title: SMASH, a fragmentation and sequencing method for genomic copy number analysis.
abstract: Copy number variants (CNVs) underlie a significant amount of genetic diversity and disease. CNVs can be detected by a number of means, including chromosomal microarray analysis (CMA) and whole-genome sequencing (WGS), but these approaches suffer from either limited resolution (CMA) or are highly expensive for routine screening (both CMA and WGS). As an alternative, we have developed a next-generation sequencing-based method for CNV analysis termed SMASH, for short multiply aggregated sequence homologies. SMASH utilizes random fragmentation of input genomic DNA to create chimeric sequence reads, from which multiple mappable tags can be parsed using maximal almost-unique matches (MAMs). The SMASH tags are then binned and segmented, generating a profile of genomic copy number at the desired resolution. Because fewer reads are necessary relative to WGS to give accurate CNV data, SMASH libraries can be highly multiplexed, allowing large numbers of individuals to be analyzed at low cost. Increased genomic resolution can be achieved by sequencing to higher depth.
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Zihua
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Andrews
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Jude
authors.initials: J
authors.lastname: Kendall
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Beicong
authors.initials: B
authors.lastname: Ma
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Inessa
authors.initials: I
authors.lastname: Hakker
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Rodgers
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Ronemus
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wigler
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Levy
mesh_terms: D045744:Cell Line, Tumor; D019295:Computational Biology; D056915:DNA Copy Number Variations; D005260:Female; D018628:Gene Dosage; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D017422:Sequence Analysis, DNA; D012984:Software