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This article is part of the supplement: Selected articles from the IEEE International Conference on Bioinformatics and Biomedicine 2012: Bioinformatics

Open Access Research

Ensemble classifier based on context specific miRNA regulation modules: a new method for cancer outcome prediction

Xionghui Zhou1, Juan Liu1*, Xinghuo Ye1, Wei Wang1 and Jianghui Xiong2

Author Affiliations

1 School of Computer, Wuhan University, Wuhan, P.R. China

2 Bioinformatics Group and Data Coordination Centre, State Key Lab of Space Medicine Fundamentals and Application, China Astronaut Research and Training Centre, Beijing, P.R. China

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BMC Bioinformatics 2013, 14(Suppl 12):S6  doi:10.1186/1471-2105-14-S12-S6

Published: 24 September 2013

Abstract

Background

Many calssifiers which are constructed with chosen gene markers have been proposed to forecast the prognosis of patients who suffer from breast cancer. However, few of them has been applied in clinical practice because of the bad generalization, which results from the situation that markers selected by one method are very different from those obtained by anohter mothod, and thus such markers always lack discriminative capability in the other data sets.

Methods

In this work, a new ensemble classifier, on the basis of context specific miRNA regulation modules, has been proposed to forecast the metastasis risk of cancer sufferers. First, we defined all of the miRNAs which regulate the same context as a module that contains miRNAs and their regulating context, and applied the CoMi (Context-specific miRNA activity) score in order to illustrate a miRNA's effect which happened in a particular background; then the miRNA regulation modules with distinguising abilities were detected and each of them was responsible for building a weak classifier separately; at last, by using majority voting strategy, we integrated all weak classifiers to establish an ensembled one that was applied to forecast the prognosis of patients who suffer from cancer.

Results

After comparing, the results on the cohorts containing over 1,000 samples showed that the proposed ensemble classifier is superior to other three classifiers based on miRNA expression profiles, mRNA expression profiles and CoMi activity patterns respectively. Significantly, our method outperforms the representative works. Moreover, the detected modules from different data sets show great stability (with p-value of 6.40e-08). For investigating the biological significance of those selected modules, case studies have been done by us and the results suggested that our method do help to reveal latent mechanism in metastasis of breast cancer.

Conclusions

One context specific miRNA regulation module can uncover one critical biological process and its involved miRNAs that are related to the cancer outcome, and several modules together can help to study the biological mechanism in cancer metastasis, thus the classifer based on ensembling multiple classifers which were built with different context specific miRNA regulation modules has showed promising performances in terms with both prediction accuracy and generalization.