title: cnvCapSeq: detecting copy number variation in long-range targeted resequencing data.
abstract: Targeted resequencing technologies have allowed for efficient and cost-effective detection of genomic variants in specific regions of interest. Although capture sequencing has been primarily used for investigating single nucleotide variants and indels, it has the potential to elucidate a broader spectrum of genetic variation, including copy number variants (CNVs). Various methods exist for detecting CNV in whole-genome and exome sequencing datasets. However, no algorithms have been specifically designed for contiguous target sequencing, despite its increasing importance in clinical and research applications. We have developed cnvCapSeq, a novel method for accurate and sensitive CNV discovery and genotyping in long-range targeted resequencing. cnvCapSeq was benchmarked using a simulated contiguous capture sequencing dataset comprising 21 genomic loci of various lengths. cnvCapSeq was shown to outperform the best existing exome CNV method by a wide margin both in terms of sensitivity (92.0 versus 48.3%) and specificity (99.8 versus 70.5%). We also applied cnvCapSeq to a real capture sequencing cohort comprising a contiguous 358 kb region that contains the Complement Factor H gene cluster. In this dataset, cnvCapSeq identified 41 samples with CNV, including two with duplications, with a genotyping accuracy of 99%, as ascertained by quantitative real-time PCR.
authors.affiliation: Department of Genomics of Common Disease, School of Public Health, Imperial College London, London W12 0NN, UK l.coin@imb.uq.edu.au.
authors.forename: Evangelos
authors.initials: E
authors.lastname: Bellos
authors.affiliation: Genome Institute of Singapore, 60 Biopolis St., 138672, Singapore.
authors.forename: Vikrant
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Genome Institute of Singapore, 60 Biopolis St., 138672, Singapore.
authors.forename: Clarabelle
authors.initials: C
authors.lastname: Lin
authors.affiliation: Institute of Medical Molecular Genetics, University of Zurich, Wagistrasse 12, 8952 Schlieren, Switzerland.
authors.forename: Jordi
authors.initials: J
authors.lastname: Maggi
authors.affiliation: Genome Institute of Singapore, 60 Biopolis St., 138672, Singapore.
authors.forename: Zai Yang
authors.initials: ZY
authors.lastname: Phua
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Center, 11 Third Hospital Avenue, 168751, Singapore Department of Ophthalmology, National University of Singapore, 1E Kent Ridge Road, 119228, Singapore.
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Center, 11 Third Hospital Avenue, 168751, Singapore Department of Ophthalmology, National University of Singapore, 1E Kent Ridge Road, 119228, Singapore.
authors.forename: Chui Ming Gemmy
authors.initials: CM
authors.lastname: Cheung
authors.affiliation: Genome Institute of Singapore, 60 Biopolis St., 138672, Singapore Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hibberd
authors.affiliation: Singapore Eye Research Institute, Singapore National Eye Center, 11 Third Hospital Avenue, 168751, Singapore Department of Ophthalmology, National University of Singapore, 1E Kent Ridge Road, 119228, Singapore.
authors.forename: Tien Yin
authors.initials: TY
authors.lastname: Wong
authors.affiliation: Department of Genomics of Common Disease, School of Public Health, Imperial College London, London W12 0NN, UK Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD 4072, Australia l.coin@imb.uq.edu.au.
authors.forename: Lachlan J M
authors.initials: LJ
authors.lastname: Coin
authors.affiliation: Genome Institute of Singapore, 60 Biopolis St., 138672, Singapore l.coin@imb.uq.edu.au.
authors.forename: Sonia
authors.initials: S
authors.lastname: Davila
mesh_terms: D000465:Algorithms; D056915:DNA Copy Number Variations; D023281:Genomics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D017422:Sequence Analysis, DNA / Q000379:methods*