Ultradeep analysis of tumor heterogeneity in regions of somatic hypermutation

Tumor heterogeneity is of growing importance in the treatment of cancers. Mutational hot spots are prime locations for determining number and proportions of low variant allele frequency (VAF) tumor subclones by next generation sequencing. Low VAF detection is complicated by poor mapping efficiency in regions with high mutation density. Our Deep-Drilling with iterative Mapping (DDiMAP) method retains variant allele patterns to aid in single nucleotide variation detection and generation of additional reference alleles, with remapping increasing coverage of highly mutated regions to capture data critical to heterogeneity analysis and enhancing sensitivity. DDiMAP outputs variant patterns with frequencies, enabling rapid phylogenetic analysis of ongoing mutation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13073-015-0147-1) contains supplementary material, which is available to authorized users.