HAT: Haplotype Assembly Tool using short and error-prone long reads

Abstract

MotivationHaplotypes are the set of alleles cooccurring on a single chromosome and inherited together to the next generation. Because a monoploid reference genome loses this co-occurrence information, its usability is limited to associate phenotypes with allelic combinations of genotypes. Therefore, methods to reconstruct the complete haplotypes from DNA sequencing data are crucial. Recently, several attempts have been made at haplotype reconstructions, but significant limitations remain. High-quality continuous haplotypes cannot be created reliably, particularly when there are few differences between the homologous chromosomes. ResultsHere, we introduce HAT, a haplotype assembly tool that exploits short and long reads along with a reference genome to reconstruct haplotypes. HAT tries to take advantage of the accuracy of short reads and the length of the long reads to reconstruct haplotypes. We tested HAT on the aneuploid yeast strain Saccharomyces pastorianus CBS1483 and multiple simulated polyploid data sets of the same strain, showing that it outperforms existing tools. Availabilityhttps://github.com/AbeelLab/hat/ Contactt.abeel@tudelft.nl