The M-Coffee web server: a meta-method for computing multiple sequence alignments by combining alternative alignment methods

Abstract

The M-Coffee server is a web server that makes it possible to compute multiple sequence alignments (MSAs) by running several MSA methods and combining their output into one single model. This allows the user to simultaneously run all his methods of choice without having to arbitrarily choose one of them. The MSA is delivered along with a local estimation of its consistency with the individual MSAs it was derived from. The computation of the consensus multiple alignment is carried out using a special mode of the T-Coffee package [Notredame, Higgins and Heringa (T-Coffee: a novel method for fast and accurate multiple sequence alignment. J. Mol. Biol. 2000; 302: 205-217); Wallace, O'Sullivan, Higgins and Notredame (M-Coffee: combining multiple sequence alignment methods with T-Coffee. Nucleic Acids Res. 2006; 34: 1692-1699)] Given a set of sequences (DNA or proteins) in FASTA format, M-Coffee delivers a multiple alignment in the most common formats. M-Coffee is a freeware open source package distributed under a GPL license and it is available either as a standalone package or as a web service from www.tcoffee.org.

Figure 1.

Method selection on the advanced M-Coffee server form. Each check box corresponds to either a pairwise (_pair) or a multiple sequence alignment method (_msa). Users should choose their methods of choice in order to combine them.

Figure 2.

Typical colored output. This output was obtained by using the kinase1_ref5 from BaliBase. Correctly aligned residues (as judged from the reference) are in upper case, non-correct ones are in lower case. In this colored output, each residue has a color that indicates the agreement of the individual MSAs with respect to the alignment of that specific residue. Dark red indicates residues aligned in a similar fashion among all the individual MSAs; blue indicates a very low agreement. Dark yellow, orange and red residues can be considered to be reliably aligned.