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Bioinformatics Advance Access originally published online on September 6, 2007
Bioinformatics 2007 23(18):2361-2367; doi:10.1093/bioinformatics/btm358
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© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

The global trace graph, a novel paradigm for searching protein sequence databases

Andreas Heger 1,{dagger}, Swapan Mallick 1,{ddagger}, Christopher Wilton 1,§ and Liisa Holm 1,2,*

1Institute of Biotechnology and 2Department of Biological and Environmental Sciences, Division of Genetics, P.O. Box 56 (Viikinkaari 5), FI-00014 University of Helsinki, Finland

*To whom correspondence should be addressed.


  Abstract

Motivation: Propagating functional annotations to sequence-similar, presumably homologous proteins lies at the heart of the bioinformatics industry. Correct propagation is crucially dependent on the accurate identification of subtle sequence motifs that are conserved in evolution. The evolutionary signal can be difficult to detect because functional sites may consist of non-contiguous residues while segments in-between may be mutated without affecting fold or function.

Results: Here, we report a novel graph clustering algorithm in which all known protein sequences simultaneously self-organize into hypothetical multiple sequence alignments. This eliminates noise so that non-contiguous sequence motifs can be tracked down between extremely distant homologues. The novel data structure enables fast sequence database searching methods which are superior to profile-profile comparison at recognizing distant homologues. This study will boost the leverage of structural and functional genomics and opens up new avenues for data mining a complete set of functional signature motifs.

Availability: http://www.bioinfo.biocenter.helsinki.fi/gtg

Contact: liisa.holm{at}helsinki.fi

Supplementary information: Supplementary data are available at Bioinformatics online.

Associate Editor: Burkhard Rost

{dagger}Present address: MRC Functional Genetics Unit, Department of Physiology, Anatomy & Genetics, University of Oxford, South Parks Road, OX1 3QX Oxford, UK.

{ddagger}Present address: Department of Gernetics, Harvard Medical School, Boston, MA, USA.

§Present address: Babraham Institute, Cambridge, UK.

Received on March 8, 2007; revised on June 11, 2007; accepted on July 5, 2007

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A. Heger, E. Korpelainen, T. Hupponen, K. Mattila, V. Ollikainen, and L. Holm
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Nucleic Acids Res., January 11, 2008; 36(suppl_1): D276 - D280.
[Abstract] [Full Text] [PDF]


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