AbstractAs genome sequencing tools and techniques improve, researchers are able to incrementally assemble more accurate reference genomes, which enable sensitivity in read mapping and downstream analysis such as variant calling. A more sensitive downstream analysis is critical for a better understanding of the genome donor (e.g., health characteristics). Therefore, read sets from sequenced samples should ideally be mapped to the latest available reference genome that represents the most relevant population. Unfortunately, the increasingly large amount of available genomic data makes it prohibitively expensive to fully re-map each read set to its respective reference genome every time the reference is updated. There are several tools that attempt to accelerate the process of updating a read data set from one reference to another (i.e., remapping) by 1) identifying regions that appear similarly between two references and 2) updating the mapping location of reads that map to any of the identified regions in the old reference to the corresponding similar region in the new reference. The main drawback of existing approaches is that if a read maps to a region in the old reference that does not appear with a reasonable degree of similarity in the new reference, the read cannot be remapped. We find that, as a result of this drawback, a significant portion of annotations (i.e., coding regions in a genome) are lost when using state-of-the-art remapping tools. To address this major limitation in existing tools, we propose AirLift, a fast and comprehensive technique for remapping alignments from one genome to another. Compared to the state-of-the-art method for remapping reads (i.e., full mapping), AirLift reduces 1) the number of reads (out of the entire read set) that need to be fully mapped to the new reference by up to 99.99% and 2) the overall execution time to remap read sets between two reference genome versions by 6.7×, 6.6×, and 2.8× for large (human), medium (C. elegans), and small (yeast) reference genomes, respectively. We validate our remapping results with GATK and find that AirLift provides similar accuracy in identifying ground truth SNP and INDEL variants as the baseline of fully mapping a read set.Code AvailabilityAirLift source code and readme describing how to reproduce our results are available at https://github.com/CMU-SAFARI/AirLift.
Scaffolding Contigs Using Multiple Reference Genomes