title: PICNIC: an algorithm to predict absolute allelic copy number variation with microarray cancer data.
abstract: High-throughput oligonucleotide microarrays are commonly employed to investigate genetic disease, including cancer. The algorithms employed to extract genotypes and copy number variation function optimally for diploid genomes usually associated with inherited disease. However, cancer genomes are aneuploid in nature leading to systematic errors when using these techniques. We introduce a preprocessing transformation and hidden Markov model algorithm bespoke to cancer. This produces genotype classification, specification of regions of loss of heterozygosity, and absolute allelic copy number segmentation. Accurate prediction is demonstrated with a combination of independent experimental techniques. These methods are exemplified with affymetrix genome-wide SNP6.0 data from 755 cancer cell lines, enabling inference upon a number of features of biological interest. These data and the coded algorithm are freely available for download.
authors.affiliation: Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. cdg@sanger.ac.uk
authors.forename: Chris D
authors.initials: CD
authors.lastname: Greenman
authors.forename: Graham
authors.initials: G
authors.lastname: Bignell
authors.forename: Adam
authors.initials: A
authors.lastname: Butler
authors.forename: Sarah
authors.initials: S
authors.lastname: Edkins
authors.forename: Jon
authors.initials: J
authors.lastname: Hinton
authors.forename: Dave
authors.initials: D
authors.lastname: Beare
authors.forename: Sajani
authors.initials: S
authors.lastname: Swamy
authors.forename: Thomas
authors.initials: T
authors.lastname: Santarius
authors.forename: Lina
authors.initials: L
authors.lastname: Chen
authors.forename: Sara
authors.initials: S
authors.lastname: Widaa
authors.forename: P Andy
authors.initials: PA
authors.lastname: Futreal
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stratton
mesh_terms: D000465:Algorithms; D000483:Alleles; D000782:Aneuploidy; D001499:Bayes Theorem; D015982:Bias; D045744:Cell Line, Tumor; D056915:DNA Copy Number Variations / Q000235:genetics*; D016147:Genes, Tumor Suppressor; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D020407:Internet; D019656:Loss of Heterozygosity / Q000235:genetics; D008390:Markov Chains; D015233:Models, Statistical; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011123:Polyploidy; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012984:Software