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

Grytten, I.; Rand, K. D.; Nederbragt, A. J.; Sandve, G. K.

doi:10.1101/538066

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bioRxiv · 10.1101/538066

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

Grytten, I.·Rand, K. D.·Nederbragt, A. J.·Sandve, G. K.

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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 two 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.

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Grytten, I., Rand, K. D., Nederbragt, A. J., Sandve, G. K.. 2019-02-01. Assessing graph-based read mappers against a novel baseline approach highlights strengths and weaknesses of the current generation of methods. https://doi.org/10.1101/538066

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