Epidaurus: aggregation and integration analysis of prostate cancer epigenome.
Integrative analyses of epigenetic data promise a deeper understanding of the epigenome. Epidaurus is a bioinformatics tool used to effectively reveal inter-dataset relevance and differences through data aggregation, integration and visualization. In this study, we demonstrated the utility of Epidaurus in validating hypotheses and generating novel biological insights. In particular, we described the use of Epidaurus to (i) integrate epigenetic data from prostate cancer cell lines to validate the activation function of EZH2 in castration-resistant prostate cancer and to (ii) study the mechanism of androgen receptor (AR) binding deregulation induced by the knockdown of FOXA1. We found that EZH2's noncanonical activation function was reaffirmed by its association with active histone markers and the lack of association with repressive markers. More importantly, we revealed that the binding of AR was selectively reprogramed to promoter regions, leading to the up-regulation of hundreds of cancer-associated genes including EGFR. The prebuilt epigenetic dataset from commonly used cell lines (LNCaP, VCaP, LNCaP-Abl, MCF7, GM12878, K562, HeLa-S3, A549, HePG2) makes Epidaurus a useful online resource for epigenetic research. As standalone software, Epidaurus is specifically designed to process user customized datasets with both efficiency and convenience.
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN 55905, USA.
Liguo
L
Wang
Department of Biochemistry and Molecular Biology, Mayo Clinic, MN 55905, USA.
Haojie
H
Huang
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN 55905, USA.
Gregory
G
Dougherty
Department of Biochemistry and Molecular Biology, Mayo Clinic, MN 55905, USA.
Yu
Y
Zhao
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN 55905, USA.
Asif
A
Hossain
Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN 55905, USA kocher.jeanpierre@mayo.edu.
Jean-Pierre A
JP
Kocher
D045744:Cell Line, Tumor; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics*; D011944:Receptors, Androgen / Q000378:metabolism; D012984:Software; D015534:Trans-Activators / Q000378:metabolism
C496499:FOXA1 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D011944:Receptors, Androgen; D015534:Trans-Activators; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2