Differentiating low frequency SNVs from sequencing artifacts is the key for identifying SNVs at frequencies close to sequencing error rates. Our PSEM approach tried to push the limit toward the sequencing error rates. Based on the analyses on benchmarks from standard sequencing protocols and the given sequencing depth, we speculate the detection limit is around 0.5 % on the regions covering all exons of hundred of genes, with a total size up to millions of bases. However, with high accuracy sequencing protocols, such as duplex sequencing [24] and ultra-deep target enrichment assay [25], the researchers reported identification of SNVs around 0.1 % on a single gene scale. Despite the promising results, more efforts to make such protocols applicable on larger regions are required for broader applications.
