一个多样化的祖先匹配的参考面板增加了在代表性不足的人群中基因型归算的准确性
John Mauleekoonphairoj1,2, Sissades Tongsima3, Apichai Khongphatthanayothin1,4,5
1Center of Excellence in Arrhythmia Research, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Scientific reports
|July 31, 2023
概括
在全基因组关联研究中,选择正确的参考小组对于准确的变异归因至关重要. 基因组亚洲100K小组证明了泰国人口的卓越归算准确性,即使对于罕见的变异.
科学领域:
- 基因组学就是基因组学.
- 人口遗传学 人口遗传学
- 生物信息学是一种生物信息学.
背景情况:
- 变异归算对于全基因组关联研究 (GWAS) 至关重要,以使用参考面板推断未观察到的基因型.
- 现有的公共参考面板在尺寸,测序深度和人口代表性方面各不相同.
- 对代表人数不足的参考小组的绩效评估是有限的.
研究的目的:
- 为了比较泰国人口的主要公共参考面板 (1000 Genomes,HRC,GenomeAsia 100K,TOPMed) 的归算性能.
- 对高深度全基因组测序数据进行基因型产量和归算准确性的评估.
- 确定最佳的参考小组,用于在代表性不足的人口中归因遗传数据.
主要方法:
- 对四个公共参考小组进行了比较分析:1000个基因组项目,哈普洛型参考联盟 (HRC),GenomeAsia 100K和Trans-Omics for Precision Medicine (TOPMed).
- 使用每个参考小组计算泰国人口样本.
- 基因型对应率的评估,通过将假定基因型与高深度全基因组测序数据进行比较.
- 对常见和罕见变异的归算精度的评估.
主要成果:
- 精准医学的Trans-Omics (TOPMed) 专家小组提供了最大数量的归算变体 (大约2.71亿).
- 基因组亚洲100K小组实现了最高的归算准确度,基因型一致率中位数为0.97.
- 基因组亚洲100K也显示了罕见变异的最佳准确性,尽管整体罕见变异归算准确性低于常见变异.
- 基因组亚洲100K的卓越表现归因于其多样化的人口代表性,包括与泰国队列遗传相似的群体.
结论:
- 参考小组的选择显著影响变异归算的准确性,特别是在代表性不足的人群中.
- 建议使用GenomeAsia 100K小组对泰国和遗传上相似的人口进行准确的归算.
- 增加对不同种群的测序和纳入参考小组对于推进代表性不足群体的基因组研究至关重要.
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