Framework for identifying common aberrations in DNA copy number data

Amir Ben-Dor, Doron Lipson, Anya Tsalenko, Mark Reimers, Lars O. Baumbusch, Michael Barrett, John N. Weinstein, Anne Lise Børresen-Dale, Zohar Yakhini

Research output: Chapter in Book/Report/Conference proceedingConference contribution

13 Citations (Scopus)

Abstract

High-resolution array comparative genomic hybridization (aCGH) provides exon-level mapping of DNA aberrations in cells or tissues. Such aberrations are central to carcinogenesis and, in many cases, central to targeted therapy of the cancers. Some of the aberrations are sporadic, one-of-a-kind changes in particular tumor samples; others occur frequently and reflect common themes in cancer biology that have interpretable, causal ramifications. Hence, the difficult task of identifying and mapping common, overlapping genomic aberrations (including amplifications and deletions) across a sample set is an important one; it can provide insight for the discovery of oncogenes, tumor suppressors, and the mechanisms by which they drive cancer development. In this paper we present an efficient computational framework for identification and statistical characterization of genomic aberrations that are common to multiple cancer samples in a CGH data set. We present and compare three different algorithmic approaches within the context of that framework. Finally, we apply our methods to two datasets - a collection of 20 breast cancer samples and a panel of 60 diverse human tumor cell lines (the NCI-60). Those analyses identified both known and novel common aberrations containing cancer-related genes. The potential impact of the analytical methods is well demonstrated by new insights into the patterns of deletion of CDKN2A (p16), a tumor suppressor gene crucial for the genesis of many types of cancer.

Original languageEnglish (US)
Title of host publicationLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Pages122-136
Number of pages15
Volume4453 LNBI
StatePublished - 2007
Externally publishedYes
Event11th Annual International Conference on Research in Computational Molecular Biology, RECOMB 2007 - Oakland, CA, United States
Duration: Apr 21 2007Apr 25 2007

Other

Other11th Annual International Conference on Research in Computational Molecular Biology, RECOMB 2007
CountryUnited States
CityOakland, CA
Period4/21/074/25/07

Fingerprint

Aberrations
Aberration
Cancer
DNA
Tumors
Tumor
Neoplasms
Deletion
Genomics
Genes
Gene
Comparative Genomics
Carcinogenesis
Cell
Ramification
Comparative Genomic Hybridization
Breast Cancer
Analytical Methods
Neoplasm Genes
Amplification

Keywords

  • Breast cancer
  • Cancer
  • CGH
  • Common aberrations
  • Microarray data analysis
  • NCI-60

ASJC Scopus subject areas

  • Computer Science(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Theoretical Computer Science

Cite this

Ben-Dor, A., Lipson, D., Tsalenko, A., Reimers, M., Baumbusch, L. O., Barrett, M., ... Yakhini, Z. (2007). Framework for identifying common aberrations in DNA copy number data. In Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) (Vol. 4453 LNBI, pp. 122-136)

Framework for identifying common aberrations in DNA copy number data. / Ben-Dor, Amir; Lipson, Doron; Tsalenko, Anya; Reimers, Mark; Baumbusch, Lars O.; Barrett, Michael; Weinstein, John N.; Børresen-Dale, Anne Lise; Yakhini, Zohar.

Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). Vol. 4453 LNBI 2007. p. 122-136.

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Ben-Dor, A, Lipson, D, Tsalenko, A, Reimers, M, Baumbusch, LO, Barrett, M, Weinstein, JN, Børresen-Dale, AL & Yakhini, Z 2007, Framework for identifying common aberrations in DNA copy number data. in Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). vol. 4453 LNBI, pp. 122-136, 11th Annual International Conference on Research in Computational Molecular Biology, RECOMB 2007, Oakland, CA, United States, 4/21/07.
Ben-Dor A, Lipson D, Tsalenko A, Reimers M, Baumbusch LO, Barrett M et al. Framework for identifying common aberrations in DNA copy number data. In Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). Vol. 4453 LNBI. 2007. p. 122-136
Ben-Dor, Amir ; Lipson, Doron ; Tsalenko, Anya ; Reimers, Mark ; Baumbusch, Lars O. ; Barrett, Michael ; Weinstein, John N. ; Børresen-Dale, Anne Lise ; Yakhini, Zohar. / Framework for identifying common aberrations in DNA copy number data. Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics). Vol. 4453 LNBI 2007. pp. 122-136
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