Advertisement

A Linear-Time Algorithm for Analyzing Array CGH Data Using Log Ratio Triangulation

  • Matthew Hayes
  • Jing Li
Part of the Lecture Notes in Computer Science book series (LNCS, volume 5542)

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.

Keywords

False Discovery Rate Array Comparative Genomic Hybridization Copy Number Alteration Copy Number Aberration Noise Standard Deviation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    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)PubMedGoogle Scholar
  2. 2.
    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)CrossRefPubMedGoogle Scholar
  3. 3.
    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)CrossRefPubMedGoogle Scholar
  4. 4.
    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)CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Wang, Y., Makedon, F., Pearlman, J.: Tumor classification based on DNA copy number aberrations determined using SNP arrays. Oncology Reports 15, 1057–1061 (2006)PubMedGoogle Scholar
  6. 6.
    Pinkel, D., Albertson, D.G.: Array comparative genomic hybridization and its applications in cancer. Nat. Genet. 37, suppl. S11–S17 (2005)CrossRefGoogle Scholar
  7. 7.
    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)CrossRefGoogle Scholar
  8. 8.
    Olshen, A., Venkatraman, E.: Circular binary segmentation for the analysis of array-based DNA copy number data. Biostatistics 5, 557–572 (2004)CrossRefPubMedGoogle Scholar
  9. 9.
    Willenbrock, H., Fridlyand, J.: A comparison study: applying segmentation to array CGH data for downstream analyses. Bioinformatics 21(22), 4084–4091 (2005)CrossRefPubMedGoogle Scholar
  10. 10.
    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)CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Venkatraman, E., Olshen, A.: A Faster Circular Binary Segmentation Algorithm for the Analysis of Array CGH Data. Bioinformatics 23(6), 657–663 (2007)CrossRefPubMedGoogle Scholar
  12. 12.
    Guha, S., Li, Y., Neuberg, D.: Bayesian Hidden Markov Modeling of Array CGH Data. Harvard University Biostatistics Working Paper Series. Working Paper 24 (2006)Google Scholar
  13. 13.
    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, 132Google Scholar
  14. 14.
    Durbin, R., et al.: Biological Sequence Analysis. Cambridge University Press, Cambridge (1999)Google Scholar
  15. 15.
    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)CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    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)CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Carter, N.P.: Methods and strategies for analyzing copy number variation using dna microarrays. Nat. Genet. 39(suppl. 7), S16–S21 (2007)CrossRefGoogle Scholar
  18. 18.
    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)CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Matthew Hayes
    • 1
  • Jing Li
    • 1
  1. 1.Case Western Reserve UniversityClevelandUSA

Personalised recommendations