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Bioinformatics Advance Access published online on April 7, 2005
Bioinformatics, doi:10.1093/bioinformatics/bti432
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© The Author (2005). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received December 26, 2004
Revised April 4, 2005
Accepted April 4, 2005

Article

Use of multiple profiles corresponding to a sequence alignment enables effective detection of remote homologues

B. Anand 1, V. S. Gowri 1, and N. Srinivasan 1*

1 Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India

* To whom correspondence should be addressed.
N. Srinivasan, E-mail: ns{at}mbu.iisc.ernet.in


  Abstract

Motivation: Position Specific Scoring Matrices (PSSMs) corresponding to aligned sequences of homologous proteins are commonly used in homology detection. A PSSM is generated on the basis of one of the homologues as a reference sequence, which is the query in the case of PSI_BLAST searches. Reference sequence is chosen arbitrarily while generating PSSMs for reverse BLAST searches. In this work we demonstrate that use of multiple PSSMs corresponding to a given alignment and variable reference sequences is more effective than using traditional single PSSMs and Hidden Markov Models.

Results: Searches for proteins with known 3-D structure have been made against three databases of protein family profiles corresponding to known structures: (1) One PSSM per family (2) Multiple PSSMs corresponding to an alignment and variable reference sequences for every family and (3) Hidden Markov Models. Comparative performance of these three approaches suggests that use of multiple PSSMs is most effective.


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