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Biostatistics 2004 5(4):557-572; doi:10.1093/biostatistics/kxh008
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Biostatistics Vol. 5 No. 4 © Oxford University Press 2004; all rights reserved.

Circular binary segmentation for the analysis of array-based DNA copy number data

Adam B. Olshen and E. S. Venkatraman

Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA
olshena{at}mskcc.org

Robert Lucito and Michael Wigler

Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA

DNA sequence copy number is the number of copies of DNA at a region of a genome. Cancer progression often involves alterations in DNA copy number. Newly developed microarray technologies enable simultaneous measurement of copy number at thousands of sites in a genome. We have developed a modification of binary segmentation, which we call circular binary segmentation, to translate noisy intensity measurements into regions of equal copy number. The method is evaluated by simulation and is demonstrated on cell line data with known copy number alterations and on a breast cancer cell line data set.

Keywords: Array CGH; Binary segmentation; Change-point; ROMA


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E. A. Maher, C. Brennan, P. Y. Wen, L. Durso, K. L. Ligon, A. Richardson, D. Khatry, B. Feng, R. Sinha, D. N. Louis, et al.
Marked Genomic Differences Characterize Primary and Secondary Glioblastoma Subtypes and Identify Two Distinct Molecular and Clinical Secondary Glioblastoma Entities
Cancer Res., December 1, 2006; 66(23): 11502 - 11513.
[Abstract] [Full Text] [PDF]


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J. Bacteriol.Home page
H. Willenbrock, A. Petersen, C. Sekse, K. Kiil, Y. Wasteson, and D. W. Ussery
Design of a Seven-Genome Escherichia coli Microarray for Comparative Genomic Profiling
J. Bacteriol., November 15, 2006; 188(22): 7713 - 7721.
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Cancer Res.Home page
F. Liu, P. J. Park, W. Lai, E. Maher, A. Chakravarti, L. Durso, X. Jiang, Y. Yu, A. Brosius, M. Thomas, et al.
A Genome-Wide Screen Reveals Functional Gene Clusters in the Cancer Genome and Identifies EphA2 as a Mitogen in Glioblastoma
Cancer Res., November 15, 2006; 66(22): 10815 - 10823.
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Clin. Cancer Res.Home page
K. Trautmann, J. P. Terdiman, A. J. French, R. Roydasgupta, N. Sein, S. Kakar, J. Fridlyand, A. M. Snijders, D. G. Albertson, S. N. Thibodeau, et al.
Chromosomal Instability in Microsatellite-Unstable and Stable Colon Cancer.
Clin. Cancer Res., November 1, 2006; 12(21): 6379 - 6385.
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Cancer Res.Home page
T. Pejovic, J. E. Yates, H. Y. Liu, L. E. Hays, Y. Akkari, Y. Torimaru, W. Keeble, R. K. Rathbun, W. H. Rodgers, A. E. Bale, et al.
Cytogenetic instability in ovarian epithelial cells from women at risk of ovarian cancer.
Cancer Res., September 15, 2006; 66(18): 9017 - 9025.
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J. Mol. Diagn.Home page
G. Ng, J. Huang, I. Roberts, and N. Coleman
Defining Ploidy-Specific Thresholds in Array Comparative Genomic Hybridization to Improve the Sensitivity of Detection of Single Copy Alterations in Cell Lines
J. Mol. Diagn., September 1, 2006; 8(4): 449 - 458.
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BioinformaticsHome page
P. L. Rosa, E. Viara, P. Hupe, G. Pierron, S. Liva, P. Neuvial, I. Brito, S. Lair, N. Servant, N. Robine, et al.
VAMP: Visualization and analysis of array-CGH, transcriptome and other molecular profiles
Bioinformatics, September 1, 2006; 22(17): 2066 - 2073.
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BioinformaticsHome page
W. N. van Wieringen, J. A. M. Belien, S. J. Vosse, E. M. Achame, and B. Ylstra
ACE-it: a tool for genome-wide integration of gene dosage and RNA expression data
Bioinformatics, August 1, 2006; 22(15): 1919 - 1920.
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Proc. Natl. Acad. Sci. USAHome page
L. Zhang, J. Huang, N. Yang, J. Greshock, M. S. Megraw, A. Giannakakis, S. Liang, T. L. Naylor, A. Barchetti, M. R. Ward, et al.
microRNAs exhibit high frequency genomic alterations in human cancer
PNAS, June 13, 2006; 103(24): 9136 - 9141.
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Proc. Natl. Acad. Sci. USAHome page
J. C. Strefford, F. W. van Delft, H. M. Robinson, H. Worley, O. Yiannikouris, R. Selzer, T. Richmond, I. Hann, T. Bellotti, M. Raghavan, et al.
Complex genomic alterations and gene expression in acute lymphoblastic leukemia with intrachromosomal amplification of chromosome 21
PNAS, May 23, 2006; 103(21): 8167 - 8172.
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J. Mol. Diagn.Home page
G. Mohapatra, R. A. Betensky, E. R. Miller, B. Carey, L. D. Gaumont, D. A. Engler, and D. N. Louis
Glioma Test Array for Use with Formalin-Fixed, Paraffin-Embedded Tissue: Array Comparative Genomic Hybridization Correlates with Loss of Heterozygosity and Fluorescence in Situ Hybridization
J. Mol. Diagn., May 1, 2006; 8(2): 268 - 276.
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BioinformaticsHome page
J. C. Marioni, N. P. Thorne, and S. Tavare
BioHMM: a heterogeneous hidden Markov model for segmenting array CGH data
Bioinformatics, May 1, 2006; 22(9): 1144 - 1146.
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Cancer Res.Home page
J. Yao, S. Weremowicz, B. Feng, R. C. Gentleman, J. R. Marks, R. Gelman, C. Brennan, and K. Polyak
Combined cDNA array comparative genomic hybridization and serial analysis of gene expression analysis of breast tumor progression.
Cancer Res., April 15, 2006; 66(8): 4065 - 4078.
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BloodHome page
W. Chen, J. Houldsworth, A. B. Olshen, G. Nanjangud, S. Chaganti, E. S. Venkatraman, J. Halaas, J. Teruya-Feldstein, A. D. Zelenetz, and R. S. K. Chaganti
Array comparative genomic hybridization reveals genomic copy number changes associated with outcome in diffuse large B-cell lymphomas
Blood, March 15, 2006; 107(6): 2477 - 2485.
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BioinformaticsHome page
H. Willenbrock and J. Fridlyand
A comparison study: applying segmentation to array CGH data for downstream analyses
Bioinformatics, November 15, 2005; 21(22): 4084 - 4091.
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BioinformaticsHome page
T. Huang, B. Wu, P. Lizardi, and H. Zhao
Detection of DNA copy number alterations using penalized least squares regression
Bioinformatics, October 15, 2005; 21(20): 3811 - 3817.
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BioinformaticsHome page
W. R. Lai, M. D. Johnson, R. Kucherlapati, and P. J. Park
Comparative analysis of algorithms for identifying amplifications and deletions in array CGH data
Bioinformatics, October 1, 2005; 21(19): 3763 - 3770.
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BioinformaticsHome page
M. A. van de Wiel, S. J. Smeets, R. H. Brakenhoff, and B. Ylstra
CGHMultiArray: exact P-values for multi-array comparative genomic hybridization data
Bioinformatics, July 15, 2005; 21(14): 3193 - 3194.
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Cancer Res.Home page
X. Zhao, B. A. Weir, T. LaFramboise, M. Lin, R. Beroukhim, L. Garraway, J. Beheshti, J. C. Lee, K. Naoki, W. G. Richards, et al.
Homozygous Deletions and Chromosome Amplifications in Human Lung Carcinomas Revealed by Single Nucleotide Polymorphism Array Analysis
Cancer Res., July 1, 2005; 65(13): 5561 - 5570.
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