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Nucleic Acids Research 2005 33(8):2433-2439; doi:10.1093/nar/gki541
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Published online 28 April 2005

© The Author 2005. Published by Oxford University Press. All rights reserved
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Article

A benchmark of multiple sequence alignment programs upon structural RNAs

Paul P. Gardner*, Andreas Wilm1 and Stefan Washietl2

Department of Evolutionary Biology, University of Copenhagen Universitetsparken 15, 2100 Copenhagen Ø, Denmark 1Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf Universitätsstrasse 1, D-40225 Düsseldorf, Germany 2Institut für Theoretische Chemie, Universität Wien Währingerstrasse 17, A-1090 Wien, Austria

*To whom correspondence should be addressed. Tel: +45 3532 1338; Fax: +45 3532 1300; Email: PPGardner{at}bi.ku.dk

Received March 1, 2005. Revised April 12, 2005. Accepted April 12, 2005.

To date, few attempts have been made to benchmark the alignment algorithms upon nucleic acid sequences. Frequently, sophisticated PAM or BLOSUM like models are used to align proteins, yet equivalents are not considered for nucleic acids; instead, rather ad hoc models are generally favoured. Here, we systematically test the performance of existing alignment algorithms on structural RNAs. This work was aimed at achieving the following goals: (i) to determine conditions where it is appropriate to apply common sequence alignment methods to the structural RNA alignment problem. This indicates where and when researchers should consider augmenting the alignment process with auxiliary information, such as secondary structure and (ii) to determine which sequence alignment algorithms perform well under the broadest range of conditions. We find that sequence alignment alone, using the current algorithms, is generally inappropriate <50–60% sequence identity. Second, we note that the probabilistic method ProAlign and the aging Clustal algorithms generally outperform other sequence-based algorithms, under the broadest range of applications.


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