title: SynthEx: a synthetic-normal-based DNA sequencing tool for copy number alteration detection and tumor heterogeneity profiling.
abstract: Changes in the quantity of genetic material, known as somatic copy number alterations (CNAs), can drive tumorigenesis. Many methods exist for assessing CNAs using microarrays, but considerable technical issues limit current CNA calling based upon DNA sequencing. We present SynthEx, a novel tool for detecting CNAs from whole exome and genome sequencing. SynthEx utilizes a "synthetic-normal" strategy to overcome technical and financial issues. In terms of accuracy and precision, SynthEx is highly comparable to array-based methods and outperforms sequencing-based CNA detection tools. SynthEx robustly identifies CNAs using sequencing data without the additional costs associated with matched normal specimens.
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Curriculum in Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, NC, 27599, USA.|Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Grace O
authors.initials: GO
authors.lastname: Silva
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Marni B
authors.initials: MB
authors.lastname: Siegel
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Lisle E
authors.initials: LE
authors.lastname: Mose
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Joel S
authors.initials: JS
authors.lastname: Parker
authors.affiliation: Public Health Division, Fred Hutchison Cancer Research Center, Seattle, WA, 98109, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.affiliation: Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Curriculum in Bioinformatics and Computational Biology, University of North Carolina, Chapel Hill, NC, 27599, USA.|Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, 27599, USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.affiliation: Section of Genetic Medicine, Department of Medicine, The University of Chicago, 900 East 57th Street, KCBD 3220A, Chicago, IL, 60637, USA. mengjiechen@uchicago.edu.
authors.forename: Mengjie
authors.identifier: 0000-0003-1579-087X
authors.initials: M
authors.lastname: Chen
mesh_terms: D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D056915:DNA Copy Number Variations; D059472:Exome; D005091:Exons; D018628:Gene Dosage; D020869:Gene Expression Profiling / Q000379:methods; D018740:Genetic Heterogeneity; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA / Q000379:methods; D012984:Software
keywords: Breast cancer; Copy number; Sequencing; Synthetic normal; The Cancer Genome Atlas; Whole exome; Whole genome