Multiple sequence alignment with user-defined constraints

Abstract

In many situations, automated multi-alignment programs are not able to correctly align families of nucleic acid or protein sequences. Distantly related sequences are generally hard to align, and sequence duplications may present additional challenges to standard alignment algorithms. In the present paper, we describe a semiautomatic approach to multiple sequence alignment. The user can specify parts of the sequences that are thought to be related to each other; our software program will use these sites as anchor points and create a multiple alignment respecting these userdefined constraints. By using functionally, structurally or evolutionarily related positions of the input sequences as anchor points, the proposed method can produce alignments that are biologically more meaningful than alignments produced by fully automated procedures. We apply our approach to genomic sequences around the Hox gene cluster. As a by-product, we obtain useful insights for the further development of alignment algorithms. The described alignment approach has been integrated into the tracker software system.