BACKGROUND: High-throughput sequencing is rapidly becoming common practice in 
clinical diagnosis and cancer research. Many algorithms have been developed for 
somatic single nucleotide variant (SNV) detection in matched tumor-normal DNA 
sequencing. Although numerous studies have compared the performance of various 
algorithms on exome data, there has not yet been a systematic evaluation using 
PCR-enriched amplicon data with a range of variant allele fractions. The 
recently developed gold standard variant set for the reference individual 
NA12878 by the NIST-led "Genome in a Bottle" Consortium (NIST-GIAB) provides a 
good resource to evaluate admixtures with various SNV fractions.
RESULTS: Using the NIST-GIAB gold standard, we compared the performance of five 
popular somatic SNV calling algorithms (GATK UnifiedGenotyper followed by simple 
subtraction, MuTect, Strelka, SomaticSniper and VarScan2) for matched 
tumor-normal amplicon and exome sequencing data.
CONCLUSIONS: We demonstrated that the five commonly used somatic SNV calling 
methods are applicable to both targeted amplicon and exome sequencing data. 
However, the sensitivities of these methods vary based on the allelic fraction 
of the mutation in the tumor sample. Our analysis can assist researchers in 
choosing a somatic SNV calling method suitable for their specific needs.