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Bioinformatics Advance Access published online on August 20, 2007
Bioinformatics, doi:10.1093/bioinformatics/btm355
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© The Author (2007). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Methods of remote homology detection can be combined to increase coverage by 10% in the midnight zone

Adam James Reid *, Corin Yeats and Christine Anne Orengo

Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK

*To whom correspondence should be addressed. Adam James Reid, E-mail: reid{at}biochem.ucl.ac.uk


  Abstract

Motivation: A recent development in sequence-based remote homologue detection is the introduction of profile-profile comparison methods. These are more powerful than previous technologies and can detect potentially homologous relationships missed by structural classifications such as CATH and SCOP. As structural classifications traditionally act as the gold standard of homology this poses a challenge in benchmarking them.

Results: We present a novel approach which allows an accurate benchmark of these methods against the CATH structural classification. We then apply this approach to assess the accuracy of a range of publicly available methods for remote homology detection including several profile-profile methods (COMPASS, HHSearch, PRC) from two perspectives. Firstly in distinguishing homologous domains from non-homologues and secondly in annotating proteomes with structural domain families. PRC is shown to be the best method for distinguishing homologues. We show that SAM is the best practical method for annotating genomes, whilst using COMPASS for the most remote homologues would increase coverage. Finally we introduce a simple approach to increase the sensitivity of remote homologue detection by up to 10%. This is achieved by combining multiple methods with a jury vote.

Associate Editor: Prof. Dmitrij Frishman

Received on April 17, 2007; revised on June 12, 2007; accepted on July 3, 2007

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