Comparing DNA sequence collections by direct comparison of compressed text indexes

TL;DR

This paper introduces a method to compare large DNA sequence collections directly using their BWT indexes stored on disk, enabling reference-free analysis such as predicting splice junctions.

Contribution

It demonstrates that BWTs of large sequence collections can be compared efficiently without loading into RAM, facilitating new reference-free genomic analyses.

Findings

BWT comparison can be performed entirely from external memory

The method enables reference-free prediction of splice junctions

Code for BWT construction and comparison is publicly available

Abstract

Popular sequence alignment tools such as BWA convert a reference genome to an indexing data structure based on the Burrows-Wheeler Transform (BWT), from which matches to individual query sequences can be rapidly determined. However the utility of also indexing the query sequences themselves remains relatively unexplored. Here we show that an all-against-all comparison of two sequence collections can be computed from the BWT of each collection with the BWTs held entirely in external memory, i.e. on disk and not in RAM. As an application of this technique, we show that BWTs of transcriptomic and genomic reads can be compared to obtain reference-free predictions of splice junctions that have high overlap with results from more standard reference-based methods. Code to construct and compare the BWT of large genomic data sets is available at http://beetl.github.com/BEETL/ as part of the BEETL library.