🍩 Database of Original & Non-Theoretical Uses of Topology
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Inference of Ancestral Recombination Graphs Through Topological Data Analysis (2016)Pablo G. Cámara, Arnold J. Levine, Raúl Rabadán
AbstractThe 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., Evolution occurs through different mechanisms, including point mutations, gene duplication, horizontal gene transfer, and recombinations. Some of these mechanisms cannot be captured by tree graphs. We present a framework, based on the mathematical tools of computational topology, that can explicitly accommodate both recombination and mutation events across the evolutionary history of a sample of genomic sequences. This approach generates a new type of summary graph and algebraic structures that provide quantitative information on the evolutionary scale and frequency of recombination events. The accompanying software, TARGet, is applied to several examples, including migration between sexually-reproducing populations, human recombination, and recombination in Darwin’s finches.