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Bioinformatics Advance Access originally published online on May 3, 2005
Bioinformatics 2005 21(13):2950-2956; doi:10.1093/bioinformatics/bti462
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© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions{at}oupjournals.org

Enhanced statistics for local alignment of multiple alignments improves prediction of protein function and structure

Milana Frenkel-Morgenstern 1, Hillary Voet 2 and Shmuel Pietrokovski 1,*

1Department of Molecular Genetics, Weizmann Institute of Science Rehovot 76100, Israel
2Agriculture Faculty, Hebrew University Rehovot 76100, Israel

*To whom correspondence should be addressed.

Motivation: Improved comparisons of multiple sequence alignments (profiles) with other profiles can identify subtle relationships between protein families and motifs significantly beyond the resolution of sequence-based comparisons.

Results: The local alignment of multiple alignments (LAMA) method was modified to estimate alignment score significance by applying a new measure based on Fisher's combining method. To verify the new procedure, we used known protein structures, sequence annotations and cyclical relations consistency analysis (CYRCA) sets of consistently aligned blocks. Using the new significance measure improved the sensitivity of LAMA without altering its selectivity. The program performed better than other profile-to-profile methods (COMPASS and Prof_sim) and a sequence-to-profile method (PSI-BLAST). The testing was large scale and used several parameters, including pseudo-counts profile calculations and local ungapped blocks or more extended gapped profiles. This comparison provides guidelines to the relative advantages of each method for different cases. We demonstrate and discuss the unique advantages of using block multiple alignments of protein motifs.

Availability: http://bioinformatics.weizmann.ac.il/blocks/LAMA

Contact: shmuel.pietrokovski{at}weizmann.ac.il


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Home page
 Nucleic Acids ResHome page
R. I. Sadreyev and N. V. Grishin
Accurate statistical model of comparison between multiple sequence alignments
Nucleic Acids Res., April 1, 2008; 36(7): 2240 - 2248.
[Abstract] [Full Text] [PDF]


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