PLoS ONE (Jan 2013)

Somatic point mutation calling in low cellularity tumors.

  • Karin S Kassahn,
  • Oliver Holmes,
  • Katia Nones,
  • Ann-Marie Patch,
  • David K Miller,
  • Angelika N Christ,
  • Ivon Harliwong,
  • Timothy J Bruxner,
  • Qinying Xu,
  • Matthew Anderson,
  • Scott Wood,
  • Conrad Leonard,
  • Darrin Taylor,
  • Felicity Newell,
  • Sarah Song,
  • Senel Idrisoglu,
  • Craig Nourse,
  • Ehsan Nourbakhsh,
  • Suzanne Manning,
  • Shivangi Wani,
  • Anita Steptoe,
  • Marina Pajic,
  • Mark J Cowley,
  • Mark Pinese,
  • David K Chang,
  • Anthony J Gill,
  • Amber L Johns,
  • Jianmin Wu,
  • Peter J Wilson,
  • Lynn Fink,
  • Andrew V Biankin,
  • Nicola Waddell,
  • Sean M Grimmond,
  • John V Pearson

DOI
https://doi.org/10.1371/journal.pone.0074380
Journal volume & issue
Vol. 8, no. 11
p. e74380

Abstract

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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.