title: VisCap: inference and visualization of germ-line copy-number variants from targeted clinical sequencing data.
abstract: To develop and validate VisCap, a software program targeted to clinical laboratories for inference and visualization of germ-line copy-number variants (CNVs) from targeted next-generation sequencing data.
  
  
  
  VisCap calculates the fraction of overall sequence coverage assigned to genomic intervals and computes log2 ratios of these values to the median of reference samples profiled using the same test configuration. Candidate CNVs are called when log2 ratios exceed user-defined thresholds.
  
  
  
  We optimized VisCap using 14 cases with known CNVs, followed by prospective analysis of 1,104 cases referred for diagnostic DNA sequencing. To verify calls in the prospective cohort, we used droplet digital polymerase chain reaction (PCR) to confirm 10/27 candidate CNVs and 72/72 copy-neutral genomic regions scored by VisCap. We also used a genome-wide bead array to confirm the absence of CNV calls across panels applied to 10 cases. To improve specificity, we instituted a visual scoring system that enabled experienced reviewers to differentiate true-positive from false-positive calls with minimal impact on laboratory workflow.
  
  
  
  VisCap is a sensitive method for inferring CNVs from targeted sequence data from targeted gene panels. Visual scoring of data underlying CNV calls is a critical step to reduce false-positive calls for follow-up testing.Genet Med 18 7, 712-719.Genetics in Medicine (2016); 18 7, 712-719. doi:10.1038/gim.2015.156.
authors.affiliation: Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.|Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Trevor J
authors.identifier: 0000-0002-8073-5888
authors.initials: TJ
authors.lastname: Pugh
authors.affiliation: Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Boston, Massachusetts, USA.|Department of Pathology, Brigham and Women's Hospital and Massachusetts General Hospital, Boston, Massachusetts, USA.|Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Sami S
authors.identifier: 0000-0003-0927-6057
authors.initials: SS
authors.lastname: Amr
authors.affiliation: Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Boston, Massachusetts, USA.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Bowser
authors.affiliation: Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Boston, Massachusetts, USA.
authors.forename: Sivakumar
authors.initials: S
authors.lastname: Gowrisankar
authors.affiliation: Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Boston, Massachusetts, USA.
authors.forename: Elizabeth
authors.identifier: 0000-0002-3817-2145
authors.initials: E
authors.lastname: Hynes
authors.affiliation: Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Boston, Massachusetts, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Mahanta
authors.affiliation: Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Boston, Massachusetts, USA.|Department of Pathology, Brigham and Women's Hospital and Massachusetts General Hospital, Boston, Massachusetts, USA.|Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Heidi L
authors.identifier: 0000-0002-6025-0015
authors.initials: HL
authors.lastname: Rehm
authors.affiliation: Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Boston, Massachusetts, USA.|Department of Pathology, Brigham and Women's Hospital and Massachusetts General Hospital, Boston, Massachusetts, USA.|Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Birgit
authors.initials: B
authors.lastname: Funke
authors.affiliation: Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, Boston, Massachusetts, USA.|Department of Pathology, Brigham and Women's Hospital and Massachusetts General Hospital, Boston, Massachusetts, USA.|Department of Pathology, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Lebo
mesh_terms: D056915:DNA Copy Number Variations / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D018095:Germ-Line Mutation / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D057089:Pathology, Molecular; D020641:Polymorphism, Single Nucleotide; D012984:Software