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在无限多位点模型中计算具有多次碰撞的合并过程的似然性。

Computing likelihoods for coalescents with multiple collisions in the infinitely many sites model.

作者信息

Birkner Matthias, Blath Jochen

机构信息

Weierstrass-Institut für Angewandte Analysis und Stochastik, Mohrenstrasse 39, 10117 Berlin, Germany.

出版信息

J Math Biol. 2008 Sep;57(3):435-65. doi: 10.1007/s00285-008-0170-6. Epub 2008 Mar 18.

Abstract

One of the central problems in mathematical genetics is the inference of evolutionary parameters of a population (such as the mutation rate) based on the observed genetic types in a finite DNA sample. If the population model under consideration is in the domain of attraction of the classical Fleming-Viot process, such as the Wright-Fisher- or the Moran model, then the standard means to describe its genealogy is Kingman's coalescent. For this coalescent process, powerful inference methods are well-established. An important feature of the above class of models is, roughly speaking, that the number of offspring of each individual is small when compared to the total population size, and hence all ancestral collisions are binary only. Recently, more general population models have been studied, in particular in the domain of attraction of so-called generalised Lambda-Fleming-Viot processes, as well as their (dual) genealogies, given by the so-called Lambda-coalescents, which allow multiple collisions. Moreover, Eldon and Wakeley (Genetics 172:2621-2633, 2006) provide evidence that such more general coalescents might actually be more adequate to describe real populations with extreme reproductive behaviour, in particular many marine species. In this paper, we extend methods of Ethier and Griffiths (Ann Probab 15(2):515-545, 1987) and Griffiths and Tavaré (Theor Pop Biol 46:131-159, 1994a, Stat Sci 9:307-319, 1994b, Philos Trans Roy Soc Lond Ser B 344:403-410, 1994c, Math Biosci 12:77-98, 1995) to obtain a likelihood based inference method for general Lambda-coalescents. In particular, we obtain a method to compute (approximate) likelihood surfaces for the observed type probabilities of a given sample. We argue that within the (vast) family of Lambda-coalescents, the parametrisable sub-family of Beta(2 - alpha, alpha)-coalescents, where alpha in (1, 2], are of particular relevance. We illustrate our method using simulated datasets, thus obtaining maximum-likelihood estimators of mutation and demographic parameters.

摘要

数理遗传学的核心问题之一是基于有限DNA样本中观察到的基因类型来推断种群的进化参数(如突变率)。如果所考虑的种群模型属于经典弗莱明 - 维奥特过程的吸引域,例如赖特 - 费希尔模型或莫兰模型,那么描述其系谱的标准方法是金曼合并过程。对于这个合并过程,强大的推断方法已经确立。大致来说,上述这类模型的一个重要特征是,与总人口规模相比,每个个体的后代数量较少,因此所有祖先碰撞都是二元的。最近,人们研究了更一般的种群模型,特别是在所谓广义拉姆达 - 弗莱明 - 维奥特过程的吸引域内,以及由所谓拉姆达合并过程给出的它们的(对偶)系谱,该过程允许多重碰撞。此外,埃尔登和韦克利(《遗传学》172:2621 - 2633,2006年)提供的证据表明,这种更一般的合并过程可能实际上更适合描述具有极端繁殖行为的真实种群,特别是许多海洋物种。在本文中,我们扩展了埃西尔和格里菲思(《概率论年刊》15(2):515 - 545,1987年)以及格里菲思和塔瓦雷(《理论种群生物学》46:131 - 159,1994a;《统计科学》9:307 - 319,1994b;《伦敦皇家学会哲学学报B辑》344:403 - 410,1994c;《数学生物科学》12:77 - 98,1995年)的方法,以获得基于似然的广义拉姆达合并过程的推断方法。特别是,我们得到了一种计算给定样本观察类型概率的(近似)似然曲面的方法。我们认为在(庞大的)拉姆达合并过程家族中,参数可化的β(2 - α, α)合并过程子家族(其中α∈(1, 2])具有特别的相关性。我们使用模拟数据集来说明我们的方法,从而获得突变和人口统计参数的最大似然估计值。

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