PT  - JOURNAL ARTICLE
AU  - Ivar Grytten
AU  - Knut D. Rand
AU  - Alexander J. Nederbragt
AU  - Geir K. Sandve
TI  - Assessing graph-based read mappers against a novel baseline approach highlights strengths and weaknesses of the current generation of methods
AID  - 10.1101/538066
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 538066
4099  - http://biorxiv.org/content/early/2019/03/12/538066.short
4100  - http://biorxiv.org/content/early/2019/03/12/538066.full
AB  - 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.