Dataset Information

Uncover miRNA-Disease Association by Exploiting Global Network Similarity.

ABSTRACT: Identification of miRNA-disease association is a fundamental challenge in human health clinic. However, the known miRNA-disease associations are rare and experimental verification methods are expensive and time-consuming. Therefore, there is a strong incentive to develop computational methods. In this paper, we calculate the similarity score for each miRNAs pair by integrating miRNA functional similarity and miRNA family information. We use the disease phenotype similarity data to construct the disease similarity network. Then we introduce a new miRNA-disease association prediction method (NETwork Group Similarity, NetGS) to explore the global network similarity, capturing the relationship between the disease and other diseases, the similarity between the potential disease-related miRNA and other miRNAs. Finally based on the consistency of diffusion profiles we get the miRNA-disease association scores. NetGS is tested by the leave-one-out cross validation and achieves an AUC value of 0.8450, which improves the prediction accuracy. NetGS can also be applied to solve the new miRNA-disease association and obtain reliable accuracy. Moreover, we use NetGS to predict new causing miRNAs of three cancers including breast cancer, lung cancer and Hepatocellular cancer. And the top predictions have been confirmed in the online databases. The encouraging results indicate that NetGS might play an essential role for future scientific research.

SUBMITTER: Chen M

PROVIDER: S-EPMC5132253 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Uncover miRNA-Disease Association by Exploiting Global Network Similarity.

Chen Min M Lu Xingguo X Liao Bo B Li Zejun Z Cai Lijun L Gu Changlong C

PloS one 20161201 12

Identification of miRNA-disease association is a fundamental challenge in human health clinic. However, the known miRNA-disease associations are rare and experimental verification methods are expensive and time-consuming. Therefore, there is a strong incentive to develop computational methods. In this paper, we calculate the similarity score for each miRNAs pair by integrating miRNA functional similarity and miRNA family information. We use the disease phenotype similarity data to construct the ...[more]

PMID: 27907011

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Project description: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.

Project description:The molecular complexity of genetic diseases requires novel approaches to break it down into coherent biological modules. For this purpose, many disease network models have been created and analyzed. We highlight two of them, "the human diseases networks" (HDN) and "the orphan disease networks" (ODN). However, in these models, each single node represents one disease or an ambiguous group of diseases. In these cases, the notion of diseases as unique entities reduces the usefulness of network-based methods. We hypothesize that using the clinical features (pathophenotypes) to define pathophenotypic connections between disease-causing genes improve our understanding of the molecular events originated by genetic disturbances. For this, we have built a pathophenotypic similarity gene network (PSGN) and compared it with the unipartite projections (based on gene-to-gene edges) similar to those used in previous network models (HDN and ODN). Unlike these disease network models, the PSGN uses semantic similarities. This pathophenotypic similarity has been calculated by comparing pathophenotypic annotations of genes (human abnormalities of HPO terms) in the "Human Phenotype Ontology". The resulting network contains 1075 genes (nodes) and 26197 significant pathophenotypic similarities (edges). A global analysis of this network reveals: unnoticed pairs of genes showing significant pathophenotypic similarity, a biological meaningful re-arrangement of the pathological relationships between genes, correlations of biochemical interactions with higher similarity scores and functional biases in metabolic and essential genes toward the pathophenotypic specificity and the pleiotropy, respectively. Additionally, pathophenotypic similarities and metabolic interactions of genes associated with maple syrup urine disease (MSUD) have been used to merge into a coherent pathological module.Our results indicate that pathophenotypes contribute to identify underlying co-dependencies among disease-causing genes that are useful to describe disease modularity.

Project description:BACKGROUND:As regulators of gene expression, microRNAs (miRNAs) are increasingly recognized as critical biomarkers of human diseases. Till now, a series of computational methods have been proposed to predict new miRNA-disease associations based on similarity measurements. Different categories of features in miRNAs are applied in these methods for miRNA-miRNA similarity calculation. Benchmarking tests on these miRNA similarity measures are warranted to assess their effectiveness and robustness. RESULTS:In this study, 5 categories of features, i.e. miRNA sequences, miRNA expression profiles in cell-lines, miRNA expression profiles in tissues, gene ontology (GO) annotations of miRNA target genes and Medical Subject Heading (MeSH) terms of miRNA-associated diseases, are collected and similarity values between miRNAs are quantified based on these feature spaces, respectively. We systematically compare the 5 similarities from multi-statistical views. Furthermore, we adopt a rule-based inference method to test their performance on miRNA-disease association predictions with the similarity measurements. Comprehensive comparison is made based on leave-one-out cross-validations and a case study. Experimental results demonstrate that the similarity measurement using MeSH terms performs best among the 5 measurements. It should be noted that the other 4 measurements can also achieve reliable prediction performance. The best-performed similarity measurement is used for new miRNA-disease association predictions and the inferred results are released for further biomedical screening. CONCLUSIONS:Our study suggests that all the 5 features, even though some are restricted by data availability, are useful information for inferring novel miRNA-disease associations. However, biased prediction results might be produced in GO- and MeSH-based similarity measurements due to incomplete feature spaces. Similarity fusion may help produce more reliable prediction results. We expect that future studies will provide more detailed information into the 5 feature spaces and widen our understanding about disease pathogenesis.

Dataset Information

Uncover miRNA-Disease Association by Exploiting Global Network Similarity.

Publications

Uncover miRNA-Disease Association by Exploiting Global Network Similarity.

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