title: Finding recurrent copy number alterations preserving within-sample homogeneity.
abstract: BACKGROUND
  Copy number alterations (CNAs) represent an important component of genetic variation and play a significant role in many human diseases. Development of array comparative genomic hybridization (aCGH) technology has made it possible to identify CNAs. Identification of recurrent CNAs represents the first fundamental step to provide a list of genomic regions which form the basis for further biological investigations. The main problem in recurrent CNAs discovery is related to the need to distinguish between functional changes and random events without pathological relevance. Within-sample homogeneity represents a common feature of copy number profile in cancer, so it can be used as additional source of information to increase the accuracy of the results. Although several algorithms aimed at the identification of recurrent CNAs have been proposed, no attempt of a comprehensive comparison of different approaches has yet been published.
  
  
  RESULTS
  We propose a new approach, called Genomic Analysis of Important Alterations (GAIA), to find recurrent CNAs where a statistical hypothesis framework is extended to take into account within-sample homogeneity. Statistical significance and within-sample homogeneity are combined into an iterative procedure to extract the regions that likely are involved in functional changes. Results show that GAIA represents a valid alternative to other proposed approaches. In addition, we perform an accurate comparison by using two real aCGH datasets and a carefully planned simulation study.
  
  
  BACKGROUND
  GAIA has been implemented as R/Bioconductor package. It can be downloaded from the following page http://bioinformatics.biogem.it/download/gaia.
  
  
  BACKGROUND
  ceccarelli@unisannio.it; morganella@unisannio.it.
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Science, University of Sannio, 82100, Benevento, Italy. morganella@unisannio.it
authors.forename: Sandro
authors.initials: S
authors.lastname: Morganella
authors.forename: Stefano Maria
authors.initials: SM
authors.lastname: Pagnotta
authors.forename: Michele
authors.initials: M
authors.lastname: Ceccarelli
mesh_terms: D000465:Algorithms; D055028:Comparative Genomic Hybridization; D056914:Genomic Structural Variation; D023281:Genomics; D006801:Humans; D009369:Neoplasms / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods