Fast and accurate long-read alignment with Burrows-Wheeler transform

Abstract

Motivation: Many programs for aligning short sequencing reads to a reference genome have been developed in the last 2 years. Most of them are very efficient for short reads but inefficient or not applicable for reads >200 bp because the algorithms are heavily and specifically tuned for short queries with low sequencing error rate. However, some sequencing platforms already produce longer reads and others are expected to become available soon. For longer reads, hashing-based software such as BLAT and SSAHA2 remain the only choices. Nonetheless, these methods are substantially slower than short-read aligners in terms of aligned bases per unit time.

Results: We designed and implemented a new algorithm, Burrows-Wheeler Aligner's Smith-Waterman Alignment (BWA-SW), to align long sequences up to 1 Mb against a large sequence database (e.g. the human genome) with a few gigabytes of memory. The algorithm is as accurate as SSAHA2, more accurate than BLAT, and is several to tens of times faster than both.

Availability: http://bio-bwa.sourceforge.net

Fig. 1.

Prefix trie and prefix DAWG of string ‘GOOGOL’. (A) Prefix trie. Symbol ‘∧’ marks the start of a string. The two numbers in a node gives the SA interval of the node. (B) Prefix DAWG constructed by collapsing nodes with the identical SA interval. For example, in the prefix trie, three nodes has SA interval [4, 4]. Their parents have interval [1, 2], [1, 2] and [1, 1], respectively. In the prefix DAWG, the [4, 4] node thus has parents [1, 2] and [1, 1]. Node [4, 4] represents three strings ‘OG’, ‘OGO’ and ‘OGOL’ with the first two strings being the prefix of ‘OGOL’. (A) is modified from Figure 1 in Li and Durbin (2009).