Fig. 1

Concept and workflow of the approach. a VAF distribution of HETs at 30× sequencing coverage in three cases: Bulk sample, uniformly amplified cell, and un-uniformly amplified cell. The distribution from bulk shows a peak around 50%, which is expected. Then we have a single cell sequenced at 30× with good amplification. The allele frequency plot still has a peak around 50%, but not as sharp as the bulk sample. The last example is a single cell also sequenced at 30× but with non-uniform amplification. b Conceptual description of the approach. First, SNPs are phased. The reads supporting the SNPs are divided into two haplotypes, named maternal and paternal, although the exact origin of each haplotype is unknowns. With less than 1 read supporting each SNP (coverage < 1×), multiple SNPs are merged to form a SNP unit. Reads supporting SNPs within the SNP unit from only one haplotype are used to calculate the allele frequency over that SNP unit. The allele frequency plot for high coverage data closely resembles the one from shallow coverage data