title: Comprehensive assessment of array-based platforms and calling algorithms for detection of copy number variants.
abstract: We have systematically compared copy number variant (CNV) detection on eleven microarrays to evaluate data quality and CNV calling, reproducibility, concordance across array platforms and laboratory sites, breakpoint accuracy and analysis tool variability. Different analytic tools applied to the same raw data typically yield CNV calls with <50% concordance. Moreover, reproducibility in replicate experiments is <70% for most platforms. Nevertheless, these findings should not preclude detection of large CNVs for clinical diagnostic purposes because large CNVs with poor reproducibility are found primarily in complex genomic regions and would typically be removed by standard clinical data curation. The striking differences between CNV calls from different platforms and analytic tools highlight the importance of careful assessment of experimental design in discovery and association studies and of strict data curation and filtering in diagnostics. The CNV resource presented here allows independent data evaluation and provides a means to benchmark new algorithms.
authors.affiliation: The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Dalila
authors.initials: D
authors.lastname: Pinto
authors.forename: Katayoon
authors.initials: K
authors.lastname: Darvishi
authors.forename: Xinghua
authors.initials: X
authors.lastname: Shi
authors.forename: Diana
authors.initials: D
authors.lastname: Rajan
authors.forename: Diane
authors.initials: D
authors.lastname: Rigler
authors.forename: Tom
authors.initials: T
authors.lastname: Fitzgerald
authors.forename: Anath C
authors.initials: AC
authors.lastname: Lionel
authors.forename: Bhooma
authors.initials: B
authors.lastname: Thiruvahindrapuram
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Macdonald
authors.forename: Ryan
authors.initials: R
authors.lastname: Mills
authors.forename: Aparna
authors.initials: A
authors.lastname: Prasad
authors.forename: Kristin
authors.initials: K
authors.lastname: Noonan
authors.forename: Susan
authors.initials: S
authors.lastname: Gribble
authors.forename: Elena
authors.initials: E
authors.lastname: Prigmore
authors.forename: Patricia K
authors.initials: PK
authors.lastname: Donahoe
authors.forename: Richard S
authors.initials: RS
authors.lastname: Smith
authors.forename: Ji Hyeon
authors.initials: JH
authors.lastname: Park
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Hurles
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Carter
authors.forename: Charles
authors.initials: C
authors.lastname: Lee
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.forename: Lars
authors.initials: L
authors.lastname: Feuk
mesh_terms: D000465:Algorithms; D055028:Comparative Genomic Hybridization / Q000379:methods*; D056915:DNA Copy Number Variations; D030541:Databases, Genetic; D056726:Genetic Association Studies; D016678:Genome; D005838:Genotype; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D012984:Software