Gerard David
Department of Mathematics and Statistics, American University, Washington DC, USA.
Mol Ecol Resour. 2023 Nov;23(8):1812-1822. doi: 10.1111/1755-0998.13856. Epub 2023 Aug 14.
Hardy-Weinberg proportions (HWP) are often explored to evaluate the assumption of random mating. However, in autopolyploids, organisms with more than two sets of homologous chromosomes, HWP and random mating are different hypotheses that require different statistical testing approaches. Currently, the only available methods to test for random mating in autopolyploids (i) heavily rely on asymptotic approximations and (ii) assume genotypes are known, ignoring genotype uncertainty. Furthermore, these approaches are all frequentist, and so do not carry the benefits of Bayesian analysis, including ease of interpretability, incorporation of prior information, and consistency under the null. Here, we present Bayesian approaches to test for random mating, bringing the benefits of Bayesian analysis to this problem. Our Bayesian methods also (i) do not rely on asymptotic approximations, being appropriate for small sample sizes, and (ii) optionally account for genotype uncertainty via genotype likelihoods. We validate our methods in simulations and demonstrate on two real datasets how testing for random mating is more useful for detecting genotyping errors than testing for HWP (in a natural population) and testing for Mendelian segregation (in an experimental S1 population). Our methods are implemented in Version 2.0.2 of the hwep R package on the Comprehensive R Archive Network https://cran.r-project.org/package=hwep.
哈迪-温伯格比例(HWP)常被用于评估随机交配的假设。然而,在同源多倍体(即具有两组以上同源染色体的生物体)中,HWP和随机交配是不同的假设,需要不同的统计检验方法。目前,用于检测同源多倍体中随机交配的唯一可用方法:(i)严重依赖渐近近似;(ii)假设基因型已知,而忽略了基因型的不确定性。此外,这些方法都是频率主义的,因此没有贝叶斯分析的优势,包括易于解释、纳入先验信息以及在原假设下的一致性。在此,我们提出用于检测随机交配的贝叶斯方法,将贝叶斯分析的优势应用于这个问题。我们的贝叶斯方法还具有以下特点:(i)不依赖渐近近似,适用于小样本量;(ii)可通过基因型似然性选择性地考虑基因型不确定性。我们在模拟中验证了我们的方法,并在两个真实数据集上证明,与检测HWP(在自然种群中)和孟德尔分离(在实验S1种群中)相比,检测随机交配对于检测基因分型错误更有用。我们的方法在综合R存档网络https://cran.r-project.org/package=hwep上的hwep R包2.0.2版本中实现。