Fig 1.
Major design strategies used to construct ClinPharmSeq.
Table 1.
Summary of 59 pharmacogenes targeted by ClinPharmSeq and their mean sequencing coverage for Set 1 and Set 2.
Fig 2.
Variant call concordance between WGS and ClinPharmSeq.
Table 2.
Star alleles assessed by PyPGx’s analysis of whole genome sequencing and ClinPharmSeq data.
Fig 3.
Concordance of diplotype calls for 27 pharmacogenes between WGS, ClinPharmSeq, and previous studies.
Fig 4.
Examples of SVs detected with WGS and ClinPharmSeq.
WGS data are shown in the left panels (A, C, and E) while ClinPharmSeq data are shown in the right panels (B, C, and D). Each panel contains a copy number profile and an allele fraction profile created by PyPGx. (A-B) CYP2B7/CYP2B6 hybrid in African sample NA19178 with a CYP2B6*6/*29 diplotype. (C-D) Gene duplication in African sample NA18861 with a CYP2A6*1x2/*25 diplotype. (E-F) Complex CYP2D6/CYP2D7 hybrid in East Asian sample NA18526 with a CYP2D6*1/*36x2+*10 diplotype.
Fig 5.
Examples of diplotype discrepancy caused by difference in SV interpretation between this study and previous publications.
WGS data are shown in the left panels (A, C, and E) while ClinPharmSeq data are shown in the right panels (B, C, and D). Each panel contains a copy number profile and an allele fraction profile created by PyPGx. (A-B) East Asian sample NA18540 was previously identified to have three CYP2D6 gene copies in total with a CYP2D6(*36+)10/*41 diplotype, but this study identified four gene copies with a CYP2D6*36x2+*10/*41 diplotype. (C-D) African sample NA19908 was previously suggested to have a CYP2E1*7x2/*7x2 diplotype (i.e. allele fraction ratio of 2:2), while this study found evidence of a CYP2E1*7/*7x3 diplotype (i.e. allele fraction ratio of 1:3). (E-F) East Asian sample HG00436 was previously genotyped to have a combination of one known SV (CYP2A6*4) and one novel SV (CYP2A6*1+*S6), while in this study PyPGx produced an ‘Indeterminate’ diplotype call because it could also be just one novel SV, which would be a more parsimonious explanation.
Fig 6.
Distribution of predicted phenotypes for nine pharmacogenes with a CPIC genotype-phenotype table.
WGS data (N = 70) is shown as a representative example.