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Nucleic Acids Research 2006 34(6):1692-1699; doi:10.1093/nar/gkl091
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Published online 23 March 2006

© The Author 2006. Published by Oxford University Press. All rights reserved
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org


Computational Method and +G1 Genomics

M-Coffee: combining multiple sequence alignment methods with T-Coffee

Iain M. Wallace, Orla O'Sullivan, Desmond G. Higgins and Cedric Notredame1,*

The Conway Institute of Biomolecular and Biomedical Research, University College Dublin Ireland 1Laboratoire Information Génomique et Structurale, CNRS UPR2589, Institute for Structural Biology and Microbiology (IBSM) Parc Scientifique de Luminy, 163 Avenue de Luminy, 13288, Marseille cedex 09, France

*To whom correspondence should be addressed. Tel: +33 491 825 427; Fax: +33 491 825 420; Email: cedric.notredame{at}europe.com

Received January 19, 2006. Revised February 7, 2006. Accepted March 7, 2006.

We introduce M-Coffee, a meta-method for assembling multiple sequence alignments (MSA) by combining the output of several individual methods into one single MSA. M-Coffee is an extension of T-Coffee and uses consistency to estimate a consensus alignment. We show that the procedure is robust to variations in the choice of constituent methods and reasonably tolerant to duplicate MSAs. We also show that performances can be improved by carefully selecting the constituent methods. M-Coffee outperforms all the individual methods on three major reference datasets: HOMSTRAD, Prefab and Balibase. We also show that on a case-by-case basis, M-Coffee is twice as likely to deliver the best alignment than any individual method. Given a collection of pre-computed MSAs, M-Coffee has similar CPU requirements to the original T-Coffee. M-Coffee is a freeware open-source package available from http://www.tcoffee.org/.


The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors


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