Inferring functional miRNA-mRNA regulatory modules in epithelial-mesenchymal transition with a probabilistic topic model

Kunming University of Science and Technology, Kunming, China.
Computers in Biology and Medicine (Impact Factor: 1.24). 01/2012; 42(4):428-37. DOI: 10.1016/j.compbiomed.2011.12.011
Source: PubMed


MicroRNAs (miRNAs) play important roles in gene regulatory networks. In this paper, we propose a probabilistic topic model to infer regulatory networks of miRNAs and their target mRNAs for specific biological conditions at the post-transcriptional level, so-called functional miRNA-mRNA regulatory modules (FMRMs). The probabilistic model used in this paper can effectively capture the relationship between miRNAs and mRNAs in specific cellular conditions. Furthermore, the proposed method identifies negatively and positively correlated miRNA-mRNA pairs which are associated with epithelial, mesenchymal, and other condition in EMT (epithelial-mesenchymal transition) data set, respectively. Results on EMT data sets show that the inferred FMRMs can potentially construct the biological chain of 'miRNA→mRNA→condition' at the post-transcriptional level.

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Available from: Junpeng Zhang, Jul 25, 2014
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    • "The discovery of MRMs has demonstrated that using both sequence information and expression profiles can produce more accurate predictions. Attempts have also been made to infer functional miRNA–mRNA regulatory modules (FMRMs), which are regulatory networks of miRNAs and mRNAs for specific biological conditions [19] [20] [21] [22] [23] [24] [25] [26]. The identified FMRMs give insights into biological processes, functional regulatory interactions of many diseases and gene target therapy. "
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    ABSTRACT: Discovering the regulatory relationships between microRNAs (miRNAs) and mRNAs is an important problem that interests many biologists and medical researchers. A number of computational methods have been proposed to infer miRNA-mRNA regulatory relationships, and are mostly based on the statistical associations between miRNAs and mRNAs discovered in observational data. The miRNA-mRNA regulatory relationships identified by these methods can be both direct and indirect regulations. However, differentiating direct regulatory relationships from indirect ones is important for biologists in experimental designs. In this paper, we present a causal discovery based framework (called DirectTarget) to infer direct miRNA-mRNA causal regulatory relationships in heterogeneous data, including expression profiles of miRNAs and mRNAs, and miRNA target information. DirectTarget is applied to the Epithelial to Mesenchymal Transition (EMT) datasets. The validation by experimentally confirmed target databases suggests that the proposed method can effectively identify direct miRNA-mRNA regulatory relationships. To explore the upstream regulators of miRNA regulation, we further identify the causal feedforward patterns (CFFPs) of TF-miRNA-mRNA to provide insights into the miRNA regulation in EMT. DirectTarget has the potential to be applied to other datasets to elucidate the direct miRNA-mRNA causal regulatory relationships and to explore the regulatory patterns.
    Journal of Biomedical Informatics 08/2014; 52. DOI:10.1016/j.jbi.2014.08.005 · 2.19 Impact Factor
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    ABSTRACT: MicroRNAs (miRNAs), a class of endogenous small noncoding RNAs, mediate posttranscriptional regulation of protein-coding genes by binding chiefly to the 3' untranslated region of target mRNAs, leading to translational inhibition, mRNA destabilization or degradation. A single miRNA concurrently downregulates hundreds of target mRNAs designated "targetome", and thereby fine-tunes gene expression involved in diverse cellular functions, such as development, differentiation, proliferation, apoptosis and metabolism. Recently, we characterized the molecular network of the whole human miRNA targetome by using bioinformatics tools for analyzing molecular interactions on the comprehensive knowledgebase. We found that the miRNA targetome regulated by an individual miRNA generally constitutes the biological network of functionally-associated molecules in human cells, closely linked to pathological events involved in cancers and neurodegenerative diseases. We also identified a collaborative regulation of gene expression by transcription factors and miRNAs in cancer-associated miRNA targetome networks. This review focuses on the workflow of molecular network analysis of miRNA targetome in silico. We applied the workflow to two representative datasets, composed of miRNA expression profiling of adult T cell leukemia (ATL) and Alzheimer's disease (AD), retrieved from Gene Expression Omnibus (GEO) repository. The results supported the view that miRNAs act as a central regulator of both oncogenesis and neurodegeneration.
    BioData Mining 10/2012; 5(1):17. DOI:10.1186/1756-0381-5-17 · 2.02 Impact Factor