title: Somatic point mutation calling in low cellularity tumors.
abstract: Somatic mutation calling from next-generation sequencing data remains a challenge due to the difficulties of distinguishing true somatic events from artifacts arising from PCR, sequencing errors or mis-mapping. Tumor cellularity or purity, sub-clonality and copy number changes also confound the identification of true somatic events against a background of germline variants. We have developed a heuristic strategy and software (http://www.qcmg.org/bioinformatics/qsnp/) for somatic mutation calling in samples with low tumor content and we show the superior sensitivity and precision of our approach using a previously sequenced cell line, a series of tumor/normal admixtures, and 3,253 putative somatic SNVs verified on an orthogonal platform.
authors.affiliation: Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Karin S
authors.initials: KS
authors.lastname: Kassahn
authors.forename: Oliver
authors.initials: O
authors.lastname: Holmes
authors.forename: Katia
authors.initials: K
authors.lastname: Nones
authors.forename: Ann-Marie
authors.initials: AM
authors.lastname: Patch
authors.forename: David K
authors.initials: DK
authors.lastname: Miller
authors.forename: Angelika N
authors.initials: AN
authors.lastname: Christ
authors.forename: Ivon
authors.initials: I
authors.lastname: Harliwong
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Bruxner
authors.forename: Qinying
authors.initials: Q
authors.lastname: Xu
authors.forename: Matthew
authors.initials: M
authors.lastname: Anderson
authors.forename: Scott
authors.initials: S
authors.lastname: Wood
authors.forename: Conrad
authors.initials: C
authors.lastname: Leonard
authors.forename: Darrin
authors.initials: D
authors.lastname: Taylor
authors.forename: Felicity
authors.initials: F
authors.lastname: Newell
authors.forename: Sarah
authors.initials: S
authors.lastname: Song
authors.forename: Senel
authors.initials: S
authors.lastname: Idrisoglu
authors.forename: Craig
authors.initials: C
authors.lastname: Nourse
authors.forename: Ehsan
authors.initials: E
authors.lastname: Nourbakhsh
authors.forename: Suzanne
authors.initials: S
authors.lastname: Manning
authors.forename: Shivangi
authors.initials: S
authors.lastname: Wani
authors.forename: Anita
authors.initials: A
authors.lastname: Steptoe
authors.forename: Marina
authors.initials: M
authors.lastname: Pajic
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Cowley
authors.forename: Mark
authors.initials: M
authors.lastname: Pinese
authors.forename: David K
authors.initials: DK
authors.lastname: Chang
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Gill
authors.forename: Amber L
authors.initials: AL
authors.lastname: Johns
authors.forename: Jianmin
authors.initials: J
authors.lastname: Wu
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wilson
authors.forename: Lynn
authors.initials: L
authors.lastname: Fink
authors.forename: Andrew V
authors.initials: AV
authors.lastname: Biankin
authors.forename: Nicola
authors.initials: N
authors.lastname: Waddell
authors.forename: Sean M
authors.initials: SM
authors.lastname: Grimmond
authors.forename: John V
authors.initials: JV
authors.lastname: Pearson
mesh_terms: D019295:Computational Biology; D056915:DNA Copy Number Variations / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D017354:Point Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D012984:Software