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Open Access Highly Accessed Methodology article

REACTIN: Regulatory activity inference of transcription factors underlying human diseases with application to breast cancer

Mingzhu Zhu1, Chun-Chi Liu23 and Chao Cheng1456*

Author Affiliations

1 Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03755, USA

2 Institute of Genomics and Bioinformatics, National Chung Hsing University, Taichung, Taiwan

3 Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan

4 Institute for Quantitative Biomedical Sciences, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03766, USA

5 Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03766, USA

6 Department of Genetics, Institute for Quantitative Biomedical Sciences, Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03766, USA

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BMC Genomics 2013, 14:504  doi:10.1186/1471-2164-14-504

Published: 26 July 2013

Abstract

Background

Genetic alterations of transcription factors (TFs) have been implicated in the tumorigenesis of cancers. In many cancers, alteration of TFs results in aberrant activity of them without changing their gene expression level. Gene expression data from microarray or RNA-seq experiments can capture the expression change of genes, however, it is still challenge to reveal the activity change of TFs.

Results

Here we propose a method, called REACTIN (REgulatory ACTivity INference), which integrates TF binding data with gene expression data to identify TFs with significantly differential activity between disease and normal samples. REACTIN successfully detect differential activity of estrogen receptor (ER) between ER+ and ER- samples in 10 breast cancer datasets. When applied to compare tumor and normal breast samples, it reveals TFs that are critical for carcinogenesis of breast cancer. Moreover, Reaction can be utilized to identify transcriptional programs that are predictive to patient survival time of breast cancer patients.

Conclusions

REACTIN provides a useful tool to investigate regulatory programs underlying a biological process providing the related case and control gene expression data. Considering the enormous amount of cancer gene expression data and the increasingly accumulating ChIP-seq data, we expect wide application of REACTIN for revealing the regulatory mechanisms of various diseases.

Keywords:
Transcription factor; ChIP-seq; Gene expression