Efficient methods for multiple sequence alignment with guaranteed error bounds

Abstract

Multiple string (sequence) alignment is a difficult and important problem in computational biology, where it is central in two related tasks: finding highly conserved subregions or embedded patterns of a set of biological sequences (strings of DNA, RNA or amino acids), and inferring the evolutionary history of a set of taxa from their associated biological sequences. Several precise measures have been proposed for evaluating the goodness of a multiple alignment, but no efficient methods are known which compute the optimal alignment for any of these measures in any but small cases. In this paper, we consider two previously proposed measures, and give two computationaly efficient multiple alignment methods (one for each measure) whose deviation from the optimal value is guaranteed to be less than a factor of two. This is the novel feature of thse methods. but the methods have additional virtues as well. For both methods, the guaranteed bounds are much smaller than two when the number of strings is small (1.33 for three strings of any length); for one of the methods we give a related randomized method which is much faster and which gives, with high probability, multiple alignments with fairly small error bounds; and for the other measure, the method given yields a non-obvious lower bound on the optimal alignment.