An Algorithm to Build a Multi-genome Reference

1MotivationNew DNA sequencing technologies have enabled the rapid analysis of many thousands of genomes from a single species. At the same time, the conventional approach of mapping sequencing reads against a single reference genome sequence is no longer adequate. However, even where multiple high-quality reference genomes are available, the problem remains how one would integrate results from pairwise analyses. ResultTo overcome the limits imposed by mapping sequence reads against a single reference genome, or serially mapping them against multiple reference genomes, we have developed the MGR method that allows simultaneous comparison against multiple high-quality reference genomes, in order to remove the bias that comes from using only a single-genome reference and to simplify downstream analyses. To this end, we present the MGR algorithm that creates a graph (MGR graph) as a multi-genome reference. To reduce the size and complexity of the multi-genome reference, highly similar orthologous1 and paralogous2 regions are collapsed while more substantial differences are retained. To evaluate the performance of our model, we have developed a genome compression tool, which can be used to estimate the amount of shared information between genomes. Availabilityhttps://github.com/LeilyR/Multi-genome-Reference.git Contactweigel@tue.mpg.de