Dataset Information

PROmiRNA: a new miRNA promoter recognition method uncovers the complex regulation of intronic miRNAs.

ABSTRACT: The regulation of intragenic miRNAs by their own intronic promoters is one of the open problems of miRNA biogenesis. Here, we describe PROmiRNA, a new approach for miRNA promoter annotation based on a semi-supervised statistical model trained on deepCAGE data and sequence features. We validate our results with existing annotation, PolII occupancy data and read coverage from RNA-seq data. Compared to previous methods PROmiRNA increases the detection rate of intronic promoters by 30%, allowing us to perform a large-scale analysis of their genomic features, as well as elucidate their contribution to tissue-specific regulation. PROmiRNA can be downloaded from http://promirna.molgen.mpg.de.

SUBMITTER: Marsico A

PROVIDER: S-EPMC4053815 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

PROmiRNA: a new miRNA promoter recognition method uncovers the complex regulation of intronic miRNAs.

Marsico Annalisa A Huska Matthew R MR Lasserre Julia J Hu Haiyang H Vucicevic Dubravka D Musahl Anne A Orom Ulf U Vingron Martin M

Genome biology 20130816 8

The regulation of intragenic miRNAs by their own intronic promoters is one of the open problems of miRNA biogenesis. Here, we describe PROmiRNA, a new approach for miRNA promoter annotation based on a semi-supervised statistical model trained on deepCAGE data and sequence features. We validate our results with existing annotation, PolII occupancy data and read coverage from RNA-seq data. Compared to previous methods PROmiRNA increases the detection rate of intronic promoters by 30%, allowing us ...[more]

PMID: 23958307

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Project description:BackgroundMany classifiers 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 another method, and thus such markers always lack discriminative capability in the other data sets.MethodsIn 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 distinguishing 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.ResultsAfter 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.ConclusionsOne 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.

Dataset Information

PROmiRNA: a new miRNA promoter recognition method uncovers the complex regulation of intronic miRNAs.

Publications

PROmiRNA: a new miRNA promoter recognition method uncovers the complex regulation of intronic miRNAs.

Similar Datasets

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