title: CONTRA: copy number analysis for targeted resequencing.
abstract: BACKGROUND
  In light of the increasing adoption of targeted resequencing (TR) as a cost-effective strategy to identify disease-causing variants, a robust method for copy number variation (CNV) analysis is needed to maximize the value of this promising technology.
  
  
  RESULTS
  We present a method for CNV detection for TR data, including whole-exome capture data. Our method calls copy number gains and losses for each target region based on normalized depth of coverage. Our key strategies include the use of base-level log-ratios to remove GC-content bias, correction for an imbalanced library size effect on log-ratios, and the estimation of log-ratio variations via binning and interpolation. Our methods are made available via CONTRA (COpy Number Targeted Resequencing Analysis), a software package that takes standard alignment formats (BAM/SAM) and outputs in variant call format (VCF4.0), for easy integration with other next-generation sequencing analysis packages. We assessed our methods using samples from seven different target enrichment assays, and evaluated our results using simulated data and real germline data with known CNV genotypes.
authors.affiliation: Bioinformatics Core Facility, Peter MacCallum Cancer Centre, VIC 3002, Australia. Jason.Li@petermac.org
authors.forename: Jason
authors.initials: J
authors.lastname: Li
authors.forename: Richard
authors.initials: R
authors.lastname: Lupat
authors.forename: Kaushalya C
authors.initials: KC
authors.lastname: Amarasinghe
authors.forename: Ella R
authors.initials: ER
authors.lastname: Thompson
authors.forename: Maria A
authors.initials: MA
authors.lastname: Doyle
authors.forename: Georgina L
authors.initials: GL
authors.lastname: Ryland
authors.forename: Richard W
authors.initials: RW
authors.lastname: Tothill
authors.forename: Saman K
authors.initials: SK
authors.lastname: Halgamuge
authors.forename: Ian G
authors.initials: IG
authors.lastname: Campbell
authors.forename: Kylie L
authors.initials: KL
authors.lastname: Gorringe
mesh_terms: D000818:Animals; D003198:Computer Simulation; D056915:DNA Copy Number Variations; D059472:Exome; D060148:HapMap Project; D006801:Humans; D051379:Mice; D017422:Sequence Analysis, DNA; D012984:Software