The TAG array of a multiple sequence alignment

TL;DR

The paper tackles efficient pangenome indexing by combining a run-length encoded TAG array with the $BWT$-based index to map matches to specific MSA columns. It develops a space-efficient construction, a sampled TAG index with document-listing to report distinct TAG values within a $BWT$ interval in time proportional to the output, and a strategy to project MEM matches to a designated reference. The authors demonstrate that TAG enables fast, reference-projected mapping of seeds for seed-and-extend pipelines while reducing memory usage, demonstrated on real human haplotype data. This approach provides a practical bridge between linear reference projection and pangenome indexing, enabling applications like improved seed chaining in ropebwt3 and related tools.

Abstract

Modern genomic analyses increasingly rely on pangenomes, that is, representations of the genome of entire populations. The simplest representation of a pangenome is a set of individual genome sequences. Compared to e.g. sequence graphs, this has the advantage that efficient exact search via indexes based on the Burrows-Wheeler Transform (BWT) is possible, that no chimeric sequences are created, and that the results are not influenced by heuristics. However, such an index may report a match in thousands of positions even if these all correspond to the same locus, making downstream analysis unnecessarily expensive. For sufficiently similar sequences (e.g. human chromosomes), a multiple sequence alignment (MSA) can be computed. Since an MSA tends to group similar strings in the same columns, it is likely that a string occurring thousands of times in the pangenome can be described by very few columns in the MSA. We describe a method to tag entries in the BWT with the corresponding column in the MSA and develop an index that can map matches in the BWT to columns in the MSA in time proportional to the output. As a by-product, we can efficiently project a match to a designated reference genome, a capability that current pangenome aligners based on the BWT lack.