RT Journal
A1 Varki, Rahul
A1 Rossi, Massimiliano
A1 Ferro, Eddie
A1 Oliva, Marco
A1 Garrison, Erik
A1 Langmead, Ben
A1 Boucher, Christina
T1 Accurate short-read alignment through r-index-based pangenome indexing
JF Genome Research 
JO Genome Research 
YR 2025 
FD July 01 
VO 35 
IS 7 
SP 1609 
OP 1620 
DO 10.1101/gr.279858.124 
UL http://genome.cshlp.org/content/35/7/1609.abstract 
AB Aligning to a linear reference genome can result in a higher percentage of reads going unmapped or being incorrectly mapped owing to variations not captured by the reference, otherwise known as reference bias. Recently, in efforts to mitigate reference bias, there has been a movement to switch to using pangenomes, a collection of genomes, as the reference. In this paper, we introduce Moni-align, the first short-read pangenome aligner built on the r-index, a variation of the classical FM-index that can index collections of genomes in O(r)-space, where r is the number of runs in the Burrows–Wheeler transform. Moni-align uses a seed-and-extend strategy for aligning reads, utilizing maximal exact matches as seeds, which can be efficiently obtained with the r-index. Using both simulated and real short-read data sets, we demonstrate that Moni-align achieves alignment accuracy comparable to vg map and vg giraffe, the leading pangenome aligners. Although currently best suited for aligning to localized pangenomes owing to computational constraints, Moni-align offers a robust foundation for future optimizations that could further broaden its applicability.