RAREsim: A simulation method for very rare genetic variants.
RAREsim: A simulation method for very rare genetic variants.
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RAREsim：一种针对非常罕见的遗传变异的模拟方法。
DOI：
10.1016/j.ajhg.2022.02.009
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发表时间：
2022
影响因子：
9.8
通讯作者：
Hendricks,AudreyE
中科院分区：
文献类型：
--
作者：
Null,Megan;Dupuis,Josée;Sheinidashtegol,Pezhman;Layer,RyanM;Gignoux,ChristopherR;Hendricks,AudreyE
稀有变异关联的鉴定对于复杂性状和疾病的遗传结构的全面表征至关重要。在这个过程中，关键是在模拟数据中评估新方法，这些模拟数据反映了真实的数据中罕见变异和单倍型结构的分布。此外，导入真实变异注释可实现对方法的计算机比较，例如罕见变异关联测试和多基因评分方法，这些方法侧重于假定的因果变异。现有的模拟方法要么不能采用实变注释，要么严重低估或高估单例和双例的数量，从而降低了将模拟结果推广到真实的研究的能力。我们提出了RAREsim，一个灵活和准确的稀有变量模拟算法。RAREsim使用源自真实的测序数据的参数和单倍型，有效模拟预期的变异分布，并实现真实变异注释。我们强调了RAREsim在不同遗传区域、样本量、祖先和变体类别中的实用性。
Identification of rare-variant associations is crucial to full characterization of the genetic architecture of complex traits and diseases. Essential in this process is the evaluation of novel methods in simulated data that mirror the distribution of rare variants and haplotype structure in real data. Additionally, importing real-variant annotation enablesin silicocomparison of methods, such as rare-variant association tests and polygenic scoring methods, that focus on putative causal variants. Existing simulation methods are either unable to employ real-variant annotation or severely under- or overestimate the number of singletons and doubletons, thereby reducing the ability to generalize simulation results to real studies. We present RAREsim, a flexible and accurate rare-variant simulation algorithm. Using parameters and haplotypes derived from real sequencing data, RAREsim efficiently simulates the expected variant distribution and enables real-variant annotations. We highlight RAREsim's utility across various genetic regions, sample sizes, ancestries, and variant classes.