Details of the Stargazer genotyping pipeline have been described previously43. In brief, SNVs and indels in CYP2D6 were assessed from a VCF file generated using GATK-HaplotypeCaller89. The VCF file was phased using the program Beagle90 and the 1000 Genomes Project haplotype reference panel. Phased SNVs and indels were then matched to star alleles. In parallel, read depth was calculated from BAM files using GATK-DepthOfCoverage89. Read depth was converted to copy number by performing intra-sample normalization43. After normalization, structural variants were assessed by testing all possible pairwise combinations of pre-defined copy number profiles against the observed copy number profile of the sample. For new SVs, breakpoints were statistically inferred using changepoint91. Information regarding new SVs was stored and used to identify subsequent SVs in copy number profiles. Output data included individual diplotypes, copy number plots and a VCF of SNVs and indels that were not used to define star alleles.
