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Bioinformatics Advance Access published online on May 3, 2005
Bioinformatics, 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@oupjournals.org
Received January 9, 2005
Revised March 21, 2005
Accepted April 21, 2005

Article

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*

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


  Abstract

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

Results: The local alignment of conserved blocks (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 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 (COMPASS and Prof_sim) and a sequence-to-profile (PSI-Blast) methods. The testing was large-scale and used several parameters, including pseudo-counts profile calculations and the use of 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-bin/LAMA_search_new.sh.


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