title: WaveCNV: allele-specific copy number alterations in primary tumors and xenograft models from next-generation sequencing.
abstract: BACKGROUND
  Copy number variations (CNVs) are a major source of genomic variability and are especially significant in cancer. Until recently microarray technologies have been used to characterize CNVs in genomes. However, advances in next-generation sequencing technology offer significant opportunities to deduce copy number directly from genome sequencing data. Unfortunately cancer genomes differ from normal genomes in several aspects that make them far less amenable to copy number detection. For example, cancer genomes are often aneuploid and an admixture of diploid/non-tumor cell fractions. Also patient-derived xenograft models can be laden with mouse contamination that strongly affects accurate assignment of copy number. Hence, there is a need to develop analytical tools that can take into account cancer-specific parameters for detecting CNVs directly from genome sequencing data.
  
  
  RESULTS
  We have developed WaveCNV, a software package to identify copy number alterations by detecting breakpoints of CNVs using translation-invariant discrete wavelet transforms and assign digitized copy numbers to each event using next-generation sequencing data. We also assign alleles specifying the chromosomal ratio following duplication/loss. We verified copy number calls using both microarray (correlation coefficient 0.97) and quantitative polymerase chain reaction (correlation coefficient 0.94) and found them to be highly concordant. We demonstrate its utility in pancreatic primary and xenograft sequencing data.
  
  
  METHODS
  Source code and executables are available at https://github.com/WaveCNV. The segmentation algorithm is implemented in MATLAB, and copy number assignment is implemented Perl.
  
  
  BACKGROUND
  lakshmi.muthuswamy@gmail.com
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Ontario Institute for Cancer Research, Toronto, ON, M5G 0A3, Canada and Department of Medical Biophysics, University of Toronto, Toronto, ON, M5G 2M9, Canada.
authors.forename: Carson
authors.initials: C
authors.lastname: Holt
authors.forename: Bojan
authors.initials: B
authors.lastname: Losic
authors.forename: Deepa
authors.initials: D
authors.lastname: Pai
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhao
authors.forename: Quang
authors.initials: Q
authors.lastname: Trinh
authors.forename: Sujata
authors.initials: S
authors.lastname: Syam
authors.forename: Niloofar
authors.initials: N
authors.lastname: Arshadi
authors.forename: Gun Ho
authors.initials: GH
authors.lastname: Jang
authors.forename: Johar
authors.initials: J
authors.lastname: Ali
authors.forename: Tim
authors.initials: T
authors.lastname: Beck
authors.forename: John
authors.initials: J
authors.lastname: McPherson
authors.forename: Lakshmi B
authors.initials: LB
authors.lastname: Muthuswamy
mesh_terms: D000465:Algorithms; D000483:Alleles; D000782:Aneuploidy; D000818:Animals; D056915:DNA Copy Number Variations; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012984:Software; D023041:Xenograft Model Antitumor Assays