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Open Access Highly Accessed Methodology article

Accurate multiple sequence-structure alignment of RNA sequences using combinatorial optimization

Markus Bauer12*, Gunnar W Klau13* and Knut Reinert1

Author Affiliations

1 Department of Mathematics and Computer Science, Free University Berlin, 14195 Berlin, Germany

2 International Max Planck Research School for Computational Biology and Scientific Computing, Berlin, Germany

3 DFG Research Center Matheon, Berlin, Germany

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BMC Bioinformatics 2007, 8:271  doi:10.1186/1471-2105-8-271

Published: 27 July 2007

Abstract

Background

The discovery of functional non-coding RNA sequences has led to an increasing interest in algorithms related to RNA analysis. Traditional sequence alignment algorithms, however, fail at computing reliable alignments of low-homology RNA sequences. The spatial conformation of RNA sequences largely determines their function, and therefore RNA alignment algorithms have to take structural information into account.

Results

We present a graph-based representation for sequence-structure alignments, which we model as an integer linear program (ILP). We sketch how we compute an optimal or near-optimal solution to the ILP using methods from combinatorial optimization, and present results on a recently published benchmark set for RNA alignments.

Conclusion

The implementation of our algorithm yields better alignments in terms of two published scores than the other programs that we tested: This is especially the case with an increasing number of input sequences. Our program LARA is freely available for academic purposes from http://www.planet-lisa.net webcite.