Somatic Point Mutation Calling in Low Cellularity Tumors

<div><p>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 (<a href="http://www.qcmg.org/bioinformatics/qsnp/" target="_blank">http://www.qcmg.org/bioinformatics/qsnp/</a>) 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.</p>