Improving the time and space complexity of the WFA algorithm and generalizing its scoring

MotivationModern genomic sequencing data is trending toward longer sequences with higher accuracy. Many analyses using these data will center on alignments, but classical exact alignment algorithms are infeasible for long sequences. The recently proposed WFA algorithm demonstrated how to perform exact alignment for long, similar sequences in O(sN) time and O(s2) memory, where s is a score that is low for similar sequences (Marco-Sola et al., 2021). However, this algorithm still has infeasible memory requirements for longer sequences. Also, it uses an alternate scoring system that is unfamiliar to many bioinformaticians. ResultsWe describe variants of WFA that improve its asymptotic memory use from O(s2) to O(s3/2) and its asymptotic run time from O(sN) to O(s2 + N). We expect the reduction in memory use to be particularly impactful, as it makes it practical to perform highly multithreaded megabase-scale exact alignments in common compute environments. In addition, we show how to fold WFAs alternate scoring into the broader literature on alignment scores. AvailabilityAll code is publicly available for use and modification at https://github.com/jeizenga/wfalm. Contactjeizenga@ucsc.edu Supplementary informationSupplementary data are available online.