Dataset Information

MiRLAB: An R Based Dry Lab for Exploring miRNA-mRNA Regulatory Relationships.

ABSTRACT: microRNAs (miRNAs) are important gene regulators at post-transcriptional level, and inferring miRNA-mRNA regulatory relationships is a crucial problem. Consequently, several computational methods of predicting miRNA targets have been proposed using expression data with or without sequence based miRNA target information. A typical procedure for applying and evaluating such a method is i) collecting matched miRNA and mRNA expression profiles in a specific condition, e.g. a cancer dataset from The Cancer Genome Atlas (TCGA), ii) applying the new computational method to the selected dataset, iii) validating the predictions against knowledge from literature and third-party databases, and comparing the performance of the method with some existing methods. This procedure is time consuming given the time elapsed when collecting and processing data, repeating the work from existing methods, searching for knowledge from literature and third-party databases to validate the results, and comparing the results from different methods. The time consuming procedure prevents researchers from quickly testing new computational models, analysing new datasets, and selecting suitable methods for assisting with the experiment design. Here, we present an R package, miRLAB, for automating the procedure of inferring and validating miRNA-mRNA regulatory relationships. The package provides a complete set of pipelines for testing new methods and analysing new datasets. miRLAB includes a pipeline to obtain matched miRNA and mRNA expression datasets directly from TCGA, 12 benchmark computational methods for inferring miRNA-mRNA regulatory relationships, the functions for validating the predictions using experimentally validated miRNA target data and miRNA perturbation data, and the tools for comparing the results from different computational methods.

SUBMITTER: Le TD

PROVIDER: S-EPMC4696828 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

miRLAB: An R Based Dry Lab for Exploring miRNA-mRNA Regulatory Relationships.

Le Thuc Duy TD Zhang Junpeng J Liu Lin L Liu Huawen H Li Jiuyong J

PloS one 20151230 12

microRNAs (miRNAs) are important gene regulators at post-transcriptional level, and inferring miRNA-mRNA regulatory relationships is a crucial problem. Consequently, several computational methods of predicting miRNA targets have been proposed using expression data with or without sequence based miRNA target information. A typical procedure for applying and evaluating such a method is i) collecting matched miRNA and mRNA expression profiles in a specific condition, e.g. a cancer dataset from The ...[more]

PMID: 26716983

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Project description:BackgroundmicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level and they play an important role in various biological processes in the human body. Therefore, identifying their regulation mechanisms is essential for the diagnostics and therapeutics for a wide range of diseases. There have been a large number of researches which use gene expression profiles to resolve this problem. However, the current methods have their own limitations. Some of them only identify the correlation of miRNA and mRNA expression levels instead of the causal or regulatory relationships while others infer the causality but with a high computational complexity. To overcome these issues, in this study, we propose a method to identify miRNA-mRNA regulatory relationships in breast cancer using the invariant causal prediction. The key idea of invariant causal prediction is that the cause miRNAs of their target mRNAs are the ones which have persistent causal relationships with the target mRNAs across different environments.ResultsIn this research, we aim to find miRNA targets which are consistent across different breast cancer subtypes. Thus, first of all, we apply the Pam50 method to categorize BRCA samples into different "environment" groups based on different cancer subtypes. Then we use the invariant causal prediction method to find miRNA-mRNA regulatory relationships across subtypes. We validate the results with the miRNA-transfected experimental data and the results show that our method outperforms the state-of-the-art methods. In addition, we also integrate this new method with the Pearson correlation analysis method and Lasso in an ensemble method to take the advantages of these methods. We then validate the results of the ensemble method with the experimentally confirmed data and the ensemble method shows the best performance, even comparing to the proposed causal method.ConclusionsThis research found miRNA targets which are consistent across different breast cancer subtypes. Further functional enrichment analysis shows that miRNAs involved in the regulatory relationships predicated by the proposed methods tend to synergistically regulate target genes, indicating the usefulness of these methods, and the identified miRNA targets could be used in the design of wet-lab experiments to discover the causes of breast cancer.

Dataset Information

MiRLAB: An R Based Dry Lab for Exploring miRNA-mRNA Regulatory Relationships.

Publications

miRLAB: An R Based Dry Lab for Exploring miRNA-mRNA Regulatory Relationships.

Similar Datasets

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