title: CGHnormaliter: an iterative strategy to enhance normalization of array CGH data with imbalanced aberrations.
abstract: BACKGROUND
  Array comparative genomic hybridization (aCGH) is a popular technique for detection of genomic copy number imbalances. These play a critical role in the onset of various types of cancer. In the analysis of aCGH data, normalization is deemed a critical pre-processing step. In general, aCGH normalization approaches are similar to those used for gene expression data, albeit both data-types differ inherently. A particular problem with aCGH data is that imbalanced copy numbers lead to improper normalization using conventional methods.
  
  
  RESULTS
  In this study we present a novel method, called CGHnormaliter, which addresses this issue by means of an iterative normalization procedure. First, provisory balanced copy numbers are identified and subsequently used for normalization. These two steps are then iterated to refine the normalization. We tested our method on three well-studied tumor-related aCGH datasets with experimentally confirmed copy numbers. Results were compared to a conventional normalization approach and two more recent state-of-the-art aCGH normalization strategies. Our findings show that, compared to these three methods, CGHnormaliter yields a higher specificity and precision in terms of identifying the 'true' copy numbers.
  
  
  CONCLUSIONS
  We demonstrate that the normalization of aCGH data can be significantly enhanced using an iterative procedure that effectively eliminates the effect of imbalanced copy numbers. This also leads to a more reliable assessment of aberrations. An R-package containing the implementation of CGHnormaliter is available at http://www.ibi.vu.nl/programs/cghnormaliterwww.
authors.affiliation: Centre for Integrative Bioinformatics VU (IBIVU), VU University Amsterdam, De Boelelaan 1081A, 1081 HV Amsterdam, the Netherlands.
authors.forename: Bart P P
authors.initials: BP
authors.lastname: van Houte
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Binsl
authors.forename: Hannes
authors.initials: H
authors.lastname: Hettling
authors.forename: Walter
authors.initials: W
authors.lastname: Pirovano
authors.forename: Jaap
authors.initials: J
authors.lastname: Heringa
mesh_terms: D055028:Comparative Genomic Hybridization / Q000379:methods*; D004273:DNA, Neoplasm / Q000235:genetics; D018628:Gene Dosage; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods
chemical_list: D004273:DNA, Neoplasm