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Bioinformatics Advance Access originally published online on November 13, 2005
Bioinformatics 2006 22(1):29-34; doi:10.1093/bioinformatics/bti772
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Published by Oxford University Press 2005

Accurate anchoring alignment of divergent sequences

Weichun Huang 1,2,3, David M. Umbach 1 and Leping Li 1,*

1Biostatistics Branch, The National Institute of Environmental Health Sciences RTP, NC 27709 USA
2Bioinformatics Research Center, North Carolina State University Raleigh, NC 27606 USA
3Institute for Genome Sciences & Policy, Duke University Medical Center Durham, NC 27708 USA

*To whom correspondence should be addressed.

Motivation: Obtaining high quality alignments of divergent homologous sequences for cross-species sequence comparison remains a challenge.

Results: We propose a novel pairwise sequence alignment algorithm, ACANA (ACcurate ANchoring Alignment), for aligning biological sequences at both local and global levels. Like many fast heuristic methods, ACANA uses an anchoring strategy. However, unlike others, ACANA uses a Smith–Waterman-like dynamic programming algorithm to recursively identify near-optimal regions as anchors for a global alignment. Performance evaluations using a simulated benchmark dataset and real promoter sequences suggest that ACANA is accurate and consistent, especially for divergent sequences. Specifically, we use a simulated benchmark dataset to show that ACANA has the highest sensitivity to align constrained functional sites compared to BLASTZ, CHAOS and DIALIGN for local alignment and compared to AVID, ClustalW, DIALIGN and LAGAN for global alignment. Applied to 6007 pairs of human-mouse orthologous promoter sequences, ACANA identified the largest number of conserved regions (defined as over 70% identity over 100 bp) compared to AVID, ClustalW, DIALIGN and LAGAN. In addition, the average length of conserved region identified by ACANA was the longest. Thus, we suggest that ACANA is a useful tool for identifying functional elements in cross-species sequence analysis, such as predicting transcription factor binding sites in non-coding DNA.

Availability: ACANA software and test sequence data are publicly available at http://BioMedEmpire.org/

Supplementary information: Supplementary materials are available at Bioinformatics online.

Contact: li3{at}niehs.nih.gov

Received on July 1, 2005; revised on October 14, 2005; accepted on November 8, 2005

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