VAF Aware Mode

When both the small variant caller and the CNV caller are enabled in a tumor-matched normal run, the somatic SNV results can affect the estimated purity and ploidy of the tumor sample. The somatic SNV variant allele frequencies (VAFs), as captured by the allele depth values from passing somatic SNVs, reflect the combination of tumor purity, total tumor copy number at a somatic SNV locus, and the number of tumor copies bearing the somatic allele. Clusters of somatic SNVs with similar allele depths inform the tumor model.

Somatic SNV variant allele frequency (VAF) information is especially useful when a tumor has limited copy number variation and/or CNVs are mostly subclonal, as, for instance, in many liquid tumors. Without VAF information, the estimated tumor model may be incorrect or low-confidence, leading either to wrong or filtered calls. VAF information can also help determine the presence or absence of a genome duplication even in clear, clonal CNVs.

To take advantage of VAF signal, you must run somatic CNV calling with small variant calling on tumor and matched-normal read and alignment inputs. For example, you could use the following options: --enable-vc=true --enable-cnv=true --tumor-bam-input T_BAM --bam-input N_BAM together. By default, VAF-based modeling is enabled. You can disable VAF-based modeling by setting --cnv-use-somatic-vc-vaf to false.