title: SW-ARRAY: a dynamic programming solution for the identification of copy-number changes in genomic DNA using array comparative genome hybridization data.
abstract: 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.
authors.affiliation: The Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Churchill Hospital Headington, Oxford OX3 7BN, UK.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Price
authors.forename: Regina
authors.initials: R
authors.lastname: Regan
authors.forename: Richard
authors.initials: R
authors.lastname: Mott
authors.forename: Asa
authors.initials: A
authors.lastname: Hedman
authors.forename: Ben
authors.initials: B
authors.lastname: Honey
authors.forename: Rachael J
authors.initials: RJ
authors.lastname: Daniels
authors.forename: Lee
authors.initials: L
authors.lastname: Smith
authors.forename: Andy
authors.initials: A
authors.lastname: Greenfield
authors.forename: Ana
authors.initials: A
authors.lastname: Tiganescu
authors.forename: Veronica
authors.initials: V
authors.lastname: Buckle
authors.forename: Nicki
authors.initials: N
authors.lastname: Ventress
authors.forename: Helena
authors.initials: H
authors.lastname: Ayyub
authors.forename: Anita
authors.initials: A
authors.lastname: Salhan
authors.forename: Susana
authors.initials: S
authors.lastname: Pedraza-Diaz
authors.forename: John
authors.initials: J
authors.lastname: Broxholme
authors.forename: Jiannis
authors.initials: J
authors.lastname: Ragoussis
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Higgs
authors.forename: Jonathan
authors.initials: J
authors.lastname: Flint
authors.forename: Samantha J L
authors.initials: SJ
authors.lastname: Knight
mesh_terms: D000465:Algorithms; D000782:Aneuploidy; D002872:Chromosome Deletion; D019295:Computational Biology / Q000379:methods*; D015342:DNA Probes; D015894:Genome, Human; D023281:Genomics / Q000379:methods*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012984:Software
chemical_list: D015342:DNA Probes