Chromosomal Breakpoint Detection in Human Cancer
Chromosomal aberrations are differences in DNA sequence copy number of chromosome regions1. These differences may be crucial genetic events in the development and progression of human cancers. Array Comparative Genomic Hybridization is a laboratory method used in cancer research for the measurement of chromosomal aberrations in tumor genomes. A recurrent aberration at a particular genome location may indicate the presence of a tumor suppressor gene or an oncogene. The goal of the analysis of this type of data includes detection of locations of copy number changes, called breakpoints, and estimate of the values of the copy number value before and after a change. Knowing the exact locations of a breakpoint is important to identify possibly damaged genes. This paper introduces genetic local search algorithms to perform this task.
KeywordsLocal Search Memetic Algorithm Copy Number Change Array Comparative Genomic Hybridization Normal Probability Plot
Unable to display preview. Download preview PDF.
- 1.H. Akaike. Information theory and an extension of the maximum likelihood principle. In B. Petrox and F. Caski, editors, Second International Symposium on Information Theory, page 267, 1973.Google Scholar
- 2.J. Fridlyand. Personal communication, 2002.Google Scholar
- 4.P. Moscato. On evolution, search, optimization, genetic algorithms and martial arts: Towards memetic algorithms. Technical report, Caltech Concurrent Computation Program, Californian Institute of Technology, U.S.A., TR No790 1989.Google Scholar
- 5.D. Pinkel, R. Segraves, D. Sudar, S. Clark, I. Poole, D. Kowbel, C. Collins, W.L. Kuo, C. Chen, Y. Zhai, S.H. Dairkee, B.M. Ljung, J.W. Gray, and D.G. Albertson. High resolution analysis of dna copy number variation using comparative genomic hybridization to microarrays. Nature Genetics, 20, 1998.Google Scholar
- 6.J.A. Rice. Mathematical Statistics and Data Analysis Second Edition. Duxbury Press, 1995.Google Scholar
- 8.A.M. Snijders, N. Nowak, R. Segraves, S. Blackwood, N. Brown, J. Conroy, G. Hamilton, A.K. Hindle, B. Huey, K. Kimura, S. Law, K. Myambo, J. Palmer, B. Ylstra, J.P. Yue, J.W. Gray, A.N. Jain, D. Pinkel, and D.G. Albertson. Assembly of microarrays for genome-wide measurement of dna copy number by cgh. Nature Genetics, 29:263–264, 2001.CrossRefGoogle Scholar
- 9.M.M. Weiss, E.J. Kuipers, C. Postma, A. M. Snijders, I. Siccama, D. Pinkel, J. Westerga, S.G.M. Meuwissen, D. G. Albertson, and G.A. Meijer. Genomic profiling of gastric cancer predicts lymph node status survival. Oncogene, 2003. In press.Google Scholar