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This article is part of the supplement: Italian Society of Bioinformatics (BITS): Annual Meeting 2012

Open Access Research

A Novel Biclustering Algorithm for the Discovery of Meaningful Biological Correlations between microRNAs and their Target Genes

Gianvito Pio1*, Michelangelo Ceci1*, Domenica D'Elia2, Corrado Loglisci1 and Donato Malerba1

Author Affiliations

1 Department of Computer Science, University of Bari "Aldo Moro", Via Orabona 4, 70125, Bari, Italy

2 CNR, Institute for Biomedical Technologies, Via Amendola 122/D, 70126, Bari, Italy

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BMC Bioinformatics 2013, 14(Suppl 7):S8  doi:10.1186/1471-2105-14-S7-S8

Published: 22 April 2013

Abstract

Background

microRNAs (miRNAs) are a class of small non-coding RNAs which have been recognized as ubiquitous post-transcriptional regulators. The analysis of interactions between different miRNAs and their target genes is necessary for the understanding of miRNAs' role in the control of cell life and death. In this paper we propose a novel data mining algorithm, called HOCCLUS2, specifically designed to bicluster miRNAs and target messenger RNAs (mRNAs) on the basis of their experimentally-verified and/or predicted interactions. Indeed, existing biclustering approaches, typically used to analyze gene expression data, fail when applied to miRNA:mRNA interactions since they usually do not extract possibly overlapping biclusters (miRNAs and their target genes may have multiple roles), extract a huge amount of biclusters (difficult to browse and rank on the basis of their importance) and work on similarities of feature values (do not limit the analysis to reliable interactions).

Results

To overcome these limitations, HOCCLUS2 i) extracts possibly overlapping biclusters, to catch multiple roles of both miRNAs and their target genes; ii) extracts hierarchically organized biclusters, to facilitate bicluster browsing and to distinguish between universe and pathway-specific miRNAs; iii) extracts highly cohesive biclusters, to consider only reliable interactions; iv) ranks biclusters according to the functional similarities, computed on the basis of Gene Ontology, to facilitate bicluster analysis.

Conclusions

Our results show that HOCCLUS2 is a valid tool to support biologists in the identification of context-specific miRNAs regulatory modules and in the detection of possibly unknown miRNAs target genes. Indeed, results prove that HOCCLUS2 is able to extract cohesiveness-preserving biclusters, when compared with competitive approaches, and statistically confirm (at a confidence level of 99%) that mRNAs which belong to the same biclusters are, on average, more functionally similar than mRNAs which belong to different biclusters. Finally, the hierarchy of biclusters provides useful insights to understand the intrinsic hierarchical organization of miRNAs and their potential multiple interactions on target genes.