Chuong B. Do, Michael Brudno, and Serafim Batzoglou
Obtaining an accurate multiple alignment of protein sequences is a difficult computational problem for which many heuristic techniques sacrifice optimality to achieve reasonable running times. The most commonly used heuristic is progressive alignment, which merges sequences into a multiple alignment by pairwise comparisons along the nodes of a guide tree. To improve accuracy, consistency-based methods take advantage of conservation across many sequences to provide a stronger signal for pairwise comparisons. In this paper, we introduce the concept of probabilistic consistency for multiple sequence alignments. We also present PROBCONS, an HMM-based protein multiple sequence aligner, based on an approximation of the probabilistic consistency objective function. On the BAliBASE benchmark alignment database, PROBCONS demonstrates a statistically significant improvement in accuracy compared to several leading alignment programs while maintaining practical running times.