Analysis of array CGH data: from signal ratio to gain and loss of DNA regions (original) (raw)

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Revision received:

18 June 2004

Published:

30 September 2004

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Philippe Hupé, Nicolas Stransky, Jean-Paul Thiery, François Radvanyi, Emmanuel Barillot, Analysis of array CGH data: from signal ratio to gain and loss of DNA regions, Bioinformatics, Volume 20, Issue 18, December 2004, Pages 3413–3422, https://doi.org/10.1093/bioinformatics/bth418
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Abstract

Motivation: Genomic DNA regions are frequently lost or gained during tumor progression. Array Comparative Genomic Hybridization (array CGH) technology makes it possible to assess these changes in DNA in cancers, by comparison with a normal reference. The identification of systematically deleted or amplified genomic regions in a set of tumors enables biologists to identify genes involved in cancer progression because tumor suppressor genes are thought to be located in lost genomic regions and oncogenes, in gained regions. Array CGH profiles should also improve the classification of tumors. The achievement of these goals requires a methodology for detecting the breakpoints delimiting altered regions in genomic patterns and assigning a status (normal, gained or lost) to each chromosomal region.

Results: We have developed a methodology for the automatic detection of breakpoints from array CGH profile, and the assignment of a status to each chromosomal region. The breakpoint detection step is based on the Adaptive Weights Smoothing (AWS) procedure and provides highly convincing results: our algorithm detects 97, 100 and 94% of breakpoints in simulated data, karyotyping results and manually analyzed profiles, respectively. The percentage of correctly assigned statuses ranges from 98.9 to 99.8% for simulated data and is 100% for karyotyping results. Our algorithm also outperforms other solutions on a public reference dataset.

Availability: The R package GLAD (Gain and Loss Analysis of DNA) is available upon request

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1Service Bioinformatique and 2UMR 144 CNRS/Institut Curie, 26, rue d'Ulm, Paris, 75248 cedex 05, France

Bioinformatics vol. 20 issue 18 © Oxford University Press 2004; all rights reserved.

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