title: A comparative analysis of algorithms for somatic SNV detection in cancer.
abstract: BACKGROUND
  With the advent of relatively affordable high-throughput technologies, DNA sequencing of cancers is now common practice in cancer research projects and will be increasingly used in clinical practice to inform diagnosis and treatment. Somatic (cancer-only) single nucleotide variants (SNVs) are the simplest class of mutation, yet their identification in DNA sequencing data is confounded by germline polymorphisms, tumour heterogeneity and sequencing and analysis errors. Four recently published algorithms for the detection of somatic SNV sites in matched cancer-normal sequencing datasets are VarScan, SomaticSniper, JointSNVMix and Strelka. In this analysis, we apply these four SNV calling algorithms to cancer-normal Illumina exome sequencing of a chronic myeloid leukaemia (CML) patient. The candidate SNV sites returned by each algorithm are filtered to remove likely false positives, then characterized and compared to investigate the strengths and weaknesses of each SNV calling algorithm.
  
  
  RESULTS
  Comparing the candidate SNV sets returned by VarScan, SomaticSniper, JointSNVMix2 and Strelka revealed substantial differences with respect to the number and character of sites returned; the somatic probability scores assigned to the same sites; their susceptibility to various sources of noise; and their sensitivities to low-allelic-fraction candidates.
  
  
  BACKGROUND
  Data accession number SRA081939, code at http://code.google.com/p/snv-caller-review/
  
  
  BACKGROUND
  david.adelson@adelaide.edu.au
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: School of Molecular and Biomedical Science and School of Mathematical Sciences, University of Adelaide, South Australia, Australia.
authors.forename: Nicola D
authors.initials: ND
authors.lastname: Roberts
authors.forename: R Daniel
authors.initials: RD
authors.lastname: Kortschak
authors.forename: Wendy T
authors.initials: WT
authors.lastname: Parker
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Schreiber
authors.forename: Susan
authors.initials: S
authors.lastname: Branford
authors.forename: Hamish S
authors.initials: HS
authors.lastname: Scott
authors.forename: Garique
authors.initials: G
authors.lastname: Glonek
authors.forename: David L
authors.initials: DL
authors.lastname: Adelson
mesh_terms: D000465:Algorithms; D059472:Exome; D060005:Genotyping Techniques; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012984:Software