Calling Star Alleles With Stargazer in 28 Pharmacogenes With Whole Genome Sequences
Calling Star Alleles With Stargazer in 28 Pharmacogenes With Whole Genome Sequences
复制标题
DOI：
10.1002/cpt.1552
复制
发表时间：
2019-07-26
影响因子：
6.7
通讯作者：
Nickerson, Deborah A.
中科院分区：
文献类型：
--
作者：
Lee, Seung-been;Wheeler, Marsha M.;Nickerson, Deborah A.
药物基因组酶活性的变异由星星等位基因（单倍型）定义，包括单核苷酸变异、小插入-缺失和大结构变异。我们最近开发了Stargazer，这是一种新一代基于测序的工具，用于调用临床上重要的CYP 2D 6基因的星星等位基因。在这里，我们提出的实用程序扩展Stargazer调用星星等位基因的28个药物基因组全基因组测序（WGS）数据。我们将Stargazer应用于来自遗传检测参考材料协调计划（GeT-RM）的70个不同种族样本的WGS数据。使用多种药物遗传学检测试验，通过GeT-RM对这些参比样品进行了广泛表征。在所有28个基因中，Stargazer回忆起100%的星星等位基因（N = 92）存在于GeT-RM的共有基因型（N = 1,559）中。Stargazer还检测到了GeT-RM以前没有报道过的星星等位基因，包括复杂的结构变体。我们的研究结果表明，结合WGS数据和Stargazer，可以对人类基因组中的药物基因进行自动、准确和全面的基因分型。
Variation in the enzymatic activity of pharmacogenes is defined by star alleles (haplotypes) comprised of single-nucleotide variants, small insertion-deletions, and large structural variants. We recently developed Stargazer, a next-generation sequencing-based tool to call star alleles for the clinically important CYP2D6 gene. Here, we present the utility of extending Stargazer to call star alleles for 28 pharmacogenes using whole genome sequencing (WGS) data. We applied Stargazer to WGS data from 70 ethnically diverse samples from the Genetic Testing Reference Materials Coordination Program (GeT-RM). These reference samples were extensively characterized by GeT-RM using multiple pharmacogenetic testing assays. In all 28 genes, Stargazer recalled 100% of star alleles (N = 92) present in GeT-RM's consensus genotypes (N = 1,559). Stargazer also detected star alleles not previously reported by GeT-RM, including complex structural variants. Our results demonstrate that combining WGS data and Stargazer enables automated, accurate, and comprehensive genotyping of pharmacogenes in the human genome.