OGNNMDA: a computational model for microbe-drug association prediction based on ordered message-passing graph neural networks.

In recent years, many excellent computational models have emerged in microbe-drug association prediction, but their performance still has room for improvement. This paper proposed the OGNNMDA framework, which applied an ordered message-passing mechanism to distinguish the different neighbor information in each message propagation layer, and it achieved a better embedding ability through deeper network layers. Firstly, the method calculates four similarity matrices based on microbe functional similarity, drug chemical structure similarity, and their respective Gaussian interaction profile kernel similarity. After integrating these similarity matrices, it concatenates the integrated similarity matrix with the known association matrix to obtain the microbe-drug heterogeneous matrix. Secondly, it uses a multi-layer ordered message-passing graph neural network encoder to encode the heterogeneous network and the known association information adjacency matrix, thereby obtaining the final embedding features of the microbe-drugs. Finally, it inputs the embedding features into the bilinear decoder to get the final prediction results. The OGNNMDA method performed comparative experiments, ablation experiments, and case studies on the aBiofilm, MDAD and DrugVirus datasets using 5-fold cross-validation. The experimental results showed that OGNNMDA showed the strongest prediction performance on aBiofilm and MDAD and obtained sub-optimal results on DrugVirus. In addition, the case studies on well-known drugs and microbes also support the effectiveness of the OGNNMDA method. Source codes and data are available at: https://github.com/yyzg/OGNNMDA.

GSAMDA: a computational model for predicting potential microbe-drug associations based on graph attention network and sparse autoencoder.

BACKGROUND: Clinical studies show that microorganisms are closely related to human health, and the discovery of potential associations between microbes and drugs will facilitate drug research and development. However, at present, few computational methods for predicting microbe-drug associations have been proposed. RESULTS: In this work, we proposed a novel computational model named GSAMDA based on the graph attention network and sparse autoencoder to infer latent microbe-drug associations. In GSAMDA, we first built a heterogeneous network through integrating known microbe-drug associations, microbe similarities and drug similarities. And then, we adopted a GAT-based autoencoder and a sparse autoencoder module respectively to learn topological representations and attribute representations for nodes in the newly constructed heterogeneous network. Finally, based on these two kinds of node representations, we constructed two kinds of feature matrices for microbes and drugs separately, and then, utilized them to calculate possible association scores for microbe-drug pairs. CONCLUSION: A novel computational model is proposed for predicting potential microbe-drug associations based on graph attention network and sparse autoencoder. Compared with other five state-of-the-art competitive methods, the experimental results illustrated that our model can achieve better performance. Moreover, case studies on two categories of representative drugs and microbes further demonstrated the effectiveness of our model as well.

Review on predicting pairwise relationships between human microbes, drugs and diseases: from biological data to computational models.

In recent years, with the rapid development of techniques in bioinformatics and life science, a considerable quantity of biomedical data has been accumulated, based on which researchers have developed various computational approaches to discover potential associations between human microbes, drugs and diseases. This paper provides a comprehensive overview of recent advances in prediction of potential correlations between microbes, drugs and diseases from biological data to computational models. Firstly, we introduced the widely used datasets relevant to the identification of potential relationships between microbes, drugs and diseases in detail. And then, we divided a series of a lot of representative computing models into five major categories including network, matrix factorization, matrix completion, regularization and artificial neural network for in-depth discussion and comparison. Finally, we analysed possible challenges and opportunities in this research area, and at the same time we outlined some suggestions for further improvement of predictive performances as well.

Identification of Essential Proteins Based on Local Random Walk and Adaptive Multi-View Multi-Label Learning.

Accumulating evidences have indicated that essential proteins play vital roles in human physiological process. In recent years, although researches on prediction of essential proteins have been developing rapidly, there are as well various limitations such as unsatisfactory data suitability, low accuracy of predictive results and so on. In this manuscript, a novel method called RWAMVL was proposed to predict essential proteins based on the Random Walk and the Adaptive Multi-View multi-label Learning. In RWAMVL, considering that the inherent noise is ubiquitous in existing datasets of known protein-protein interactions (PPIs), a variety of different features including biological features of proteins and topological features of PPI networks were obtained by adopting adaptive multi-view multi-label learning first. And then, an improved random walk method was designed to detect essential proteins based on these different features. Finally, in order to verify the predictive performance of RWAMVL, intensive experiments were done to compare it with multiple state-of-the-art predictive methods under different expeditionary frameworks. And as a result, RWAMVL was proven that it can achieve better prediction accuracy than all those competitive methods, which demonstrated as well that RWAMVL may be a potential tool for prediction of key proteins in the future.

Multi-Similarities Bilinear Matrix Factorization-Based Method for Predicting Human Microbe-Disease Associations.

Accumulating studies have shown that microbes are closely related to human diseases. In this paper, a novel method called MSBMFHMDA was designed to predict potential microbe-disease associations by adopting multi-similarities bilinear matrix factorization. In MSBMFHMDA, a microbe multiple similarities matrix was constructed first based on the Gaussian interaction profile kernel similarity and cosine similarity for microbes. Then, we use the Gaussian interaction profile kernel similarity, cosine similarity, and symptom similarity for diseases to compose the disease multiple similarities matrix. Finally, we integrate these two similarity matrices and the microbe-disease association matrix into our model to predict potential associations. The results indicate that our method can achieve reliable AUCs of 0.9186 and 0.9043 ± 0.0048 in the framework of leave-one-out cross validation (LOOCV) and fivefold cross validation, respectively. What is more, experimental results indicated that there are 10, 10, and 8 out of the top 10 related microbes for asthma, inflammatory bowel disease, and type 2 diabetes mellitus, respectively, which were confirmed by experiments and literatures. Therefore, our model has favorable performance in predicting potential microbe-disease associations.

A Novel Collaborative Filtering Model-Based Method for Identifying Essential Proteins.

Considering that traditional biological experiments are expensive and time consuming, it is important to develop effective computational models to infer potential essential proteins. In this manuscript, a novel collaborative filtering model-based method called CFMM was proposed, in which, an updated protein-domain interaction (PDI) network was constructed first by applying collaborative filtering algorithm on the original PDI network, and then, through integrating topological features of PDI networks with biological features of proteins, a calculative method was designed to infer potential essential proteins based on an improved PageRank algorithm. The novelties of CFMM lie in construction of an updated PDI network, application of the commodity-customer-based collaborative filtering algorithm, and introduction of the calculation method based on an improved PageRank algorithm, which ensured that CFMM can be applied to predict essential proteins without relying entirely on known protein-domain associations. Simulation results showed that CFMM can achieve reliable prediction accuracies of 92.16, 83.14, 71.37, 63.87, 55.84, and 52.43% in the top 1, 5, 10, 15, 20, and 25% predicted candidate key proteins based on the DIP database, which are remarkably higher than 14 competitive state-of-the-art predictive models as a whole, and in addition, CFMM can achieve satisfactory predictive performances based on different databases with various evaluation measurements, which further indicated that CFMM may be a useful tool for the identification of essential proteins in the future.

A Novel Model for Identifying Essential Proteins Based on Key Target Convergence Sets.

In recent years, many computational models have been designed to detect essential proteins based on protein-protein interaction (PPI) networks. However, due to the incompleteness of PPI networks, the prediction accuracy of these models is still not satisfactory. In this manuscript, a novel key target convergence sets based prediction model (KTCSPM) is proposed to identify essential proteins. In KTCSPM, a weighted PPI network and a weighted (Domain-Domain Interaction) network are constructed first based on known PPIs and PDIs downloaded from benchmark databases. And then, by integrating these two kinds of networks, a novel weighted PDI network is built. Next, through assigning a unique key target convergence set (KTCS) for each node in the weighted PDI network, an improved method based on the random walk with restart is designed to identify essential proteins. Finally, in order to evaluate the predictive effects of KTCSPM, it is compared with 12 competitive state-of-the-art models, and experimental results show that KTCSPM can achieve better prediction accuracy. Considering the satisfactory predictive performance achieved by KTCSPM, it indicates that KTCSPM might be a good supplement to the future research on prediction of essential proteins.

Method for Identifying Essential Proteins by Key Features of Proteins in a Novel Protein-Domain Network.

In recent years, due to low accuracy and high costs of traditional biological experiments, more and more computational models have been proposed successively to infer potential essential proteins. In this paper, a novel prediction method called KFPM is proposed, in which, a novel protein-domain heterogeneous network is established first by combining known protein-protein interactions with known associations between proteins and domains. Next, based on key topological characteristics extracted from the newly constructed protein-domain network and functional characteristics extracted from multiple biological information of proteins, a new computational method is designed to effectively integrate multiple biological features to infer potential essential proteins based on an improved PageRank algorithm. Finally, in order to evaluate the performance of KFPM, we compared it with 13 state-of-the-art prediction methods, experimental results show that, among the top 1, 5, and 10% of candidate proteins predicted by KFPM, the prediction accuracy can achieve 96.08, 83.14, and 70.59%, respectively, which significantly outperform all these 13 competitive methods. It means that KFPM may be a meaningful tool for prediction of potential essential proteins in the future.

Method for Essential Protein Prediction Based on a Novel Weighted Protein-Domain Interaction Network.

In recent years a number of calculative models based on protein-protein interaction (PPI) networks have been proposed successively. However, due to false positives, false negatives, and the incompleteness of PPI networks, there are still many challenges affecting the design of computational models with satisfactory predictive accuracy when inferring key proteins. This study proposes a prediction model called WPDINM for detecting key proteins based on a novel weighted protein-domain interaction (PDI) network. In WPDINM, a weighted PPI network is constructed first by combining the gene expression data of proteins with topological information extracted from the original PPI network. Simultaneously, a weighted domain-domain interaction (DDI) network is constructed based on the original PDI network. Next, through integrating the newly obtained weighted PPI network and weighted DDI network with the original PDI network, a weighted PDI network is further constructed. Then, based on topological features and biological information, including the subcellular localization and orthologous information of proteins, a novel PageRank-based iterative algorithm is designed and implemented on the newly constructed weighted PDI network to estimate the criticality of proteins. Finally, to assess the prediction performance of WPDINM, we compared it with 12 kinds of competitive measures. Experimental results show that WPDINM can achieve a predictive accuracy rate of 90.19, 81.96, 70.72, 62.04, 55.83, and 51.13% in the top 1%, top 5%, top 10%, top 15%, top 20%, and top 25% separately, which exceeds the prediction accuracy achieved by traditional state-of-the-art competing measures. Owing to the satisfactory identification effect, the WPDINM measure may contribute to the further development of key protein identification.

ICLRBBN: a tool for accurate prediction of potential lncRNA disease associations.

Growing evidence has elucidated that long non-coding RNAs (lncRNAs) are involved in a variety of complex diseases in human bodies. In recent years, it has become a hot topic to develop effective computational models to identify potential lncRNA-disease associations. In this article, a novel method called ICLRBBN (Internal Confidence-Based Local Radial Basis Biological Network) is proposed to detect potential lncRNA-disease associations by adopting an internal confidence-based radial basis biological network. In ICLRBBN, a novel internal confidence-based collaborative filtering recommendation algorithm was designed first to mine hidden features between lncRNAs and diseases, which guarantees that ICLRBBN can be more effectively applied to predict new diseases. Then, a unique three-layer local radial basis function network consisting of diseases and lncRNAs was constructed, based on which the association probability between diseases and lncRNAs was calculated by combining different characteristics of lncRNAs with local information of diseases. Finally, we compared ICLRBBN with 6 state-of-the-art methods based on two different validation frameworks. Simulation results showed that area under the receiver operating characteristic curve (AUC) values achieved by ICLRBBN outperformed all competing methods. Furthermore, case studies illustrated that ICLRBBN has a promising future as a powerful tool in the practical application of lncRNA-disease association prediction. A web service for prediction of potential lncRNA-disease associations is available at http://leelab2997.cn/.

A novel computational model for predicting potential LncRNA-disease associations based on both direct and indirect features of LncRNA-disease pairs.

BACKGROUND: Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are closely associated with human diseases, and it is useful for the diagnosis and treatment of diseases to get the relationships between lncRNAs and diseases. Due to the high costs and time complexity of traditional bio-experiments, in recent years, more and more computational methods have been proposed by researchers to infer potential lncRNA-disease associations. However, there exist all kinds of limitations in these state-of-the-art prediction methods as well. RESULTS: In this manuscript, a novel computational model named FVTLDA is proposed to infer potential lncRNA-disease associations. In FVTLDA, its major novelty lies in the integration of direct and indirect features related to lncRNA-disease associations such as the feature vectors of lncRNA-disease pairs and their corresponding association probability fractions, which guarantees that FVTLDA can be utilized to predict diseases without known related-lncRNAs and lncRNAs without known related-diseases. Moreover, FVTLDA neither relies solely on known lncRNA-disease nor requires any negative samples, which guarantee that it can infer potential lncRNA-disease associations more equitably and effectively than traditional state-of-the-art prediction methods. Additionally, to avoid the limitations of single model prediction techniques, we combine FVTLDA with the Multiple Linear Regression (MLR) and the Artificial Neural Network (ANN) for data analysis respectively. Simulation experiment results show that FVTLDA with MLR can achieve reliable AUCs of 0.8909, 0.8936 and 0.8970 in 5-Fold Cross Validation (fivefold CV), 10-Fold Cross Validation (tenfold CV) and Leave-One-Out Cross Validation (LOOCV), separately, while FVTLDA with ANN can achieve reliable AUCs of 0.8766, 0.8830 and 0.8807 in fivefold CV, tenfold CV, and LOOCV respectively. Furthermore, in case studies of gastric cancer, leukemia and lung cancer, experiment results show that there are 8, 8 and 8 out of top 10 candidate lncRNAs predicted by FVTLDA with MLR, and 8, 7 and 8 out of top 10 candidate lncRNAs predicted by FVTLDA with ANN, having been verified by recent literature. Comparing with the representative prediction model of KATZLDA, comparison results illustrate that FVTLDA with MLR and FVTLDA with ANN can achieve the average case study contrast scores of 0.8429 and 0.8515 respectively, which are both notably higher than the average case study contrast score of 0.6375 achieved by KATZLDA. CONCLUSION: The simulation results show that FVTLDA has good prediction performance, which is a good supplement to future bioinformatics research.

BHCMDA: A New Biased Heat Conduction Based Method for Potential MiRNA-Disease Association Prediction.

Recent studies have indicated that microRNAs (miRNAs) are closely related to sundry human sophisticated diseases. According to the surmise that functionally similar miRNAs are more likely associated with phenotypically similar diseases, researchers have proposed a variety of valid computational models through integrating known miRNA-disease associations, disease semantic similarity, miRNA functional similarity, and Gaussian interaction profile kernel similarity to discover the potential miRNA-disease relationships in biomedical researches. Taking account of the limitations of previous computational models, a new computational model based on biased heat conduction for MiRNA-Disease Association prediction (BHCMDA) was proposed in this paper, which can achieve the AUC of 0.8890 in LOOCV (Leave-One-Out Cross Validation) and the mean AUC of 0.9060, 0.8931 under the framework of twofold cross validation, fivefold cross validation, respectively. In addition, BHCMDA was further implemented to the case studies of three vital human cancers, and simulation results illustrated that there were 88% (Esophageal Neoplasms), 92% (Colonic Neoplasms) and 92% (Lymphoma) out of top 50 predicted miRNAs having been confirmed by experimental literatures, separately, which demonstrated the good performance of BHCMDA as well. Thence, BHCMDA would be a useful calculative resource for potential miRNA-disease association prediction.

A Novel Method for LncRNA-Disease Association Prediction Based on an lncRNA-Disease Association Network.

An increasing number of studies have indicated that long-non-coding RNAs (lncRNAs) play critical roles in many important biological processes. Predicting potential lncRNA-disease associations can improve our understanding of the molecular mechanisms of human diseases and aid in finding biomarkers for disease diagnosis, treatment, and prevention. In this paper, we constructed a bipartite network based on known lncRNA-disease associations; based on this work, we proposed a novel model for inferring potential lncRNA-disease associations. Specifically, we analyzed the properties of the bipartite network and found that it closely followed a power-law distribution. Moreover, to evaluate the performance of our model, a leave-one-out cross-validation (LOOCV) framework was implemented, and the simulation results showed that our computational model significantly outperformed previous state-of-the-art models, with AUCs of 0.8825, 0.9004, and 0.9292 for known lncRNA-disease associations obtained from the LncRNADisease database, Lnc2Cancer database, and MNDR database, respectively. Thus, our approach may be an excellent addition to the biomedical research field in the future.

A Novel Approach for Predicting Disease-lncRNA Associations Based on the Distance Correlation Set and Information of the miRNAs.

Recently, accumulating laboratorial studies have indicated that plenty of long noncoding RNAs (lncRNAs) play important roles in various biological processes and are associated with many complex human diseases. Therefore, developing powerful computational models to predict correlation between lncRNAs and diseases based on heterogeneous biological datasets will be important. However, there are few approaches to calculating and analyzing lncRNA-disease associations on the basis of information about miRNAs. In this article, a new computational method based on distance correlation set is developed to predict lncRNA-disease associations (DCSLDA). Comparing with existing state-of-the-art methods, we found that the major novelty of DCSLDA lies in the introduction of lncRNA-miRNA-disease network and distance correlation set; thus DCSLDA can be applied to predict potential lncRNA-disease associations without requiring any known disease-lncRNA associations. Simulation results show that DCSLDA can significantly improve previous existing models with reliable AUC of 0.8517 in the leave-one-out cross-validation. Furthermore, while implementing DCSLDA to prioritize candidate lncRNAs for three important cancers, in the first 0.5% of forecast results, 17 predicted associations are verified by other independent studies and biological experimental studies. Hence, it is anticipated that DCSLDA could be a great addition to the biomedical research field.

A Novel Probability Model for LncRNA⁻Disease Association Prediction Based on the Naïve Bayesian Classifier.

An increasing number of studies have indicated that long-non-coding RNAs (lncRNAs) play crucial roles in biological processes, complex disease diagnoses, prognoses, and treatments. However, experimentally validated associations between lncRNAs and diseases are still very limited. Recently, computational models have been developed to discover potential associations between lncRNAs and diseases by integrating multiple heterogeneous biological data; this has become a hot topic in biological research. In this article, we constructed a global tripartite network by integrating a variety of biological information including miRNA⁻disease, miRNA⁻lncRNA, and lncRNA⁻disease associations and interactions. Then, we constructed a global quadruple network by appending gene⁻lncRNA interaction, gene⁻disease association, and gene⁻miRNA interaction networks to the global tripartite network. Subsequently, based on these two global networks, a novel approach was proposed based on the naïve Bayesian classifier to predict potential lncRNA⁻disease associations (NBCLDA). Comparing with the state-of-the-art methods, our new method does not entirely rely on known lncRNA⁻disease associations, and can achieve a reliable performance with effective area under ROC curve (AUCs)in leave-one-out cross validation. Moreover, in order to further estimate the performance of NBCLDA, case studies of colorectal cancer, prostate cancer, and glioma were implemented in this paper, and the simulation results demonstrated that NBCLDA can be an excellent tool for biomedical research in the future.

Prediction of microRNA-disease associations based on distance correlation set.

BACKGROUND: Recently, numerous laboratory studies have indicated that many microRNAs (miRNAs) are involved in and associated with human diseases and can serve as potential biomarkers and drug targets. Therefore, developing effective computational models for the prediction of novel associations between diseases and miRNAs could be beneficial for achieving an understanding of disease mechanisms at the miRNA level and the interactions between diseases and miRNAs at the disease level. Thus far, only a few miRNA-disease association pairs are known, and models analyzing miRNA-disease associations based on lncRNA are limited. RESULTS: In this study, a new computational method based on a distance correlation set is developed to predict miRNA-disease associations (DCSMDA) by integrating known lncRNA-disease associations, known miRNA-lncRNA associations, disease semantic similarity, and various lncRNA and disease similarity measures. The novelty of DCSMDA is due to the construction of a miRNA-lncRNA-disease network, which reveals that DCSMDA can be applied to predict potential lncRNA-disease associations without requiring any known miRNA-disease associations. Although the implementation of DCSMDA does not require known disease-miRNA associations, the area under curve is 0.8155 in the leave-one-out cross validation. Furthermore, DCSMDA was implemented in case studies of prostatic neoplasms, lung neoplasms and leukaemia, and of the top 10 predicted associations, 10, 9 and 9 associations, respectively, were separately verified in other independent studies and biological experimental studies. In addition, 10 of the 10 (100%) associations predicted by DCSMDA were supported by recent bioinformatical studies. CONCLUSIONS: According to the simulation results, DCSMDA can be a great addition to the biomedical research field.

A Novel Approach Based on a Weighted Interactive Network to Predict Associations of MiRNAs and Diseases.

Accumulating evidence progressively indicated that microRNAs (miRNAs) play a significant role in the pathogenesis of diseases through many experimental studies; therefore, developing powerful computational models to identify potential human miRNA⁻disease associations is vital for an understanding of the disease etiology and pathogenesis. In this paper, a weighted interactive network was firstly constructed by combining known miRNA⁻disease associations, as well as the integrated similarity between diseases and the integrated similarity between miRNAs. Then, a new computational method implementing the newly weighted interactive network was developed for discovering potential miRNA⁻disease associations (WINMDA) by integrating the T most similar neighbors and the shortest path algorithm. Simulation results show that WINMDA can achieve reliable area under the receiver operating characteristics (ROC) curve (AUC) results of 0.9183 ± 0.0007 in 5-fold cross-validation, 0.9200 ± 0.0004 in 10-fold cross-validation, 0.9243 in global leave-one-out cross-validation (LOOCV), and 0.8856 in local LOOCV. Furthermore, case studies of colon neoplasms, gastric neoplasms, and prostate neoplasms based on the Human microRNA Disease Database (HMDD) database were implemented, for which 94% (colon neoplasms), 96% (gastric neoplasms), and 96% (prostate neoplasms) of the top 50 predicting miRNAs were confirmed by recent experimental reports, which also demonstrates that WINMDA can effectively uncover potential miRNA⁻disease associations.