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Sequence variation aware genome references and read mapping with the variation graph toolkit
Adam M Novak,
Jordan M Eizenga,
Eric T. Dawson,
Michael F Lin,
Posted 15 Dec 2017
bioRxiv DOI: 10.1101/234856 (published DOI: 10.1038/nbt.4227)
Posted 15 Dec 2017
Reference genomes guide our interpretation of DNA sequence data. However, conventional linear references are fundamentally limited in that they represent only one version of each locus, whereas the population may contain multiple variants. When the reference represents an individual's genome poorly, it can impact read mapping and introduce bias. Variation graphs are bidirected DNA sequence graphs that compactly represent genetic variation, including large scale structural variation such as inversions and duplications. Equivalent structures are produced by de novo genome assemblers. Here we present vg, a toolkit of computational methods for creating, manipulating, and utilizing these structures as references at the scale of the human genome. vg provides an efficient approach to mapping reads onto arbitrary variation graphs using generalized compressed suffix arrays, with improved accuracy over alignment to a linear reference, creating data structures to support downstream variant calling and genotyping. These capabilities make using variation graphs as reference structures for DNA sequencing practical at the scale of vertebrate genomes, or at the topological complexity of new species assemblies.
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