Bioinformatics Advance Access published online on January 28, 2008
Bioinformatics, doi:10.1093/bioinformatics/btn032
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Compressed Indexing and Local Alignment of DNA
1Department of Computer Science, University of Hong Kong, Hong Kong.
2Department of Computer Science, National University of Singapore, Singapore.
To whom correspondence should be addressed. Dr. Tak-Wah Lam, E-mail: twlam{at}cs.hku.hk
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Abstract |
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Motivation: Recent experimental studies on compressed indexes (BWT, CSA, FM-index) have confirmed their practicality for indexing very long strings such as the human genome in the main memory [7, 13, 18]. For example, a BWT index for the human genome (with about 3 billion characters) occupies just around 1G bytes. However, these indexes are designed for exact pattern matching, which is too stringent for biological applications. The demand is often on finding local alignments (pairs of similar substrings with gaps allowed). Without indexing, one can use dynamic programming to find all the local alignments between a text T and a pattern P in O(||T||P||) time [23], but this would be too slow when the text is of genome scale (e.g., aligning a gene with the human genome would take tens to hundreds of hours). In practice, biologists use heuristic-based software such as BLAST, which is very efficient but doesn't guarantee to find all local alignments.
Results: In this paper, we show how to build a software called BWTSW that exploits a BWT index of a text T to speed up the dynamic programming for finding all local alignments. Experiments reveal that BWT-SW is very efficient (e.g., aligning a pattern of length 3,000 with the human genome takes less than a minute). We have also analyzed BWT-SW mathematically for a simpler similarity model (with gaps disallowed), and we show that the expected running time is O(||T||0.628||P||) for random strings. As far as we know, BWT-SWis the first practical tool that can find all local alignments. Yet BWT-SWis not meant to be a replacement of BLAST, as BLAST is still several times faster than BWT-SW for long patterns and BLAST is indeed accurate enough in most cases (we have used BWT-SW to check against the accuracy of BLAST and found that only rarely BLAST would miss some significant alignments).
Availability: www.cs.hku.hk/~ckwong3/bwtsw.
Associate Editor: Prof. Thomas Lengauer
Received on August 29, 2007; revised on December 8, 2007; accepted on January 22, 2008
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