Bayesian inference of selection in the Wright-Fisher diffusion model.

IF 0.8 4区 数学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Statistical Applications in Genetics and Molecular Biology Pub Date : 2018-06-06 DOI:10.1515/sagmb-2017-0046
Jeffrey J Gory, Radu Herbei, Laura S Kubatko
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引用次数: 2

Abstract

The increasing availability of population-level allele frequency data across one or more related populations necessitates the development of methods that can efficiently estimate population genetics parameters, such as the strength of selection acting on the population(s), from such data. Existing methods for this problem in the setting of the Wright-Fisher diffusion model are primarily likelihood-based, and rely on numerical approximation for likelihood computation and on bootstrapping for assessment of variability in the resulting estimates, requiring extensive computation. Recent work has provided a method for obtaining exact samples from general Wright-Fisher diffusion processes, enabling the development of methods for Bayesian estimation in this setting. We develop and implement a Bayesian method for estimating the strength of selection based on the Wright-Fisher diffusion for data sampled at a single time point. The method utilizes the latest algorithms for exact sampling to devise a Markov chain Monte Carlo procedure to draw samples from the joint posterior distribution of the selection coefficient and the allele frequencies. We demonstrate that when assumptions about the initial allele frequencies are accurate the method performs well for both simulated data and for an empirical data set on hypoxia in flies, where we find evidence for strong positive selection in a region of chromosome 2L previously identified. We discuss possible extensions of our method to the more general settings commonly encountered in practice, highlighting the advantages of Bayesian approaches to inference in this setting.

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Wright-Fisher扩散模型中贝叶斯选择推理。
在一个或多个相关种群中,种群水平等位基因频率数据的可用性越来越高,这就需要开发能够有效地估计种群遗传参数的方法,例如从这些数据中估计作用于种群的选择强度。在Wright-Fisher扩散模型的背景下,解决这个问题的现有方法主要是基于似然的,并且依赖于似然计算的数值近似和评估结果估计的可变性的自举,需要大量的计算。最近的工作提供了一种从一般Wright-Fisher扩散过程中获得精确样本的方法,从而能够在这种情况下开发贝叶斯估计方法。我们开发并实现了一种贝叶斯方法,用于估计在单个时间点采样的数据的基于Wright-Fisher扩散的选择强度。该方法利用最新的精确抽样算法,设计了马尔科夫链蒙特卡罗程序,从选择系数和等位基因频率的联合后验分布中抽取样本。我们证明,当关于初始等位基因频率的假设是准确的,该方法在模拟数据和果蝇缺氧的经验数据集上都表现良好,在这些数据集上,我们发现了在染色体2L区域中存在强阳性选择的证据。我们讨论了将我们的方法扩展到实践中经常遇到的更一般的设置的可能性,强调了贝叶斯方法在这种设置中的推断优势。
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来源期刊
Statistical Applications in Genetics and Molecular Biology
Statistical Applications in Genetics and Molecular Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-MATHEMATICAL & COMPUTATIONAL BIOLOGY
自引率
11.10%
发文量
8
期刊介绍: Statistical Applications in Genetics and Molecular Biology seeks to publish significant research on the application of statistical ideas to problems arising from computational biology. The focus of the papers should be on the relevant statistical issues but should contain a succinct description of the relevant biological problem being considered. The range of topics is wide and will include topics such as linkage mapping, association studies, gene finding and sequence alignment, protein structure prediction, design and analysis of microarray data, molecular evolution and phylogenetic trees, DNA topology, and data base search strategies. Both original research and review articles will be warmly received.
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