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Robust Estimation of Local Genetic Ancestry in Admixed Populations Using a Nonparametric Bayesian Approach

机译:使用非参数贝叶斯方法对混合种群中局部遗传祖先的鲁棒估计

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We present a new haplotype-based approach for inferring local genetic ancestry of individuals in an admixed population. Most existing approaches for local ancestry estimation ignore the latent genetic relatedness between ancestral populations and treat them as independent. In this article, we exploit such information by building an inheritance model that describes both the ancestral populations and the admixed population jointly in a unified framework. Based on an assumption that the common hypothetical founder haplotypes give rise to both the ancestral and the admixed population haplotypes, we employ an infinite hidden Markov model to characterize each ancestral population and further extend it to generate the admixed population. Through an effective utilization of the population structural information under a principled nonparametric Bayesian framework, the resulting model is significantly less sensitive to the choice and the amount of training data for ancestral populations than state-of-the-art algorithms. We also improve the robustness under deviation from common modeling assumptions by incorporating population-specific scale parameters that allow variable recombination rates in different populations. Our method is applicable to an admixed population from an arbitrary number of ancestral populations and also performs competitively in terms of spurious ancestry proportions under a general multiway admixture assumption. We validate the proposed method by simulation under various admixing scenarios and present empirical analysis results from a worldwide-distributed dataset from the Human Genome Diversity Project.
机译:我们提出了一种新的基于单倍型的方法来推断混合人群中个体的局部遗传谱系。大多数现有的本地祖先估计方法都忽略了祖先群体之间潜在的遗传相关性,并将其视为独立的。在本文中,我们通过建立一个继承模型来利用此类信息,该继承模型在统一框架中共同描述祖先种群和混合种群。基于常见的假设创始人单倍型会同时产生祖先和混合种群单倍型的假设,我们采用无限隐马尔可夫模型来刻画每个祖先种群的特征,并进一步扩展它以生成混合种群。通过在有原则的非参数贝叶斯框架下有效地利用人口结构信息,所产生的模型对祖先人口的选择和训练数据的数量的敏感度明显低于最新算法。我们还通过结合特定于人群的比例参数来提高在偏离通用建模假设的情况下的鲁棒性,这些参数允许不同人群中的可变重组率。我们的方法适用于任意数量的祖先种群的混合种群,并且在一般的多路混合假设下,在伪造祖先比例方面也具有竞争力。我们通过在各种混合场景下进行仿真来验证所提出的方法,并从人类基因组多样性计划的全球分布数据集中提供实证分析结果。

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