The TAG array of a multiple sequence alignment

TL;DR

This paper introduces a method to integrate multiple sequence alignments with BWT-based pangenome indexes, enabling efficient mapping of matches to MSA columns and projecting matches to a reference genome, improving analysis efficiency.

Contribution

It presents a novel indexing approach that tags BWT entries with MSA columns, facilitating faster mapping and reference projection in pangenome analysis.

Findings

Efficient mapping of BWT matches to MSA columns.

Capability to project matches to a reference genome.

Improved downstream analysis efficiency.

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.