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Nucleic Acids Res. 2010 Oct;38(19):6338-49. doi: 10.1093/nar/gkq526. Epub 2010 Jun 8.

AlexSys: a knowledge-based expert system for multiple sequence alignment construction and analysis.

Author information

1
Department of Structural Biology and Genomics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, Institut National de la Santé et de la Recherche Médicale, The Centre National de la Recherche Scientifique, UMR7104, F-67400 Illkirch, Université Louis Pasteur, F-67000 Strasbourg, France.

Abstract

Multiple sequence alignment (MSA) is a cornerstone of modern molecular biology and represents a unique means of investigating the patterns of conservation and diversity in complex biological systems. Many different algorithms have been developed to construct MSAs, but previous studies have shown that no single aligner consistently outperforms the rest. This has led to the development of a number of 'meta-methods' that systematically run several aligners and merge the output into one single solution. Although these methods generally produce more accurate alignments, they are inefficient because all the aligners need to be run first and the choice of the best solution is made a posteriori. Here, we describe the development of a new expert system, AlexSys, for the multiple alignment of protein sequences. AlexSys incorporates an intelligent inference engine to automatically select an appropriate aligner a priori, depending only on the nature of the input sequences. The inference engine was trained on a large set of reference multiple alignments, using a novel machine learning approach. Applying AlexSys to a test set of 178 alignments, we show that the expert system represents a good compromise between alignment quality and running time, making it suitable for high throughput projects. AlexSys is freely available from http://alnitak.u-strasbg.fr/∼aniba/alexsys.

PMID:
20530533
PMCID:
PMC2965243
DOI:
10.1093/nar/gkq526
[Indexed for MEDLINE]
Free PMC Article

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