miRNA-disease Interactions Research Articles

DAE-CFR: detecting microRNA-disease associations using deep autoencoder and combined feature representation

BackgroundMicroRNA (miRNA) has been shown to play a key role in the occurrence and progression of diseases, making uncovering miRNA-disease associations vital for disease prevention and therapy. However, traditional laboratory methods for detecting these associations are slow, strenuous, expensive, and uncertain. Although numerous advanced algorithms have emerged, it is still a challenge to develop more effective methods to explore underlying miRNA-disease associations.ResultsIn the study, we designed a novel approach on the basis of deep autoencoder and combined feature representation (DAE-CFR) to predict possible miRNA-disease associations. We began by creating integrated similarity matrices of miRNAs and diseases, performing a logistic function transformation, balancing positive and negative samples with k-means clustering, and constructing training samples. Then, deep autoencoder was used to extract low-dimensional feature from two kinds of feature representations for miRNAs and diseases, namely, original association information-based and similarity information-based. Next, we combined the resulting features for each miRNA-disease pair and used a logistic regression (LR) classifier to infer all unknown miRNA-disease interactions. Under five and tenfold cross-validation (CV) frameworks, DAE-CFR not only outperformed six popular algorithms and nine classifiers, but also demonstrated superior performance on an additional dataset. Furthermore, case studies on three diseases (myocardial infarction, hypertension and stroke) confirmed the validity of DAE-CFR in practice.ConclusionsDAE-CFR achieved outstanding performance in predicting miRNA-disease associations and can provide evidence to inform biological experiments and clinical therapy.

Clinical and biological significance of circulating miRNAs in chronic pancreatitis patients undergoing total pancreatectomy with islet autotransplantation.

Specific microRNAs (miRNAs) were elevated in chronic pancreatitis (CP) patients during islet infusion after total pancreatectomy (TPIAT). We aimed to identify circulating miRNA signatures of pancreatic damage, predict miRNA-mRNA networks to identify potential links to CP pathogenesis and identify islet isolation and transplantation functional outcomes. Small RNA sequencing was performed to identify distinct circulating miRNA signatures in CP. Plasma miRNAs were measured using miRCURY LNA SYBR green quantitative real-time polymerase chain reaction assays. Correlation analyses were performed using R software. The miRNA target and disease interactions were determined using miRNet and the miRNA enrichment and annotation tool. Alterations were found in circulating miRNAs in CP patients compared to healthy controls. Further studies were conducted on 12 circulating miRNAs enriched in the pancreas, other tissues and other diseases including cancer and fibrosis. Approximately 2888 mRNAs in the pancreas were their targets, demonstrating interactions with 76 small molecules. Three miRNAs exhibited interactions with morphine and five exhibited interactions with glucose. The miRNA panel targeted 22 genes associated with pancreatitis. The islet-specific, acinar cell-specific and liver-specific miRNAs were elevated at 6h after islet infusion and returned to baseline levels 3 months after TPIAT. Circulating levels of miRNAs returned to pre-transplant levels 1-year post-transplant. Circulating miRNAs measured before and 6h after islet infusion were directly or inversely associated with metabolic outcomes at 3 and 6 months post-transplant. miRNAs may contribute to CP pathogenesis, and elevated circulating levels may be specific to pancreatic inflammation and fibrosis, warranting further investigation.

KATZNCP: a miRNA–disease association prediction model integrating KATZ algorithm and network consistency projection

BackgroundClinical studies have shown that miRNAs are closely related to human health. The study of potential associations between miRNAs and diseases will contribute to a profound understanding of the mechanism of disease development, as well as human disease prevention and treatment. MiRNA–disease associations predicted by computational methods are the best complement to biological experiments.ResultsIn this research, a federated computational model KATZNCP was proposed on the basis of the KATZ algorithm and network consistency projection to infer the potential miRNA–disease associations. In KATZNCP, a heterogeneous network was initially constructed by integrating the known miRNA–disease association, integrated miRNA similarities, and integrated disease similarities; then, the KATZ algorithm was implemented in the heterogeneous network to obtain the estimated miRNA–disease prediction scores. Finally, the precise scores were obtained by the network consistency projection method as the final prediction results. KATZNCP achieved the reliable predictive performance in leave-one-out cross-validation (LOOCV) with an AUC value of 0.9325, which was better than the state-of-the-art comparable algorithms. Furthermore, case studies of lung neoplasms and esophageal neoplasms demonstrated the excellent predictive performance of KATZNCP.ConclusionA new computational model KATZNCP was proposed for predicting potential miRNA–drug associations based on KATZ and network consistency projections, which can effectively predict the potential miRNA–disease interactions. Therefore, KATZNCP can be used to provide guidance for future experiments.

Predicting miRNA-Disease Associations via Combining Probability Matrix Feature Decomposition With Neighbor Learning.

Predicting the associations of miRNAs and diseases may uncover the causation of various diseases. Many methods are emerging to tackle the sparse and unbalanced disease related miRNA prediction. Here, we propose a Probabilistic matrix decomposition combined with neighbor learning to identify MiRNA-Disease Associations utilizing heterogeneous data(PMDA). First, we build similarity networks for diseases and miRNAs, respectively, by integrating semantic information and functional interactions. Second, we construct a neighbor learning model in which the neighbor information of individual miRNA or disease is utilized to enhance the association relationship to tackle the spare problem. Third, we predict the potential association between miRNAs and diseases via probability matrix decomposition. The experimental results show that PMDA is superior to other five methods in sparse and unbalanced data. The case study shows that the new miRNA-disease interactions predicted by the PMDA are effective and the performance of the PMDA is superior to other methods.

Combined embedding model for MiRNA-disease association prediction

BackgroundCumulative evidence from biological experiments has confirmed that miRNAs have significant roles to diagnose and treat complex diseases. However, traditional medical experiments have limitations in time-consuming and high cost so that they fail to find the unconfirmed miRNA and disease interactions. Thus, discovering potential miRNA-disease associations will make a contribution to the decrease of the pathogenesis of diseases and benefit disease therapy. Although, existing methods using different computational algorithms have favorable performances to search for the potential miRNA-disease interactions. We still need to do some work to improve experimental results.ResultsWe present a novel combined embedding model to predict MiRNA-disease associations (CEMDA) in this article. The combined embedding information of miRNA and disease is composed of pair embedding and node embedding. Compared with the previous heterogeneous network methods that are merely node-centric to simply compute the similarity of miRNA and disease, our method fuses pair embedding to pay more attention to capturing the features behind the relative information, which models the fine-grained pairwise relationship better than the previous case when each node only has a single embedding. First, we construct the heterogeneous network from supported miRNA-disease pairs, disease semantic similarity and miRNA functional similarity. Given by the above heterogeneous network, we find all the associated context paths of each confirmed miRNA and disease. Meta-paths are linked by nodes and then input to the gate recurrent unit (GRU) to directly learn more accurate similarity measures between miRNA and disease. Here, the multi-head attention mechanism is used to weight the hidden state of each meta-path, and the similarity information transmission mechanism in a meta-path of miRNA and disease is obtained through multiple network layers. Second, pair embedding of miRNA and disease is fed to the multi-layer perceptron (MLP), which focuses on more important segments in pairwise relationship. Finally, we combine meta-path based node embedding and pair embedding with the cost function to learn and predict miRNA-disease association. The source code and data sets that verify the results of our research are shown at https://github.com/liubailong/CEMDA.ConclusionsThe performance of CEMDA in the leave-one-out cross validation and fivefold cross validation are 93.16% and 92.03%, respectively. It denotes that compared with other methods, CEMDA accomplishes superior performance. Three cases with lung cancers, breast cancers, prostate cancers and pancreatic cancers show that 48,50,50 and 50 out of the top 50 miRNAs, which are confirmed in HDMM V2.0. Thus, this further identifies the feasibility and effectiveness of our method.

Prediction of miRNA-Disease Association Using Deep Collaborative Filtering.

The existing studies have shown that miRNAs are related to human diseases by regulating gene expression. Identifying miRNA association with diseases will contribute to diagnosis, treatment, and prognosis of diseases. The experimental identification of miRNA-disease associations is time-consuming, tremendously expensive, and of high-failure rate. In recent years, many researchers predicted potential associations between miRNAs and diseases by computational approaches. In this paper, we proposed a novel method using deep collaborative filtering called DCFMDA to predict miRNA-disease potential associations. To improve prediction performance, we integrated neural network matrix factorization (NNMF) and multilayer perceptron (MLP) in a deep collaborative filtering framework. We utilized known miRNA-disease associations to capture miRNA-disease interaction features by NNMF and utilized miRNA similarity and disease similarity to extract miRNA feature vector and disease feature vector, respectively, by MLP. At last, we merged outputs of the NNMF and MLP to obtain the prediction matrix. The experimental results indicate that compared with other existing computational methods, our method can achieve the AUC of 0.9466 based on 10-fold cross-validation. In addition, case studies show that the DCFMDA can effectively predict candidate miRNAs for breast neoplasms, colon neoplasms, kidney neoplasms, leukemia, and lymphoma.

Predicting MiRNA-disease associations by multiple meta-paths fusion graph embedding model

BackgroundMany studies prove that miRNAs have significant roles in diagnosing and treating complex human diseases. However, conventional biological experiments are too costly and time-consuming to identify unconfirmed miRNA-disease associations. Thus, computational models predicting unidentified miRNA-disease pairs in an efficient way are becoming promising research topics. Although existing methods have performed well to reveal unidentified miRNA-disease associations, more work is still needed to improve prediction performance.ResultsIn this work, we present a novel multiple meta-paths fusion graph embedding model to predict unidentified miRNA-disease associations (M2GMDA). Our method takes full advantage of the complex structure and rich semantic information of miRNA-disease interactions in a self-learning way. First, a miRNA-disease heterogeneous network was derived from verified miRNA-disease pairs, miRNA similarity and disease similarity.All meta-path instances connecting miRNAs with diseases were extracted to describe intrinsic information about miRNA-disease interactions. Then, we developed a graph embedding model to predict miRNA-disease associations. The model is composed of linear transformations of miRNAs and diseases, the means encoder of a single meta-path instance, the attention-aware encoder of meta-path type and attention-aware multiple meta-path fusion. We innovatively integrated meta-path instances, meta-path based neighbours, intermediate nodes in meta-paths and more information to strengthen the prediction in our model. In particular, distinct contributions of different meta-path instances and meta-path types were combined with attention mechanisms. The data sets and source code that support the findings of this study are available at https://github.com/dangdangzhang/M2GMDA.ConclusionsM2GMDA achieved AUCs of 0.9323 and 0.9182 in global leave-one-out cross validation and fivefold cross validation with HDMM V2.0. The results showed that our method outperforms other prediction methods. Three kinds of case studies with lung neoplasms, breast neoplasms, prostate neoplasms, pancreatic neoplasms, lymphoma and colorectal neoplasms demonstrated that 47, 50, 49, 48, 50 and 50 out of the top 50 candidate miRNAs predicted by M2GMDA were validated by biological experiments. Therefore, it further confirms the prediction performance of our method.

Identifying Potential miRNA-Disease Associations Based on an Improved Manifold Learning Framework

Adequate evidence has shown that miRNA-disease interactions are strongly involved in the pathological processes of complex human diseases. However, it is commonly time-consuming and labor-intensive to utilize laboratory biological experiments to reveal unknown miRNA-disease pairs. Since the previously proposed calculation model has more or fewer deficiencies, we developed the semi-supervised method called Hessian Regularized Non-negative Matrix Factorization Method for miRNA-disease Association prediction (HRNMFMDA). This model introduced Hessian regularization into the NMF framework to preserve the local manifold information and increased an $l_{2,1}$ -norm penalty term to ensure the feature selection of the coding matrix and an approximate orthogonal constraint to obtain discriminative information. In the model performance evaluation, HRNMFMDA outperformed eight existing models, achieving AUC values of 0.9074, 0.8618, and 0.9044+/-0.0080 in the global leave-one-out cross-validation (LOOCV), local LOOCV and 5-fold cross-validation, respectively. In addition, we applied HRNMFMDA to several high-incidence human carcinomas via three kinds of case studies. Almost all predicted miRNAs were confirmed by external databases derived from experimental literature. Therefore, the conclusion can be drawn that HRNMFMDA is reliable for revealing uncovered miRNA-disease pairs.

IMIPMF: Inferring miRNA-disease interactions using probabilistic matrix factorization.

Recently, increasing evidence have reported that microRNAs (miRNAs) play key roles in a variety of biological processes. Therefore, the identification of novel miRNA-disease associations can shed new light on disease etiology and pathogenesis. Till now, various computational methods have been proposed to predict potential miRNA-disease associations by reducing the experimental costs and time consumption. However, most existing methods are highly dependent on known miRNA-disease associations. Therefore, the prediction of new miRNAs (i.e., miRNAs without known associated diseases) and new diseases (i.e., diseases without known associated miRNAs) has become challenging. In this paper, we present IMIPMF, a novel method for predicting miRNA-disease associations using probabilistic matrix factorization (PMF), which is a machine learning technique that is widely used in recommender systems. Predicting the rating scores that a user may assign to each item in a recommender system is analogous to predicting miRNA-disease associations. By applying PMF, our model not only identifies novel miRNA-disease associations, but also overcomes the common problem of incompatibility with miRNAs without any known associated disease, which was a limitation of most previous computational methods. We demonstrated that our proposed model achieved a high performance with a reliable AUC value of 0.891 by performing 5-fold cross-validation. Overall, IMIPMF is a high-performance machine-learning-based model for predicting miRNA-disease associations, although it only considers known miRNA-disease associations and miRNA expression data.

MiRNA-disease interaction prediction based on kernel neighborhood similarity and multi-network bidirectional propagation

BackgroundStudies have shown that miRNAs are functionally associated with the development of many human diseases, but the roles of miRNAs in diseases and their underlying molecular mechanisms have not been fully understood. The research on miRNA-disease interaction has received more and more attention. Compared with the complexity and high cost of biological experiments, computational methods can rapidly and efficiently predict the potential miRNA-disease interaction and can be used as a beneficial supplement to experimental methods.ResultsIn this paper, we proposed a novel computational model of kernel neighborhood similarity and multi-network bidirectional propagation (KNMBP) for miRNA-disease interaction prediction, especially for new miRNAs and new diseases. First, we integrated multiple data sources of diseases and miRNAs, respectively, to construct a novel disease semantic similarity network and miRNA functional similarity network. Secondly, based on the modified miRNA-disease interactions, we use the kernel neighborhood similarity algorithm to calculate the disease kernel neighborhood similarity and the miRNA kernel neighborhood similarity. Finally, we utilize bidirectional propagation algorithm to predict the miRNA-disease interaction scores based on the integrated disease similarity network and miRNA similarity network. As a result, the AUC value of 5-fold cross validation for all interactions by KNMBP is 0.93126 based on the commonly used dataset, and the AUC values for all interactions, for all miRNAs, for all disease is 0.93795、0.86363、0.86937 based on another dataset extracted by ourselves, which are higher than other state-of-the-art methods. In addition, our model has good parameter robustness. The case study further demonstrated the predictive performance of the model for novel miRNA-disease interactions.ConclusionsOur KNMBP algorithm efficiently integrates multiple omics data from miRNAs and diseases to stably and efficiently predict potential miRNA-disease interactions. It is anticipated that KNMBP would be a useful tool in biomedical research.

Predicting miRNA-disease interaction based on recommend method

PurposeMicroRNAs (miRNAs) have been proved to be a significant type of non-coding RNAs related to various human diseases. This paper aims to identify the potential miRNA–disease interactions.Design/methodology/approachA computational framework, MDIRM is presented to predict miRNAs-disease interactions. Unlike traditional approaches, the miRNA function similarity is calculated by miRNA–disease interactions. The k-mean method is further used to cluster miRNA similarity network. For miRNAs in the same cluster, their similarities are enhanced, as the miRNAs from the same cluster may be reliable. Further, the potential miRNA–disease association is predicted by using recommend method.FindingsTo evaluate the performance of our model, the fivefold cross validation is implemented to compare with two state-of-the-art methods. The experimental results indicate that MDIRM achieves an AUC of 0.926, which outperforms other methods.Originality/valueThis paper proposes a novel computational method for miRNA–disease interaction prediction based on recommend method. Identifying the relationship between miRNAs and diseases not only helps us better understand the disease occurrence and mechanism through the perspective of miRNA but also promotes disease diagnosis and treatment.

Identifying miRNA‐disease association based on integrating miRNA topological similarity and functional similarity

BackgroundMicroRNAs (miRNAs) are a significant type of non‐coding RNAs, which usually were encoded by endogenous genes with about ~22 nt nucleotides. Accumulating biological experiments have shown that miRNAs have close associations with various human diseases. Although traditional experimental methods achieve great successes in miRNA‐disease interaction identification, these methods also have some limitations. Therefore, it is necessary to develop computational method to predict miRNA‐disease interactions.MethodsHere, we propose a computational framework (MDVSI) to predict interactions between miRNAs and diseases by integrating miRNA topological similarity and functional similarity. Firstly, the CosRA index is utilized to measure miRNA similarity based on network topological feature. Then, in order to enhance the reliability of miRNA similarity, the functional similarity and CosRA similarity are integrated based on linear weight method. Further, the potential miRNA‐disease associations are predicted by using recommendation method. In addition, in order to overcome limitation of recommendation method, for new disease, a new strategy is proposed to predict potential interactions between miRNAs and new disease based on disease functional similarity.ResultsTo evaluate the performance of different methods, we conduct ten‐fold cross validation and de novo test in experiment and compare MDVSI with two the‐state‐of‐art methods. The experimental result shows that MDVSI achieves an AUC of 0.91, which is at least 0.012 higher than other compared methods.ConclusionsIn summary, we propose a computational framework (MDSVI) for miRNA‐disease interaction prediction. The experiment results demonstrate that it outperforms other the‐state‐of‐the‐art methods. Case study shows that it can effectively identify potential miRNA‐disease interactions.

A Novel Computational Model for Predicting microRNA-Disease Associations Based on Heterogeneous Graph Convolutional Networks.

Identifying the interactions between disease and microRNA (miRNA) can accelerate drugs development, individualized diagnosis, and treatment for various human diseases. However, experimental methods are time-consuming and costly. So computational approaches to predict latent miRNA–disease interactions are eliciting increased attention. But most previous studies have mainly focused on designing complicated similarity-based methods to predict latent interactions between miRNAs and diseases. In this study, we propose a novel computational model, termed heterogeneous graph convolutional network for miRNA–disease associations (HGCNMDA), which is based on known human protein–protein interaction (PPI) and integrates four biological networks: miRNA–disease, miRNA–gene, disease–gene, and PPI network. HGCNMDA achieved reliable performance using leave-one-out cross-validation (LOOCV). HGCNMDA is then compared to three state-of-the-art algorithms based on five-fold cross-validation. HGCNMDA achieves an AUC of 0.9626 and an average precision of 0.9660, respectively, which is ahead of other competitive algorithms. We further analyze the top-10 unknown interactions between miRNA and disease. In summary, HGCNMDA is a useful computational model for predicting miRNA–disease interactions.

Towards a Comprehensive Understanding of miRNA Regulome and miRNA Interaction Networks

miRNAs are vital regulators of post transcriptional gene expression. Deregulation of miRNAs lead to susceptibility towards many diseases, especially cancers. Their complicated molecular mechanisms comprising of upstream transcriptions factors, downstream targets, functional and biological processes, and disease regulations are not fully comprehended yet. Hence, understanding the miRNA regulatory network comprehensively is pivotal to modulate its functions and develop miRNA therapeutics. At present, several independent databases and tools containing specific information about parts of a miRNA regulome exist in silo which prevents a holistic understanding of miRNA's molecular mechanism. Hence, integration of all scattered datasets in a cohesive manner in order to get an overarching understanding of the contributory influence and the effluence from the machinery of a miRNA regulome is critical. In this article, we present a case-report on miRegulome, a first comprehensive integrated knowledge base of miRNA regulome and miRNA interaction network analytic tools. miRegulome integrates the essential molecular modules of a miRNA regulome into a cohesive platform. We also discuss miRNA-disease interactions from miRegulome and devise graph theoretical strategies to analyze them. We also present a next-level design for an enhanced database repository for comprehensive data analysis collating diverse datasets related to miRNA biology; and present the need and challenges for the development of novel algorithms to predict new interactions between miRNAs, genes, transcription factors and diseases.

RWRMDA: predicting novel human microRNA–disease associations

Recently, more and more research has shown that microRNAs (miRNAs) play critical roles in the development and progression of various diseases, but it is not easy to predict potential human miRNA-disease associations from the vast amount of biological data. Computational methods for predicting potential disease-miRNA associations have gained a lot of attention based on their feasibility, guidance and effectiveness. Differing from traditional local network similarity measures, we adopted global network similarity measures and developed Random Walk with Restart for MiRNA-Disease Association (RWRMDA) to infer potential miRNA-disease interactions by implementing random walk on the miRNA-miRNA functional similarity network. We tested RWRMDA on 1616 known miRNA-disease associations based on leave-one-out cross-validation, and achieved an area under the ROC curve of 86.17%, which significantly improves previous methods. The method was also applied to three cancers for accuracy evaluation. As a result, 98% (Breast cancer), 74% (Colon cancer), and 88% (Lung cancer) of top 50 predicted miRNAs are confirmed by published experiments. These results suggest that RWRMDA will represent an important bioinformatics resource in biomedical research of both miRNAs and diseases.