A Lagrangian relaxation approach for the multiple sequence alignment problem

We present a branch-and-bound (bb) algorithm for the multiple sequence alignment problem (MSA), one of the most important problems in computational biology. The upper bound at each bb node is based on a Lagrangian relaxation of an integer linear programming formulation for MSA. Dualizing certain inequalities, the Lagrangian subproblem becomes a pairwise alignment problem, which can be solved efficiently by a dynamic programming approach. Due to a reformulation w.r.t. additionally introduced variables prior to relaxation we improve the convergence rate dramatically while at the same time being able to solve the Lagrangian problem efficiently. Our experiments show that our implementation, although preliminary, outperforms all exact algorithms for the multiple sequence alignment problem

An exact mathematical programming approach to multiple RNA sequence-structure alignment

One of the main tasks in computational biology is the computation of alignments of genomic sequences to reveal their commonalities. In case of DNA or protein sequences, sequence information alone is usually sufficient to compute reliable alignments. RNA molecules, however, build spatial conformations—the secondary structure—that are more conserved than the actual sequence. Hence, computing reliable alignments of RNA molecules has to take into account the secondary structure. We present a novel framework for the computation of exact multiple sequence-structure alignments: We give a graph- theoretic representation of the sequence-structure alignment problem and phrase it as an integer linear program. We identify a class of constraints that make the problem easier to solve and relax the original integer linear program in a Lagrangian manner. Experiments on a recently published benchmark show that our algorithms has a comparable performance than more costly dynamic programming algorithms, and outperforms all other approaches in terms of solution quality with an increasing number of input sequences

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

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. Conclusions: 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 inpu