Abstract
DNA copy number is the number of replicates of a contiguous segment of DNA on the genome. Copy number alteration (CNA) is a genetic abnormality in which the number of these segments differs from the normal copy number, which is two for human chromosomal DNA. The association of CNA with cancer has led to a proliferation of research into algorithmic methods for detecting these regions of genetic abnormality. We propose a linear-time algorithm to identify chromosomal change points using array comparative genomic hybridization (aCGH) data. This method treats log-2 ratio values as points in a triangle and segments the genome into regions of equal copy number by exploiting the properties of log-2 ratio values often seen at segment boundaries. Applying our method to real and simulated aCGH datasets shows that the triangulation method is fast and is robust for data with low to moderate noise levels.
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References
Veltman, J.A., Fridlyand, J., Pejavar, S., Olshen, A., Korkola, J., DeVries, S., Carroll, P., Kuo, W., Pinkel, D., Albertson, D., Cordon-Cardo, C., Jain, A., Waldman, F.: Array-based comparative genomic hybridization for genome-wide screening of DNA copy number in bladder tumors. Cancer Res. 63, 2872–2880 (2003)
Whang-Peng, J., Kao-Shan, C., Lee, E., Bunn, P., Carney, D., Gadzar, A., Minna, J.: Specific chromosome defect associated with human small cell lung cancer; deletion 3p(14-23). Science 215, 181–182 (1982)
de Leeuw, R., Davies, J., Rosenwald, A., Bebb, G., Gascoyne, D., Dyer, M., Staudt, L., Martinez-Climent, J., Lam, W.: Comprehensive whole genome array cgh profiling of mantle cell lymphoma model genomes. Hum. Mol. Genet. 13(17), 1827–1837 (2004)
Fridlyand, J., Snijders, A., Ylstra, B., Li, H., Olshen, A., Segraves, R., Dairkee, Shanaz, Tokuasu, T., Ljung, B., Jain, A., McLenna, J., Ziegler, J., Chin, K., DeVries, S., Feiler, H., Gray, J., Waldman, F., Pinkel, D., Albertson, D.: Breast tumor copy number aberration phenotypes and genomic instability. BMC Cancer 6, 96 (2006)
Wang, Y., Makedon, F., Pearlman, J.: Tumor classification based on DNA copy number aberrations determined using SNP arrays. Oncology Reports 15, 1057–1061 (2006)
Pinkel, D., Albertson, D.G.: Array comparative genomic hybridization and its applications in cancer. Nat. Genet. 37, suppl. S11–S17 (2005)
Snijders, A., Nowak, N., Segraves, R., Blackwood, S., Brown, N., Conroy, J., Hamilton, G., Hindle, A., Huey, B., Kimura, K., Law, S., Myambo, K., Palmer, J., Ylstra, B., Yue, J., Gray, J., Jain, A., Pinkel, D., Albertson, D.: Assembly of microarrays for genome-wide measurement of DNA copy number. Nat. Genet. 3, 263–264 (2001)
Olshen, A., Venkatraman, E.: Circular binary segmentation for the analysis of array-based DNA copy number data. Biostatistics 5, 557–572 (2004)
Willenbrock, H., Fridlyand, J.: A comparison study: applying segmentation to array CGH data for downstream analyses. Bioinformatics 21(22), 4084–4091 (2005)
Lai, W., Johnson, M., Kucherlapati, R., Park, P.: Comparative analysis of algorithms for identifying amplifications and deletions in array CGH data. Bioinformatics 21, 3763–3770 (2005)
Venkatraman, E., Olshen, A.: A Faster Circular Binary Segmentation Algorithm for the Analysis of Array CGH Data. Bioinformatics 23(6), 657–663 (2007)
Guha, S., Li, Y., Neuberg, D.: Bayesian Hidden Markov Modeling of Array CGH Data. Harvard University Biostatistics Working Paper Series. Working Paper 24 (2006)
Fridlyand, J., Snijders, A., Pinkel, D., Albertson, D., Jain, A.: Hidden Markov models approach to the analysis of array CGH data. J. Multivar. Anal. 90, 132
Durbin, R., et al.: Biological Sequence Analysis. Cambridge University Press, Cambridge (1999)
Daruwala, R., Rudra, A., Ostrer, H., Lucito, R., Wigler, M., Mishra, B.: A versatile statistical analysis algorithm to detect genome copy number variation. Proc. Natl. Acad. Sci. 101(46), 16292–16297 (2004)
Redon, R., Ishikawa, S., Fitch, K.R., Feuk, L., Perry, G.H., Andrews, T.D., Fiegler, H., Shapero, M.H., Carson, A.R., Chen, W., Cho, E.K., Dallaire, S., Freeman, J.L., Gonzalez, J.R., Gratacos, M., Huang, J., Kalaitzopoulos, D., Komura, D., MacDonald, J.R., Marshall, C.R., Mei, R., Montgomery, L., Nishimura, K., Okamura, K., Shen, F., Somerville, M.J., Tchinda, J., Valsesia, A., Woodwark, C., Yang, F., Zhang, J., Zerjal, T., Armengol, L., Conrad, D.F., Estivill, X., Tyler-Smith, C., Carter, N.P., Aburatani, H., Lee, C., Jones, K.W., Scherer, S.W., Hurles, M.E.: Global variation in copy number in the human genome. Nature 444(7118), 444–454 (2006)
Carter, N.P.: Methods and strategies for analyzing copy number variation using dna microarrays. Nat. Genet. 39(suppl. 7), S16–S21 (2007)
Chiang, D.Y., Getz, G., Jaffe, D.B., O’Kelly, M.J., Zhao, X., Carter, S.L., Russ, C., Nusbaum, C., Meyerson, M., Lander, E.S.: High-resolution mapping of copy-number alterations with massively parallel sequencing. Nat. Methods 6(1), 99–103 (2009)
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Hayes, M., Li, J. (2009). A Linear-Time Algorithm for Analyzing Array CGH Data Using Log Ratio Triangulation. In: Măndoiu, I., Narasimhan, G., Zhang, Y. (eds) Bioinformatics Research and Applications. ISBRA 2009. Lecture Notes in Computer Science(), vol 5542. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-01551-9_25
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DOI: https://doi.org/10.1007/978-3-642-01551-9_25
Publisher Name: Springer, Berlin, Heidelberg
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