药物代谢酶基因的全基因组测序与临床基因分型比较
Comparison of genome sequencing and clinical genotyping for pharmacogenes.
作者信息
Yang W, Wu G, Broeckel U, Smith C A, Turner V, Haidar C E, Wang S, Carter R, Karol S E, Neale G, Crews K R, Yang J J, Mullighan C G, Downing J R, Evans W E, Relling M V
机构信息
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Department of Computational Biology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
出版信息
Clin Pharmacol Ther. 2016 Oct;100(4):380-8. doi: 10.1002/cpt.411. Epub 2016 Aug 18.
We compared whole exome sequencing (WES, n = 176 patients) and whole genome sequencing (WGS, n = 68) and clinical genotyping (DMET array-based approach) for interrogating 13 genes with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. We focused on 127 CPIC important variants: 103 single nucleotide variations (SNV), 21 insertion/deletions (Indel), HLA-B alleles, and two CYP2D6 structural variations. WES and WGS provided interrogation of nonoverlapping sets of 115 SNV/Indels with call rate >98%. Among 68 loci interrogated by both WES and DMET, 64 loci (94.1%, confidence interval [CI]: 85.6-98.4%) showed no discrepant genotyping calls. Among 66 loci interrogated by both WGS and DMET, 63 loci (95.5%, CI: 87.2-99.0%) showed no discrepant genotyping calls. In conclusion, even without optimization to interrogate pharmacogenetic variants, WES and WGS displayed potential to provide reliable interrogation of most pharmacogenes and further validation of genome sequencing in a clinical lab setting is warranted.
我们比较了全外显子组测序（WES，176例患者）、全基因组测序（WGS，68例）以及基于临床药物基因组学实施联盟（CPIC）指南对13个基因进行检测的临床基因分型（基于DMET芯片的方法）。我们重点关注了127个CPIC重要变异：103个单核苷酸变异（SNV）、21个插入/缺失（Indel）、HLA - B等位基因以及两个CYP2D6结构变异。WES和WGS对115个SNV/Indel的非重叠集合进行检测，检出率>98%。在WES和DMET都检测的68个位点中，64个位点（94.1%，置信区间[CI]：85.6 - 98.4%）的基因分型结果无差异。在WGS和DMET都检测的66个位点中，63个位点（95.5%，CI：87.2 - 99.0%）的基因分型结果无差异。总之，即使未针对药物遗传变异检测进行优化，WES和WGS仍显示出对大多数药物基因进行可靠检测的潜力，在临床实验室环境中对基因组测序进行进一步验证是有必要的。
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