Potential Disease-related miRNAs Research Articles

Meta-Path Semantic and Global-Local Representation Learning Enhanced Graph Convolutional Model for Disease-Related miRNA Prediction.

Dysregulation of miRNAs is closely related to the progression of various diseases, so identifying disease-related miRNAs is crucial. Most recently proposed methods are based on graph reasoning, while they did not completely exploit the topological structure composed of the higher-order neighbor nodes and the global and local features of miRNA and disease nodes. We proposed a prediction method, MDAP, to learn semantic features of miRNA and disease nodes based on various meta-paths, as well as node features from the entire heterogeneous network perspective, and node pair attributes. Firstly, for both the miRNA and disease nodes, node category- wise meta-paths were constructed to integrate the similarity and association connection relationships. Each target node has its specific neighbor nodes for each meta-path, and the neighbors of longer meta-paths constitute its higher-order neighbor topological structure. Secondly, we constructed a meta-path specific graph convolutional network module to integrate the features of higher-order neighbors and their topology, and then learned the semantic representations of nodes. Thirdly, for the entire miRNA-disease heterogeneous network, a global-aware graph convolutional autoencoder was built to learn the network-view feature representations of nodes. We also designed semantic-level and representation-level attentions to obtain informative semantic features and node representations. Finally, the strategy based on the parallel convolutional-deconvolutional neural networks were designed to enhance the local feature learning for a pair of miRNA and disease nodes. The experiment results showed that MDAP outperformed other state-of-the-art methods, and the ablation experiments demonstrated the effectiveness of MDAP's major innovations. MDAP's ability in discovering potential disease-related miRNAs was further analyzed by the case studies over three diseases.

A Multi-Relational Graph Encoder Network for Fine-Grained Prediction of MiRNA-Disease Associations.

MicroRNAs (miRNAs) are critical in diagnosing and treating various diseases. Automatically demystifying the interdependent relationships between miRNAs and diseases has recently made remarkable progress, but their fine-grained interactive relationships still need to be explored. We propose a multi-relational graph encoder network for fine-grained prediction of miRNA-disease associations (MRFGMDA), which uses practical and current datasets to construct a multi-relational graph encoder network to predict disease-related miRNAs and their specific relationship types (upregulation, downregulation, or dysregulation). We evaluated MRFGMDA and found that it accurately predicted miRNA-disease associations, which could have far-reaching implications for clinical medical analysis, early diagnosis, prevention, and treatment. Case analyses, Kaplan-Meier survival analysis, expression difference analysis, and immune infiltration analysis further demonstrated the effectiveness and feasibility of MRFGMDA in uncovering potential disease-related miRNAs. Overall, our work represents a significant step toward improving the prediction of miRNA-disease associations using a fine-grained approach could lead to more accurate diagnosis and treatment of diseases.

Application of Bidirectional Generative Adversarial Networks to Predict Potential miRNAs Associated With Diseases.

Substantial evidence has shown that microRNAs are crucial for biological processes within complex human diseases. Identifying the association of miRNA–disease pairs will contribute to accelerating the discovery of potential biomarkers and pathogenesis. Researchers began to focus on constructing computational models to facilitate the progress of disease pathology and clinical medicine by identifying the potential disease-related miRNAs. However, most existing computational methods are expensive, and their use is limited to unobserved relationships for unknown miRNAs (diseases) without association information. In this manuscript, we proposed a creatively semi-supervised model named bidirectional generative adversarial network for miRNA-disease association prediction (BGANMDA). First, we constructed a microRNA similarity network, a disease similarity network, and Gaussian interaction profile kernel similarity based on the known miRNA–disease association and comprehensive similarity of miRNAs (diseases). Next, an integrated similarity feature network with the full underlying relationships of miRNA–disease pairwise was obtained. Then, the similarity feature network was fed into the BGANMDA model to learn advanced traits in latent space. Finally, we ranked an association score list and predicted the associations between miRNA and disease. In our experiment, a five-fold cross validation was applied to estimate BGANMDA’s performance, and an area under the curve (AUC) of 0.9319 and a standard deviation of 0.00021 were obtained. At the same time, in the global and local leave-one-out cross validation (LOOCV), the AUC value and standard deviation of BGANMDA were 0.9116 ± 0.0025 and 0.8928 ± 0.0022, respectively. Furthermore, BGANMDA was employed in three different case studies to validate its prediction capability and accuracy. The experimental results of the case studies showed that 46, 46, and 48 of the top 50 prediction lists had been identified in previous studies.

DNRLCNN: A CNN Framework for Identifying MiRNA-Disease Associations Using Latent Feature Matrix Extraction with Positive Samples.

Emerging evidence indicates that miRNAs have strong relationships with many human diseases. Investigating the associations will contribute to elucidating the activities of miRNAs and pathogenesis mechanisms, and providing new opportunities for disease diagnosis and drug discovery. Therefore, it is of significance to identify potential associations between miRNAs and diseases. The existing databases about the miRNA-disease associations (MDAs) only provide the known MDAs, which can be regarded as positive samples. However, the unknown MDAs are not sufficient to regard as reliable negative samples. To deal with this uncertainty, we proposed a convolutional neural network (CNN) framework, named DNRLCNN, based on a latent feature matrix extracted by only positive samples to predict MDAs. First, by only considering the positive samples into the calculation process, we captured the latent feature matrix for complex interactions between miRNAs and diseases in low-dimensional space. Then, we constructed a feature vector for each miRNA and disease pair based on the feature representation. Finally, we adopted a modified CNN for the feature vector to predict MDAs. As a result, our model achieves better performance than other state-of-the-art methods which based CNN in fivefold cross-validation on both miRNA-disease association prediction task (average AUC of 0.9030) and miRNA-phenotype association prediction task (average AUC of 0. 9442). In addition, we carried out case studies on two human diseases, and all the top-50 predicted miRNAs for lung neoplasms are confirmed by HMDD v3.2 and dbDEMC 2.0 databases, 98% of the top-50 predicted miRNAs for heart failure are confirmed. The experiment results show that our model has the capability of inferring potential disease-related miRNAs.

Identification of miRNA–disease associations via deep forest ensemble learning based on autoencoder

Increasing evidences show that the occurrence of human complex diseases is closely related to microRNA (miRNA) variation and imbalance. For this reason, predicting disease-related miRNAs is essential for the diagnosis and treatment of complex human diseases. Although some current computational methods can effectively predict potential disease-related miRNAs, the accuracy of prediction should be further improved. In our study, a new computational method via deep forest ensemble learning based on autoencoder (DFELMDA) is proposed to predict miRNA-disease associations. Specifically, a new feature representation strategy is proposed to obtain different types of feature representations (from miRNA and disease) for each miRNA-disease association. Then, two types of low-dimensional feature representations are extracted by two deep autoencoders for predicting miRNA-disease associations. Finally, two prediction scores of the miRNA-disease associations are obtained by the deep random forest and combined to determine the final results. DFELMDA is compared with several classical methods on the The Human microRNA Disease Database (HMDD) dataset. Results reveal that the performance of this method is superior. The area under receiver operating characteristic curve (AUC) values obtained by DFELMDA through 5-fold and 10-fold cross-validation are 0.9552 and 0.9560, respectively. In addition, case studies on colon, breast and lung tumors of different disease types further demonstrate the excellent ability of DFELMDA to predict disease-associated miRNA-disease. Performance analysis shows that DFELMDA can be used as an effective computational tool for predicting miRNA-disease associations.

Predicting miRNA-disease associations using an ensemble learning framework with resampling method.

Accumulating evidences have indicated that microRNA (miRNA) plays a crucial role in the pathogenesis and progression of various complex diseases. Inferring disease-associated miRNAs is significant to explore the etiology, diagnosis and treatment of human diseases. As the biological experiments are time-consuming and labor-intensive, developing effective computational methods has become indispensable to identify associations between miRNAs and diseases. We present an Ensemble learning framework with Resampling method for MiRNA-Disease Association (ERMDA) prediction to discover potential disease-related miRNAs. Firstly, the resampling strategy is proposed for building multiple different balanced training subsets to address the challenge of sample imbalance within the database. Then, ERMDA extracts miRNA and disease feature representations by integrating miRNA-miRNA similarities, disease-disease similarities and experimentally verified miRNA-disease association information. Next, the feature selection approach is applied to reduce the redundant information and increase the diversity among these subsets. Lastly, ERMDA constructs an individual learner on each subset to yield primitive outcomes, and the soft voting method is introduced for making the final decision based on the prediction results of individual learners. A series of experimental results demonstrates that ERMDA outperforms other state-of-the-art methods on both balanced and unbalanced testing sets. Besides, case studies conducted on the three human diseases further confirm the ERMDA's prediction capability for identifying potential disease-related miRNAs. In conclusion, these experimental results demonstrate that our method can serve as an effective and reliable tool for researchers to explore the regulatory role of miRNAs in complex diseases.

A novel miRNA-disease association prediction model using dual random walk with restart and space projection federated method.

A large number of studies have shown that the variation and disorder of miRNAs are important causes of diseases. The recognition of disease-related miRNAs has become an important topic in the field of biological research. However, the identification of disease-related miRNAs by biological experiments is expensive and time consuming. Thus, computational prediction models that predict disease-related miRNAs must be developed. A novel network projection-based dual random walk with restart (NPRWR) was used to predict potential disease-related miRNAs. The NPRWR model aims to estimate and accurately predict miRNA–disease associations by using dual random walk with restart and network projection technology, respectively. The leave-one-out cross validation (LOOCV) was adopted to evaluate the prediction performance of NPRWR. The results show that the area under the receiver operating characteristic curve(AUC) of NPRWR was 0.9029, which is superior to that of other advanced miRNA–disease associated prediction methods. In addition, lung and kidney neoplasms were selected to present a case study. Among the first 50 miRNAs predicted, 50 and 49 miRNAs have been proven by in databases or relevant literature. Moreover, NPRWR can be used to predict isolated diseases and new miRNAs. LOOCV and the case study achieved good prediction results. Thus, NPRWR will become an effective and accurate disease–miRNA association prediction model.

FCGCNMDA: predicting miRNA-disease associations by applying fully connected graph convolutional networks.

Growing evidence indicates that the development and progression of multiple complex diseases are influenced by microRNA (miRNA). Identifying more miRNAs as biomarkers for clinical diagnosis, treatment and prognosis is vital to promote the development of bioinformatics and medicine. Considering that the traditional biological experimental methods are generally time-consuming and expensive, high-efficient computational methods are encouraged to uncover potential disease-related miRNAs. In this paper, FCGCNMDA is presented to predict latent miRNA-disease associations by utilizing fully connected graph convolutional networks. Specially, our method first constructs a fully connected graph in which edge weights represent correlation coefficient between any two pairs of miRNA-disease pair, and then feeds this fully connected graph along with miRNA-disease pairs feature matrix into a two-layer graph convolutional networks (GCN) for training. At last, we utilize the trained network to predict the scores for unknown miRNA-disease pairs. As a result, FCGCNMDA achieves AUC value of [Formula: see text] and AUPRC value of [Formula: see text] in HMDD v2.0 based on five-fold cross validation. Moreover, case studies on Lymphoma, Breast Neoplasms and Prostate Neoplasms shown that 98%, 98%, 98% of the top 50 selected miRNAs were validated by recent experimental evidence. From above results, we can deduce that FCGCNMDA can be regarded as reliable method for potential miRNA-disease associations prediction.

Improved Prediction of miRNA-Disease Associations Based on Matrix Completion with Network Regularization.

The identification of potential microRNA (miRNA)-disease associations enables the elucidation of the pathogenesis of complex human diseases owing to the crucial role of miRNAs in various biologic processes and it yields insights into novel prognostic markers. In the consideration of the time and costs involved in wet experiments, computational models for finding novel miRNA-disease associations would be a great alternative. However, computational models, to date, are biased towards known miRNA-disease associations; this is not suitable for rare miRNAs (i.e., miRNAs with a few known disease associations) and uncommon diseases (i.e., diseases with a few known miRNA associations). This leads to poor prediction accuracies. The most straightforward way of improving the performance is by increasing the number of known miRNA-disease associations. However, due to lack of information, increasing attention has been paid to developing computational models that can handle insufficient data via a technical approach. In this paper, we present a general framework—improved prediction of miRNA-disease associations (IMDN)—based on matrix completion with network regularization to discover potential disease-related miRNAs. The success of adopting matrix factorization is demonstrated by its excellent performance in recommender systems. This approach considers a miRNA network as additional implicit feedback and makes predictions for disease associations relevant to a given miRNA based on its direct neighbors. Our experimental results demonstrate that IMDN achieved excellent performance with reliable area under the receiver operating characteristic (ROC) area under the curve (AUC) values of 0.9162 and 0.8965 in the frameworks of global and local leave-one-out cross-validations (LOOCV), respectively. Further, case studies demonstrated that our method can not only validate true miRNA-disease associations but also suggest novel disease-related miRNA candidates.

Graph regularized L2,1-nonnegative matrix factorization for miRNA-disease association prediction

BackgroundThe aberrant expression of microRNAs is closely connected to the occurrence and development of a great deal of human diseases. To study human diseases, numerous effective computational models that are valuable and meaningful have been presented by researchers.ResultsHere, we present a computational framework based on graph Laplacian regularized L2, 1-nonnegative matrix factorization (GRL2, 1-NMF) for inferring possible human disease-connected miRNAs. First, manually validated disease-connected microRNAs were integrated, and microRNA functional similarity information along with two kinds of disease semantic similarities were calculated. Next, we measured Gaussian interaction profile (GIP) kernel similarities for both diseases and microRNAs. Then, we adopted a preprocessing step, namely, weighted K nearest known neighbours (WKNKN), to decrease the sparsity of the miRNA-disease association matrix network. Finally, the GRL2,1-NMF framework was used to predict links between microRNAs and diseases.ConclusionsThe new method (GRL2, 1-NMF) achieved AUC values of 0.9280 and 0.9276 in global leave-one-out cross validation (global LOOCV) and five-fold cross validation (5-CV), respectively, showing that GRL2, 1-NMF can powerfully discover potential disease-related miRNAs, even if there is no known associated disease.

Identifying Potential miRNAs-Disease Associations With Probability Matrix Factorization.

In recent years, miRNAs have been verified to play an irreplaceable role in biological processes associated with human disease. Discovering potential disease-related miRNAs helps explain the underlying pathogenesis of the disease at the molecular level. Given the high cost and labor intensity of biological experiments, computational predictions will be an indispensable alternative. Therefore, we design a new model called probability matrix factorization (PMFMDA). Specifically, we first integrate miRNA and disease similarity. Next, the known association matrix and integrated similarity matrix are utilized to construct a probability matrix factorization algorithm to identify potentially relevant miRNAs for disease. We find that PMFMDA achieves reliable performance in the frameworks of global leave-one-out cross validation (LOOCV) and 5-fold cross validation (AUCs are 0.9237 and 0.9187, respectively) in the HMDD (V2.0) dataset, significantly outperforming a few state-of-the-art methods including CMFMDA, IMCMDA, NCPMDA, RLSMDA, and RWRMDA. In addition, case studies show that PMFMDA has good predictive performance for new associations, and the evidence can be identified by literature mining.

Predicting miRNA-Disease Associations by Incorporating Projections in Low-Dimensional Space and Local Topological Information.

Predicting the potential microRNA (miRNA) candidates associated with a disease helps in exploring the mechanisms of disease development. Most recent approaches have utilized heterogeneous information about miRNAs and diseases, including miRNA similarities, disease similarities, and miRNA-disease associations. However, these methods do not utilize the projections of miRNAs and diseases in a low-dimensional space. Thus, it is necessary to develop a method that can utilize the effective information in the low-dimensional space to predict potential disease-related miRNA candidates. We proposed a method based on non-negative matrix factorization, named DMAPred, to predict potential miRNA-disease associations. DMAPred exploits the similarities and associations of diseases and miRNAs, and it integrates local topological information of the miRNA network. The likelihood that a miRNA is associated with a disease also depends on their projections in low-dimensional space. Therefore, we project miRNAs and diseases into low-dimensional feature space to yield their low-dimensional and dense feature representations. Moreover, the sparse characteristic of miRNA-disease associations was introduced to make our predictive model more credible. DMAPred achieved superior performance for 15 well-characterized diseases with AUCs (area under the receiver operating characteristic curve) ranging from 0.860 to 0.973 and AUPRs (area under the precision-recall curve) ranging from 0.118 to 0.761. In addition, case studies on breast, prostatic, and lung neoplasms demonstrated the ability of DMAPred to discover potential disease-related miRNAs.

Predicting microRNA‐disease association based on microRNA structural and functional similarity network

BackgroundIncreasing evidences indicate that microRNAs (miRNAs) are functionally related to the development and progression of various human diseases. Inferring disease‐related miRNAs can be helpful in promoting disease biomarker detection for the treatment, diagnosis, and prevention of complex diseases.MethodsTo improve the prediction accuracy of miRNA‐disease association and capture more potential disease‐related miRNAs, we constructed a precise miRNA global similarity network (MSFSN) via calculating the miRNA similarity based on secondary structures, families, and functions.ResultsWe tested the network on the classical algorithms: WBSMDA and RWRMDA through the method of leave‐one‐out cross‐validation. Eventually, AUCs of 0.8212 and 0.9657 are obtained, respectively. Also, the proposed MSFSN is applied to three cancers for breast neoplasms, hepatocellular carcinoma, and prostate neoplasms. Consequently, 82%, 76%, and 82% of the top 50 potential miRNAs for these diseases are respectively validated by the miRNA‐disease associations database miR2Disease and oncomiRDB.ConclusionTherefore, MSFSN provides a novel miRNA similarity network combining precise function network with global structure network of miRNAs to predict the associations between miRNAs and diseases in various models.

Potential miRNA-disease association prediction based on kernelized Bayesian matrix factorization

Many biological experimental studies have confirmed that microRNAs (miRNAs) play a significant role in human complex diseases. Exploring miRNA-disease associations could be conducive to understanding disease pathogenesis at the molecular level and developing disease diagnostic biomarkers. However, since conducting traditional experiments is a costly and time-consuming way, plenty of computational models have been proposed to predict miRNA-disease associations. In this study, we presented a neoteric Bayesian model (KBMFMDA) that combines kernel-based nonlinear dimensionality reduction, matrix factorization and binary classification. The main idea of KBMFMDA is to project miRNAs and diseases into a unified subspace and estimate the association network in that subspace. KBMFMDA obtained the AUCs of 0.9132, 0.8708, 0.9008±0.0044 in global and local leave-one-out and five-fold cross validation. Moreover, KBMFMDA was applied to three important human cancers in three different kinds of case studies and most of the top 50 potential disease-related miRNAs were confirmed by many experimental reports.

FCMDAP: using miRNA family and cluster information to improve the prediction accuracy of disease related miRNAs

BackgroundBiological experiments have confirmed the association between miRNAs and various diseases. However, such experiments are costly and time consuming. Computational methods help select potential disease-related miRNAs to improve the efficiency of biological experiments.MethodsIn this work, we develop a novel method using multiple types of data to calculate miRNA and disease similarity based on mutual information, and add miRNA family and cluster information to predict human disease-related miRNAs (FCMDAP). This method not only depends on known miRNA-diseases associations but also accurately measures miRNA and disease similarity and resolves the problem of overestimation. FCMDAP uses the k most similar neighbor recommendation algorithm to predict the association score between miRNA and disease. Information about miRNA cluster is also used to improve prediction accuracy.ResultFCMDAP achieves an average AUC of 0.9165 based on leave-one-out cross validation. Results confirm the 100, 98 and 96% of the top 50 predicted miRNAs reported in case studies on colorectal, lung, and pancreatic neoplasms. FCMDAP also exhibits satisfactory performance in predicting diseases without any related miRNAs and miRNAs without any related diseases.ConclusionsIn this study, we present a computational method FCMDAP to improve the prediction accuracy of disease related miRNAs. FCMDAP could be an effective tool for further biological experiments.

A Novel Computational Method for the Identification of Potential miRNA-Disease Association Based on Symmetric Non-negative Matrix Factorization and Kronecker Regularized Least Square.

Increasing evidence has indicated that microRNAs (miRNAs) are associated with numerous human diseases. Studying the associations between miRNAs and diseases contributes to the exploration of effective diagnostic and treatment approaches for diseases. Unfortunately, the use of biological experiments to reveal the potential associations between miRNAs and diseases is time consuming and costly. Therefore, it is very necessary to use simple and efficient calculation models to predict potential disease-related miRNAs. Considering the limitations of other previous methods, we proposed a novel computational model of Symmetric Nonnegative Matrix Factorization for MiRNA-Disease Association prediction (SNMFMDA) to reveal the relation of miRNA-disease pairs. SNMFMDA could be applied to predict miRNAs associated with new diseases. Compared to the direct use of the integrated similarity in previous computational models, the integrated similarity need to be interpolated by symmetric non-negative matrix factorization (SymNMF) before application in SNMFMDA, and the relevant probability of disease-miRNA was obtained mainly through Kronecker regularized least square (KronRLS) method in our model. What's more, the AUC of global leave-one-out cross validation (LOOCV) reached 0.9007, and the AUC based on local LOOCV was 0.8426. Besides, the mean and the standard deviation of AUCs achieved 0.8830 and 0.0017 respectively in 5-fold cross validation. All of the above results demonstrated the superior prediction performance of SNMFMDA. We also conducted three different case studies on Esophageal Neoplasms, Breast Neoplasms and Lung Neoplasms, and 49, 49, and 48 of the top 50 of their predicted miRNAs respectively were confirmed by databases or related literatures. It could be expected that SNMFMDA would be a model with the ability to predict disease-related miRNAs efficiently and accurately.

MicroRNAs and complex diseases: from experimental results to computational models.

Plenty of microRNAs (miRNAs) were discovered at a rapid pace in plants, green algae, viruses and animals. As one of the most important components in the cell, miRNAs play a growing important role in various essential and important biological processes. For the recent few decades, amounts of experimental methods and computational models have been designed and implemented to identify novel miRNA-disease associations. In this review, the functions of miRNAs, miRNA-target interactions, miRNA-disease associations and some important publicly available miRNA-related databases were discussed in detail. Specially, considering the important fact that an increasing number of miRNA-disease associations have been experimentally confirmed, we selected five important miRNA-related human diseases and five crucial disease-related miRNAs and provided corresponding introductions. Identifying disease-related miRNAs has become an important goal of biomedical research, which will accelerate the understanding of disease pathogenesis at the molecular level and molecular tools design for disease diagnosis, treatment and prevention. Computational models have become an important means for novel miRNA-disease association identification, which could select the most promising miRNA-disease pairs for experimental validation and significantly reduce the time and cost of the biological experiments. Here, we reviewed 20 state-of-the-art computational models of predicting miRNA-disease associations from different perspectives. Finally, we summarized four important factors for the difficulties of predicting potential disease-related miRNAs, the framework of constructing powerful computational models to predict potential miRNA-disease associations including five feasible and important research schemas, and future directions for further development of computational models.

A novel method for identifying potential disease-related miRNAs via a disease-miRNA-target heterogeneous network.

MicroRNAs (miRNAs), as a kind of important small endogenous single-stranded non-coding RNA, play critical roles in a large number of human diseases. However, the currently known experimental verifications of the disease-miRNA associations are still rare and experimental identification is time-consuming and labor-intensive. Accordingly, identifying potential disease-related miRNAs to help people understand the pathogenesis of complex diseases has become a hot topic. In this study, we take advantage of known disease-miRNA associations combined with a large number of experimentally validated miRNA-target associations, and further develop a novel disease-miRNA-target heterogeneous network for identifying disease-related miRNAs. The leave-one-out cross validation experiment and several statistical measures demonstrate that our method can effectively identify potential disease-related miRNAs. Furthermore, the good predictive performance of 15 common diseases and the manually confirmed analyses of the top 30 candidates of hepatocellular carcinoma, ovarian neoplasms and breast neoplasms further provide convincing evidence of the practical ability of our method. The source code implemented by our method is freely available at: .

Inferring microRNA-disease associations by random walk on a heterogeneous network with multiple data sources.

Since the discovery of the regulatory function of microRNA (miRNA), increased attention has focused on identifying the relationship between miRNA and disease. It has been suggested that computational method are an efficient way to identify potential disease-related miRNAs for further confirmation using biological experiments. In this paper, we first highlighted three limitations commonly associated with previous computational methods. To resolve these limitations, we established disease similarity subnetwork and miRNA similarity subnetwork by integrating multiple data sources, where the disease similarity is composed of disease semantic similarity and disease functional similarity, and the miRNA similarity is calculated using the miRNA-target gene and miRNA-lncRNA (long non-coding RNA) associations. Then, a heterogeneous network was constructed by connecting the disease similarity subnetwork and the miRNA similarity subnetwork using the known miRNA-disease associations. We extended random walk with restart to predict miRNA-disease associations in the heterogeneous network. The leave-one-out cross-validation achieved an average area under the curve (AUC) of 0:8049 across 341 diseases and 476 miRNAs. For five-fold cross-validation, our method achieved an AUC from 0:7970 to 0:9249 for 15 human diseases. Case studies further demonstrated the feasibility of our method to discover potential miRNA-disease associations. An online service for prediction is freely available at http://ifmda.aliapp.com.