Abstract
Genomic instabilities, amplifications, deletions and translocations are often observed in tumor cells. In the process of cancer pathogenesis cells acquire multiple genomic alterations, some of which drive the process by triggering overexpression of oncogenes and by silencing tumor suppressors and DNA repair genes. We present data analysis methods designed to study the overall transcriptional effects of DNA copy number alterations. Alterations can be measured using several techniques including microarray based hybridization assays. The data have unique properties due to the strong dependence between measurement values in close genomic loci. To account for this dependence in studying the correlation of DNA copy number to expression levels we develop versions of standard correlation methods that apply to genomic regions and methods for assessing the statistical significance of the observed results. In joint DNA copy number and expression data we define significantly altered submatrices as submatrices where a statistically significant correlation of DNA copy number to expression is observed. We develop heuristic approaches to identify these structures in data matrices. We apply all methods to several datasets, highlighting results that can not be obtained by direct approaches or without using the regional view.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Supplement data, available at http://bioinfo.cs.technion.ac.il/cghexp/
Balsara, B.R., Testa, J.R.: Chromosomal imbalances in human lung cancer. Oncogene 21(45), 6877–6883 (2002)
Ben-Dor, A., Bruhn, L., Friedman, N., Nachman, I., Schummer, M., Yakhini, Z.: Tissue classification with gene expression profiles. In: Proceedings of RECOMB, pp. 54–64 (2000)
Ben-Dor, A., Friedman, N., Yakhini, Z.: Class discovery in gene expression data. In: Proceedings of RECOMB, pp. 31–38 (2001)
Bittner, M., et al.: Molecular classification of cutaneous malignant melanoma by gene expression profiling. Nature 406(6795), 536–540 (2000)
Hedenfalk, I., et al.: Molecular classification of familial non-BRCA1/BRCA2 breast cancer. PNAS 100(5), 2532–2537 (2003)
Hyman, E., Kauraniemi, P., Hautaniemi, S., Wolf, M., Mousses, S., Rozenblum, E., Ringner, M., Sauter, G., Monni, O., Elkahloun, A., Kallioniemi, O.P., Kallioniemi, A.: Impact of DNA amplification on gene expression patterns in breast cancer. Cancer Research 62, 6240–6245 (2002)
Kallioniemi, O.P., Kallioniemi, A., Sudar, D., Rutovitz, D., Gray, J., Waldman, F., Pinkel, D.: Comparative genomic hybridization: a rapid new method for detecting and mapping DNA amplification in tumors. Semin Cancer Biol. 4(1), 41–46 (1993)
Linn, S.C., et al.: Gene expression patterns and gene copy number changes in DFSP. Amer J of Pathology 163(6), 2383–2395 (2003)
Mertens, F., Johansson, B., Hoglund, M., Mitelman, F.: Chromosomal imbalance maps of malignant solid tumors: a cytogenetic survey of 3185 neoplasms. Cancer Research 57(13), 2765–2780 (1997)
Pinkel, D., et al.: High resolution analysis of DNA copy number variation using comparative genomic hybridization to microarrays. Nat. Gen. 20(2), 207–211 (1998)
Platzer, P., et al.: Silence of chromosomal amplifications in colon cancer. Cancer Research 62(4), 1134–1138 (2002)
Pollack, J.R., Perou, C.M., Alizadeh, A.A., Eisen, M.B., Pergamenschikov, A., Williams, C.F., Jeffrey, S.S., Botstein, D., Brown, P.O.: Genome-wide analysis of DNA copy-number changes using cDNA microarrays. Nature Genetics 23(1), 41–46 (1999)
Pollack, J.R., et al.: Microarray analysis reveals a major direct role of DNA copy number alteration in the transcriptional program of human breast tumors. PNAS 99(20), 12963–12968 (2002)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2004 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Lipson, D., Ben-Dor, A., Dehan, E., Yakhini, Z. (2004). Joint Analysis of DNA Copy Numbers and Gene Expression Levels. In: Jonassen, I., Kim, J. (eds) Algorithms in Bioinformatics. WABI 2004. Lecture Notes in Computer Science(), vol 3240. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-30219-3_12
Download citation
DOI: https://doi.org/10.1007/978-3-540-30219-3_12
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-23018-2
Online ISBN: 978-3-540-30219-3
eBook Packages: Springer Book Archive