Fig. 1

Overview of VAF phasing method. a The left panel illustrates two heterozygous germline SNVs in trans phase with the chromosome carrying SNV1 somatically amplified. In the normal sample, both SNVs have a VAF of 0.5. In the tumor sample, SNV1 is overrepresented in the sequence data (VAF = 0.75) and SNV2 is underrepresented (VAF = 0.25). The difference in VAF between the tumor and normal sample, which we refer to as Δ VAF, indicates that the VAF of SNV1 is increased (Δ VAF = 0.25) and that the VAF of SNV2 is decreased (Δ VAF = -0.25) in the somatic sample. For a pair of variants, somatic changes VAF in opposite directions suggest that the variants lie on different homologous chromosomes. b The right panel illustrates two heterozygous germline SNVs in cis phase with the chromosome carrying both SNV1 and SNV2 somatically amplified. In this case, both variants have an increased VAF (Δ VAF = 0.25). For a pair of variants, somatic changes VAF in the same direction suggest that the variants lie on the same homologous chromosome. c The VAF phasing pipeline has two steps: a Fisher’s exact test to identify sites with significant Δ VAF, and circular binary segmentation (CBS) on Δ VAF values to identify SCNA regions