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Accurate Computation of Likelihoods in the Coalescent with Recombination Via Parsimony

机译:通过简约性进行重组的合并中的似然性的精确计算

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Understanding the variation of recombination rates across a given genome is crucial for disease gene mapping and for detecting signatures of selection, to name just a couple of applications. A widely-used method of estimating recombination rates is the maximum likelihood approach, and the problem of accurately computing likelihoods in the coalescent with recombination has received much attention in the past. A variety of sampling and approximation methods have been proposed, but no single method seems to perform consistently better than the rest, and there still is great value in developing better statistical methods for accurately computing likelihoods. So far, with the exception of some two-locus models, it has remained unknown how the true likelihood exactly behaves as a function of model parameters, or how close estimated likelihoods are to the true likelihood. In this paper, we develop a deterministic, parsimony-based method of accurately computing the likelihood for multi-locus input data of moderate size. We first find the set of all ancestral configurations (ACs) that occur in evolutionary histories with at most k crossover recombinations. Then, we compute the likelihood by summing over all evolutionary histories that can be constructed only using the ACs in that set. We allow for an arbitrary number of crossing over, coalescent and mutation events in a history, as long as the transitions stay within that restricted set of ACs. For given parameter values, by gradually increasing the bound k until the likelihood stabilizes, we can obtain an accurate estimate of the likelihood. At least for moderate crossover rates, the algorithm-based method described here opens up a new window of opportunities for testing and fine-tuning statistical methods for computing likelihoods.
机译:仅举例说明几个应用,了解给定基因组中重组率的变化对于疾病基因作图和检测选择标记至关重要。估计重组率的一种广泛使用的方法是最大似然法,并且在过去的重组中,在合并中准确计算似然性的问题已引起广泛关注。已经提出了多种采样和逼近方法,但是似乎没有一种方法比其他方法具有始终如一的性能,因此,开发更好的统计方法以准确计算似然率仍然具有重要的价值。到目前为止,除了某些两位置模型外,尚不清楚真实可能性如何准确地表现为模型参数的函数,或者估计的可能性与真实可能性有多接近。在本文中,我们开发了一种基于确定性的,基于简约性的方法,可以准确地计算中等大小的多位置输入数据的可能性。我们首先找到在进化史中出现的所有祖先构型(AC)的集合,最多具有k个交叉重组。然后,我们通过汇总仅可使用该集合中的AC构造的所有进化历史来计算可能性。只要转换保持在受限的AC范围内,我们就可以允许历史中任意数量的交叉,合并和突变事件。对于给定的参数值,通过逐渐增加边界k直到似然性稳定,我们可以获得似然性的准确估计。至少对于适中的交叉速率,此处描述的基于算法的方法为测试和微调统计方法以计算可能性开辟了新的机会。

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