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Nucleic Acids Research 2005 33(11):3455-3464; doi:10.1093/nar/gki643
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Published online 16 June 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
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Article

SW-ARRAY: a dynamic programming solution for the identification of copy-number changes in genomic DNA using array comparative genome hybridization data

Thomas S. Price1, Regina Regan2, Richard Mott1, Åsa Hedman1, Ben Honey2, Rachael J. Daniels4, Lee Smith3, Andy Greenfield3, Ana Tiganescu1, Veronica Buckle4, Nicki Ventress4, Helena Ayyub4, Anita Salhan1, Susana Pedraza-Diaz1, John Broxholme1, Jiannis Ragoussis1, Douglas R. Higgs4, Jonathan Flint1 and Samantha J. L. Knight1,2,*

1The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Churchill Hospital Headington, Oxford OX3 7BN, UK 2Oxford Genetics Knowledge Park, Roosevelt Drive, Churchill Hospital Headington, Oxford OX3 7BN, UK 3Mammalian Genetics Unit, Medical Research Council Harwell, Didcot, OX11 0RD, UK 4Weatherall Institute of Molecular Medicine, John Radcliffe Hospital Headley Way, Headington, Oxford OX3 9DS, UK

*To whom correspondence should be addressed at The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Churchill Hospital, Headington, Oxford OX3 7BN, UK. Tel: +44 1865 287511; Fax: +44 1865 287501; Email: sknight{at}well.ox.ac.uk

Received April 21, 2005. Accepted May 20, 2005.

Comparative genome hybridization (CGH) to DNA microarrays (array CGH) is a technique capable of detecting deletions and duplications in genomes at high resolution. However, array CGH studies of the human genome noting false negative and false positive results using large insert clones as probes have raised important concerns regarding the suitability of this approach for clinical diagnostic applications. Here, we adapt the Smith–Waterman dynamic-programming algorithm to provide a sensitive and robust analytic approach (SW-ARRAY) for detecting copy-number changes in array CGH data. In a blind series of hybridizations to arrays consisting of the entire tiling path for the terminal 2 Mb of human chromosome 16p, the method identified all monosomies between 267 and 1567 kb with a high degree of statistical significance and accurately located the boundaries of deletions in the range 267–1052 kb. The approach is unique in offering both a nonparametric segmentation procedure and a nonparametric test of significance. It is scalable and well-suited to high resolution whole genome array CGH studies that use array probes derived from large insert clones as well as PCR products and oligonucleotides.

The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors


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