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ABBREVIATIONS ADT Androgen-Deprivation Therapy CRPC Castration Resistant Prostate Cancer ChIP-seq Chromatin Immunoprecipitation followed by Sequencing ENCODE The Encyclopedia of DNA Elements Project FACS Fluorescence-Activated Cell Sorting GEO Gene Expression Omnibus GSEA Gene Set Enrichment Analysis H3K4me1 Histone 3 Lysine 4 Mono-methylation H3K4me3 Histone 3 Lysine 4 Tri-methylation H3K36me3 Histone 3 Lysine 36 Tri-methylation H3K9ac Histone 3 Lysine 9 Acetylation H3K27me3 Histone 3 Lysine 27 Tri-methylation H3K9me3 Histone 3 Lysine 9 Tri-methylation NGS Next Generation Sequencing PCSC Prostate Cancer Stem Cell PSA Prostate Specific Antigen SVM Support Vector Machines TCGA The Cancer Genome Atlas FACILITIES and RESOURCES We have full access to high performance computer cluster in Dan L. Duncan Cancer Center, which is equipped with 26 computation nodes, including 18 nodes with two 4core AMD 2312 CPUs and 32GB memory each node, and 8 high performance nodes with two 6-core Intel Xeon 5690 CPUs and 96GB memory. These node share 30 TB hard disk storage with distributed backup system. We also have access to BlueBioU super computer in Rice University as secondary computation resource. The BlueBiou computer cluster contain 47 nodes with four 8-core POWER7 CPUs and 256GB memory each node, and share a total 474TB (217TB BlueBiou specific and 257 TB common) storage system. (http://www.rcsg.rice.edu/sharecore/bluebiou/) The Human Genome Sequencing Center (HGSC) at Baylor College of Medicine (BCM) will provide sequencing service for ChIP-seq. BCM-HGSC is equipped with Illumina Solexa Hiseq 2000 sequencing system for high throughput next generation sequencing. PUBLICATIONS 1. Yao J, Liu X, Sakuno T, Li W, Xi Y, Aravamudhan P, Joglekar A, Li W, Watanabe Y, He X: Plasticity and Epigenetic Inheritance of Centromere Specific Histone H3 (CENP-A) Containing-Nucleosome Positioning in the Fission Yeast. J Biol Chem. 2013; 288(26):19184-96. PMID: 23661703 2. Chen K, Xi Y, Pan X, Dent S, He X, Li W: DANPOS: Dynamic Analysis of Nucleosome Position and Occupancy by Sequencing. Genome Res. 2013; 23(2):341-51. PMID: 23193179 3. MF Barber*, Michishita E*, Xi Y*(joint first author), Tasselli L, Kioi M, Moqtaderi Z, Tennen RI, Paredes S, Young NL, Chen K, Struhl K, Garcia BA, Gozani O, Li W, Chua KF. SIRT7 links H3K18 deacetylation to maintenance of oncogenic transformation. Nature. 2012; 487(7405), 114–118. PMID: 22722849 4. Xiao R, Sun D, Dayers S, Xi Y, Li W, Moore D. The Estrogen Receptor Alpha Cistrome Defined by DamIP. Mol Endocrinol. 2012;26(2):349-357. PMID: 22207717 5. Klisch TJ*, Xi Y*(joint first author), Flora A, Wang L, Li W, Zoghbi HY. In vivo Atoh1 targetome reveals how a proneural transcription factor regulates cerebellar development. Proc Natl Acad Sci USA. 2011 108(8):3288-3293. PMID: 21300888 6. Xi Y*, Bock C*, Müller F, Sun D, Meissner A, Li W. RRBSMAP: A Fast, Accurate and User-friendly Alignment Tool for Reduced Representation Bisulfite Sequencing. Bioinformatics. 2012;28(3):430-432. PMID: 22155871 7. Challen G, Sun D, Jeong M, Luo M, Jelinek J, Berg J, Bock C, Vasanthakumar A, Gu H, Xi Y, Liang S, Lu Y, Darlington G, Meissner A, Issa J, Godley L, Li W, Goodell M. Dnmt3a is Essential for Hematopoietic Stem Cell Differentiation. Nat Genet. 2011; 44(1):23-31. PMID: 22138693 8. Xi Y*, Yao J*, Chen R, Li W, He X. Nucleosome fragility reveals novel functional states of chromatin and poises genes for activation. Genome Res. 2011; 21(5):718-724. PMID: 21363969 9. Xi Y, Li W. BSMAP: whole genome bisulfite sequence mapping program. BMC Bioinformatics. 2009; 10:232. PMID: 19635165 10. Kuo AJ, Cheung P, Chen K, Zee BM, Kioi M, Lauring J, Xi Y, Park BH, Shi X, Garcia BA, Li W, Gozani O. NSD2 Links Dimethylation of Histone H3 at Lysine 36 to Oncogenic Programming. Mol Cell. 2011; 44(4):609-620 11. Harris RA, Wang T, Coarfa C, Nagarajan RP, Hong C, Downey SL, Johnson BE, Fouse SD, Delaney A, Zhao Y, Olshen A, Ballinger T, Zhou X, Forsberg KJ, Gu J, Echipare L, O'Geen H, Lister R, Pelizzola M, Xi Y, Epstein CB, Bernstein BE, Hawkins RD, Ren B, Chung WY, Gu H, Bock C, Gnirke A, Zhang MQ, Haussler D, Ecker JR, Li W, Farnham PJ, Waterland RA, Meissner A, Marra MA, Hirst M, Milosavljevic A, Costello JF. Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications. Nat Biotechnol. 2010; 28(10):1097-1105. PMID: 20852635 12. Kim BJ, Li Y, Zhang J, Xi Y, Li Y, Yang T, Jung SY, Pan X, Chen R, Li W, Wang Y, Qin J. Genome-wide reinforcement of cohesin binding at pre-existing cohesin sites in response to ionizing radiation in human cells. J Biol Chem. 2010; 285(30):22784-22792. PMID: 20501661 13. Xi Y, de Ropp JS, Viant MR, Woodruff DL, Yu P. Improved identification of metabolites in complex mixtures using HSQC NMR spectroscopy. Anal Chim Acta. 2008; 614(2):127-133. PMID: 18420042 14. Xi Y, Rocke DM. Baseline correction for NMR spectroscopic metabolomics data analysis. BMC Bioinformatics. 2008; 9:324. PMID: 18664284 15. Xi Y, de Ropp J, Viant M, Woodruff D, Yu P. Automated screening for metabolites in complex mixtures using 2D COSY NMR spectroscopy. Metabolomics, 2006; 2(4): 221-233. INTELLECTUAL PROPERTY PLAN The results of the proposed study will be published in peered reviewed journals. The data processing pipeline, including the source code and manual, will be released for public usage without charges under the GNU General Public License version 3 (GPLv3) (http://www.gnu.org/licenses/agpl-3.0.html) DATA AND RESEARCH RESOURCE SHARING PLAN The ChIP-seq raw reads and processed data will be deposited to the NCBI Gene Expression Omnibus (GEO) database. (http://www.ncbi.nlm.nih.gov/geo/) We also plan to build a customized website to host the data, software, publications and analyses results of the proposed study for public access.