Bioinformatics Advance Access originally published online on April 7, 2005
Bioinformatics 2005 21(12):2821-2826; doi:10.1093/bioinformatics/bti432
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Use of multiple profiles corresponding to a sequence alignment enables effective detection of remote homologues

Molecular Biophysics Unit, Indian Institute of Science Bangalore 560 012, India
*To whom correspondence should be addressed.
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. The reference sequence is chosen arbitrarily while generating PSSMs for reverse BLAST searches. In this work we demonstrate that the 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 structures 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. A comparison of the performances of these three approaches suggests that the use of multiple PSSMs is most effective.
Contact: ns{at}mbu.iisc.ernet.in
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