrix Decomposition and Heterogeneous Graph Inference (MDHGI) and DisGeNET were also performed. miRNAs target genes were obtained from three independent sources: Microcosm, TargetScan and miRTarBase. The interactions between miRNAs-lncRNA and miRNA-small molecules were performed using the miRNet web tool. The network analyses were performed using Cytoscape software. As a result, a total of 20 miRNAs were revealed to be associated with metabolic disorders in the present study. Notably, 6 miRNAs (miR-17-5p, miR-29c-3p, miR-34a-5p, miR-103a-3p, miR-107 and miR-132-3p) were found in the four resources (HMDD, miR2Disease, MDHGI, and DisGeNET) used for these analyses, presenting a stronger association with the diseases. Furthermore, the target genes of these miRNAs participate in several pathways previously associated with metabolic diseases. In addition, interactions between miRNA-lncRNA and miRNA-small molecules were also found, suggesting that some molecules can modulate gene expression via such an indirect way. Thus, the results of this data mining and integration analysis provide further information on the possible molecular basis of the metabolic disease pathogenesis as well as provide a path to search for potential biomarkers and therapeutic targets concerning metabolic diseases.

Prediction of Small Molecule-MicroRNA Associations by Sparse Learning and Heterogeneous Graph Inference.

As microRNAs (miRNAs) have been reported to be a type of novel high-value small molecule (SM) drug targets for disease treatments, many researchers are engaged in the field of exploring new SM-miRNA associations. Nevertheless, because of the high cost, adopting traditional biological experiments constrains the efficiency of discovering new associations between SMs and miRNAs. Therefore, as an important auxiliary tool, reliable computational models will be of great help to reveal SM-miRNA associations. In this article, we developed a computational model of sparse learning and heterogeneous graph inference for small molecule-miRNA association prediction (SLHGISMMA). Initially, the sparse learning method (SLM) was implemented to decompose the SM-miRNA adjacency matrix. Then, we integrated the reacquired association information together with the similarity information of SMs and miRNAs into a heterogeneous graph to infer potential SM-miRNA associations. Here, the main innovation of SLHGISMMA lies in the introduction of SLM to eliminate noises of the original adjacency matrix to some extent, which plays an important role in performance improvement. In addition, to assess SLHGISMMA' performance, four different kinds of cross-validations were performed based on two datasets. As a result, based on dataset 1 (dataset 2), SLHGISMMA achieved area under the curves of 0.9273 (0.7774), 0.9365 (0.7973), 0.7703 (0.6556), and 0.9241 ± 0.0052 (0.7724 ± 0.0032) in global leave-one-out cross-validation (LOOCV), miRNA-fixed local LOOCV, SM-fixed local LOOCV, and 5-fold cross-validation, respectively. Moreover, in the case study on three important SMs via removing their known associations, the results showed that most of the top 50 predicted miRNAs were confirmed by the database SM2miR v1.0 or the experimental literature.

MDHGI: Matrix Decomposition and Heterogeneous Graph Inference for miRNA-disease association prediction.

Recently, a growing number of biological research and scientific experiments have demonstrated that microRNA (miRNA) affects the development of human complex diseases. Discovering miRNA-disease associations plays an increasingly vital role in devising diagnostic and therapeutic tools for diseases. However, since uncovering associations via experimental methods is expensive and time-consuming, novel and effective computational methods for association prediction are in demand. In this study, we developed a computational model of Matrix Decomposition and Heterogeneous Graph Inference for miRNA-disease association prediction (MDHGI) to discover new miRNA-disease associations by integrating the predicted association probability obtained from matrix decomposition through sparse learning method, the miRNA functional similarity, the disease semantic similarity, and the Gaussian interaction profile kernel similarity for diseases and miRNAs into a heterogeneous network. Compared with previous computational models based on heterogeneous networks, our model took full advantage of matrix decomposition before the construction of heterogeneous network, thereby improving the prediction accuracy. MDHGI obtained AUCs of 0.8945 and 0.8240 in the global and the local leave-one-out cross validation, respectively. Moreover, the AUC of 0.8794+/-0.0021 in 5-fold cross validation confirmed its stability of predictive performance. In addition, to further evaluate the model's accuracy, we applied MDHGI to four important human cancers in three different kinds of case studies. In the first type, 98% (Esophageal Neoplasms) and 98% (Lymphoma) of top 50 predicted miRNAs have been confirmed by at least one of the two databases (dbDEMC and miR2Disease) or at least one experimental literature in PubMed. In the second type of case study, what made a difference was that we removed all known associations between the miRNAs and Lung Neoplasms before implementing MDHGI on Lung Neoplasms. As a result, 100% (Lung Neoplasms) of top 50 related miRNAs have been indexed by at least one of the three databases (dbDEMC, miR2Disease and HMDD V2.0) or at least one experimental literature in PubMed. Furthermore, we also tested our prediction method on the HMDD V1.0 database to prove the applicability of MDHGI to different datasets. The results showed that 50 out of top 50 miRNAs related with the breast neoplasms were validated by at least one of the three databases (HMDD V2.0, dbDEMC, and miR2Disease) or at least one experimental literature.

HGIMDA: Heterogeneous graph inference for miRNA-disease association prediction.

Recently, microRNAs (miRNAs) have drawn more and more attentions because accumulating experimental studies have indicated miRNA could play critical roles in multiple biological processes as well as the development and progression of human complex diseases. Using the huge number of known heterogeneous biological datasets to predict potential associations between miRNAs and diseases is an important topic in the field of biology, medicine, and bioinformatics. In this study, considering the limitations in the previous computational methods, we developed the computational model of Heterogeneous Graph Inference for MiRNA-Disease Association prediction (HGIMDA) to uncover potential miRNA-disease associations by integrating miRNA functional similarity, disease semantic similarity, Gaussian interaction profile kernel similarity, and experimentally verified miRNA-disease associations into a heterogeneous graph. HGIMDA obtained AUCs of 0.8781 and 0.8077 based on global and local leave-one-out cross validation, respectively. Furthermore, HGIMDA was applied to three important human cancers for performance evaluation. As a result, 90% (Colon Neoplasms), 88% (Esophageal Neoplasms) and 88% (Kidney Neoplasms) of top 50 predicted miRNAs are confirmed by recent experiment reports. Furthermore, HGIMDA could be effectively applied to new diseases and new miRNAs without any known associations, which overcome the important limitations of many previous computational models.