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Bioinformatics Vol. 19 no. 8 2003
Pages 999-1008
© 2003 Oxford University Press

Generating consensus sequences from partial order multiple sequence alignment graphs

Christopher Lee 1,2

1 UCLA-DOE Center for Genomics and Proteomics, Molecular Biology Institute
2 Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095-1570, USA

Received on October 3, 2002 ; revised on December 10, 2002 ; accepted on December 20, 2002

Motivation: Consensus sequence generation is important in many kinds of sequence analysis ranging from sequence assembly to profile-based iterative search methods. However, how can a consensus be constructed when its inherent assumption—that the aligned sequences form a single linear consensus—is not true?

Results: Partial Order Alignment (POA) enables construction and analysis of multiple sequence alignments as directed acyclic graphs containing complex branching structure. Here we present a dynamic programming algorithm (heaviest_bundle) for generating multiple consensus sequences from such complex alignments. The number and relationships of these consensus sequences reveals the degree of structural complexity of the source alignment. This is a powerful and general approach for analyzing and visualizing complex alignment structures, and can be applied to any alignment. We illustrate its value for analyzing expressed sequence alignments to detect alternative splicing, reconstruct full length mRNA isoform sequences from EST fragments, and separate paralog mixtures that can cause incorrect SNP predictions.

Availability: The heaviest_bundle source code is available at http://www.bioinformatics.ucla.edu/poa

Contact: leec{at}mbi.ucla.edu

* To whom correspondence should be addressed.


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