title: aCGH.Spline--an R package for aCGH dye bias normalization.
abstract: BACKGROUND
  The careful normalization of array-based comparative genomic hybridization (aCGH) data is of critical importance for the accurate detection of copy number changes. The difference in labelling affinity between the two fluorophores used in aCGH-usually Cy5 and Cy3-can be observed as a bias within the intensity distributions. If left unchecked, this bias is likely to skew data interpretation during downstream analysis and lead to an increased number of false discoveries.
  
  
  RESULTS
  In this study, we have developed aCGH.Spline, a natural cubic spline interpolation method followed by linear interpolation of outlier values, which is able to remove a large portion of the dye bias from large aCGH datasets in a quick and efficient manner.
  
  
  CONCLUSIONS
  We have shown that removing this bias and reducing the experimental noise has a strong positive impact on the ability to detect accurately both copy number variation (CNV) and copy number alterations (CNA).
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK. tf2@sanger.ac.uk
authors.forename: Tomas W
authors.initials: TW
authors.lastname: Fitzgerald
authors.forename: Lee D
authors.initials: LD
authors.lastname: Larcombe
authors.forename: Solena
authors.initials: S
authors.lastname: Le Scouarnec
authors.forename: Stephen
authors.initials: S
authors.lastname: Clayton
authors.forename: Diana
authors.initials: D
authors.lastname: Rajan
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Carter
authors.forename: Richard
authors.initials: R
authors.lastname: Redon
mesh_terms: D002232:Carbocyanines / Q000737:chemistry; D055028:Comparative Genomic Hybridization / Q000379:methods*; D056915:DNA Copy Number Variations; D005456:Fluorescent Dyes / Q000737:chemistry*; D012984:Software
chemical_list: D002232:Carbocyanines; D005456:Fluorescent Dyes; C089187:cyanine dye 3; C085321:cyanine dye 5