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Assessing graph-based read mappers against a novel baseline approach highlights strengths and weaknesses of the current generation of methods

View ORCID ProfileIvar Grytten, View ORCID ProfileKnut D. Rand, View ORCID ProfileAlexander J. Nederbragt, View ORCID ProfileGeir K. Sandve
doi: https://doi.org/10.1101/538066
Ivar Grytten
1Department of informatics, University of Oslo, Oslo, Norway
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Knut D. Rand
2Department of Mathematics, University of Oslo, Oslo, Norway
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Alexander J. Nederbragt
1Department of informatics, University of Oslo, Oslo, Norway
3Department of Biosciences, University of Oslo, Oslo, Norway
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Geir K. Sandve
1Department of informatics, University of Oslo, Oslo, Norway
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Abstract

Graph-based reference genomes have become popular as they allow read mapping and follow-up analyses in settings where the exact haplotypes underlying a high-throughput sequencing experiment are not precisely known. Two recent papers show that mapping to graph-based reference genomes can improve accuracy as compared to methods using linear references. Both of these methods index the sequences for most paths up to a certain length in the graph in order to enable direct mapping of reads containing common variants. However, the combinatorial explosion of possible paths through nearby variants also leads to a huge search space and an increased chance of false positive alignments to highly variable regions.

We here assess three prominent graph-based read mappers against a novel hybrid baseline approach that combines an initial path determination with a tuned linear read mapping method. We show, using a previously proposed benchmark, that this simple approach is able to improve accuracy of read-mapping to graph-based reference genomes.

Our method is implemented in a tool Two-step Graph Mapper, which is available at https://github.com/uio-bmi/two_step_graph_mapper along with data and scripts for reproducing the experiments.

Footnotes

  • ↵* ivargry{at}ifi.uio.no

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted March 12, 2019.
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Assessing graph-based read mappers against a novel baseline approach highlights strengths and weaknesses of the current generation of methods
Ivar Grytten, Knut D. Rand, Alexander J. Nederbragt, Geir K. Sandve
bioRxiv 538066; doi: https://doi.org/10.1101/538066
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Assessing graph-based read mappers against a novel baseline approach highlights strengths and weaknesses of the current generation of methods
Ivar Grytten, Knut D. Rand, Alexander J. Nederbragt, Geir K. Sandve
bioRxiv 538066; doi: https://doi.org/10.1101/538066

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