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Inference of Ancestral Recombination Graphs through Topological Data Analysis

机译:通过拓扑数据分析推断祖先重组图

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摘要

The recent explosion of genomic data has underscored the need for interpretable and comprehensive analyses that can capture complex phylogenetic relationships within and across species. Recombination, reassortment and horizontal gene transfer constitute examples of pervasive biological phenomena that cannot be captured by tree-like representations. Starting from hundreds of genomes, we are interested in the reconstruction of potential evolutionary histories leading to the observed data. Ancestral recombination graphs represent potential histories that explicitly accommodate recombination and mutation events across orthologous genomes. However, they are computationally costly to reconstruct, usually being infeasible for more than few tens of genomes. Recently, Topological Data Analysis (TDA) methods have been proposed as robust and scalable methods that can capture the genetic scale and frequency of recombination. We build upon previous TDA developments for detecting and quantifying recombination, and present a novel framework that can be applied to hundreds of genomes and can be interpreted in terms of minimal histories of mutation and recombination events, quantifying the scales and identifying the genomic locations of recombinations. We implement this framework in a software package, called TARGet, and apply it to several examples, including small migration between different populations, human recombination, and horizontal evolution in finches inhabiting the Galápagos Islands.
机译:最近基因组数据的爆炸式增长强调了对可解释和全面分析的需求,这些分析可以捕获物种内部和物种之间的复杂系统发育关系。重组,重组和水平基因转移构成了无法被树状表征捕获的普遍生物现象的例子。从数百个基因组开始,我们对导致观察数据的潜在进化历史的重建感兴趣。祖先的重组图代表了潜在的历史,这些历史明确地适应了直系同源基因组中的重组和突变事件。然而,它们的重建在计算上是昂贵的,通常对于数十个基因组来说是不可行的。最近,拓扑数据分析(TDA)方法已被提出为可捕获遗传规模和重组频率的稳健且可扩展的方法。我们以先前的TDA开发为基础,用于检测和定量重组,并提出了一种新颖的框架,该框架可应用于数百个基因组,并且可以解释为突变和重组事件的最小历史记录,量化规模并确定重组的基因组位置。我们在称为TARGet的软件包中实现了该框架,并将其应用于几个示例,包括不同人群之间的小规模迁徙,人类重组以及加拉帕戈斯群岛上栖息的雀科动物的水平进化。

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