Cosi2: an efficient simulator of exact and approximate coalescent with selection
Cosi2: an efficient simulator of exact and approximate coalescent with selection
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DOI：
10.1093/bioinformatics/btu562
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发表时间：
2014-12-01
期刊：
影响因子：
5.8
通讯作者：
Schaffner, Stephen F.
中科院分区：
文献类型：
--
作者：
Shlyakhter, Ilya;Sabeti, Pardis C.;Schaffner, Stephen F.
动机：在给定的人口模型下有效地模拟人口遗传样本是进行许多分析的先决条件。聚结理论为这类模拟提供了一个有效的框架，但模拟更长的区域和更高的重组率仍然具有挑战性。基于马尔可夫近似的模拟器很好地结合了规模，但不支持模拟选择。结果：我们描述了Cosi2，一个支持正选择的精确和近似合并模拟的高效模拟器。Cosi2提高了现有精确模拟器的速度，并允许在近似模式下进一步加速，同时保留对选择的支持。Cosi2支持广泛的人口情景，包括重组热点、基因转换、人口规模变化、人口结构和迁移。Cosi2通过仅跟踪祖先重组图的一小部分、仅对相关重组事件进行采样以及使用扩展跳过列表来表示被跟踪的基因片段，从而有效地实现了合并机制。为了保持对近似模式选择的支持，马尔可夫近似不是通过沿染色体移动来实现的，而是通过执行标准的向后时间合并模拟来实现的，同时将合并限制在具有重叠或接近重叠的遗传物质的节点对上。我们描述了Cosi2使用的算法，并与现有的选择模拟器进行了比较。
Motivation: Efficient simulation of population genetic samples under a given demographic model is a prerequisite for many analyses. Coalescent theory provides an efficient framework for such simulations, but simulating longer regions and higher recombination rates remains challenging. Simulators based on a Markovian approximation to the coalescent scale well, but do not support simulation of selection. Gene conversion is not supported by any published coalescent simulators that support selection.Results: We describe cosi2, an efficient simulator that supports both exact and approximate coalescent simulation with positive selection. cosi2 improves on the speed of existing exact simulators, and permits further speedup in approximate mode while retaining support for selection. cosi2 supports a wide range of demographic scenarios, including recombination hot spots, gene conversion, population size changes, population structure and migration. cosi2 implements coalescent machinery efficiently by tracking only a small subset of the Ancestral Recombination Graph, sampling only relevant recombination events, and using augmented skip lists to represent tracked genetic segments. To preserve support for selection in approximate mode, the Markov approximation is implemented not by moving along the chromosome but by performing a standard backwards- in-time coalescent simulation while restricting coalescence to node pairs with overlapping or near-overlapping genetic material. We describe the algorithms used by cosi2 and present comparisons with existing selection simulators.