Establish correct whole-genome alignments for interpreting pangenome graph topology

Establish the correct nucleotide-level alignment between two whole genomes and, more generally, among multiple genomes, to enable biologically meaningful interpretation of pangenome graph topology generated from multiple sequence alignment procedures with complex parameterization.

Background

The paper highlights that pangenome graphs are derived from multiple sequence alignments produced by complex pipelines with many parameters, making it difficult to assess whether the resulting graph structures are biologically meaningful.

The authors explicitly note that the correct alignment between two genomes—and by extension, among multiple genomes—is unknown, which limits confidence in graph-based analyses and motivates exact, BWT-based alternatives despite their more restricted query types.