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Nucleic Acids Research, 2002, Vol. 30, No. 7 1575-1584
© 2002 Oxford University Press

An efficient algorithm for large-scale detection of protein families

A. J. Enright*, S. Van Dongen1 and C. A. Ouzounis

Computational Genomics Group, The European Bioinformatics Institute, EMBL Cambridge Outstation, Cambridge CB10 1SD, UK and 1Centrum voor Wiskunde en Informatica, Kruislaan 413, NL-1098 SJ Amsterdam, The Netherlands

Detection of protein families in large databases is one of the principal research objectives in structural and functional genomics. Protein family classification can significantly contribute to the delineation of functional diversity of homologous proteins, the prediction of function based on domain architecture or the presence of sequence motifs as well as comparative genomics, providing valuable evolutionary insights. We present a novel approach called TRIBE-MCL for rapid and accurate clustering of protein sequences into families. The method relies on the Markov cluster (MCL) algorithm for the assignment of proteins into families based on precomputed sequence similarity information. This novel approach does not suffer from the problems that normally hinder other protein sequence clustering algorithms, such as the presence of multi-domain proteins, promiscuous domains and fragmented proteins. The method has been rigorously tested and validated on a number of very large databases, including SwissProt, InterPro, SCOP and the draft human genome. Our results indicate that the method is ideally suited to the rapid and accurate detection of protein families on a large scale. The method has been used to detect and categorise protein families within the draft human genome and the resulting families have been used to annotate a large proportion of human proteins.

* To whom correspondence should be addressed. Tel: +44 1223 494452; Fax: +44 1223 494468; Email: anton{at}ebi.ac.uk


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Nucleic Acids ResHome page
R. L. Marsden, D. Lee, M. Maibaum, C. Yeats, and C. A. Orengo
Comprehensive genome analysis of 203 genomes provides structural genomics with new insights into protein family space
Nucleic Acids Res., February 15, 2006; 34(3): 1066 - 1080.
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Mol Biol EvolHome page
J. M. Duarte, L. Cui, P. K. Wall, Q. Zhang, X. Zhang, J. Leebens-Mack, H. Ma, N. Altman, and C. W. dePamphilis
Expression Pattern Shifts Following Duplication Indicative of Subfunctionalization and Neofunctionalization in Regulatory Genes of Arabidopsis
Mol. Biol. Evol., February 1, 2006; 23(2): 469 - 478.
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Nucleic Acids ResHome page
I. Uchiyama
Hierarchical clustering algorithm for comprehensive orthologous-domain classification in multiple genomes
Nucleic Acids Res., January 25, 2006; 34(2): 647 - 658.
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Nucleic Acids ResHome page
C. Yeats, M. Maibaum, R. Marsden, M. Dibley, D. Lee, S. Addou, and C. A. Orengo
Gene3D: modelling protein structure, function and evolution
Nucleic Acids Res., January 1, 2006; 34(suppl_1): D281 - D284.
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Nucleic Acids ResHome page
F. Chen, A. J. Mackey, C. J. Stoeckert Jr, and D. S. Roos
OrthoMCL-DB: querying a comprehensive multi-species collection of ortholog groups
Nucleic Acids Res., January 1, 2006; 34(suppl_1): D363 - D368.
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Nucleic Acids ResHome page
S. Hartmann, D. Lu, J. Phillips, and T. J. Vision
Phytome: a platform for plant comparative genomics
Nucleic Acids Res., January 1, 2006; 34(suppl_1): D724 - D730.
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Mol Biol EvolHome page
R. P. Olinski, L.-G. Lundin, and F. Hallbook
Conserved Synteny Between the Ciona Genome and Human Paralogons Identifies Large Duplication Events in the Molecular Evolution of the Insulin-Relaxin Gene Family
Mol. Biol. Evol., January 1, 2006; 23(1): 10 - 22.
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Mol Biol EvolHome page
S. Kim, P. S. Soltis, K. Wall, and D. E. Soltis
Phylogeny and Domain Evolution in the APETALA2-like Gene Family
Mol. Biol. Evol., January 1, 2006; 23(1): 107 - 120.
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Phil Trans R Soc BHome page
M. Blaxter, J. Mann, T. Chapman, F. Thomas, C. Whitton, R. Floyd, and E. Abebe
Defining operational taxonomic units using DNA barcode data
Phil Trans R Soc B, October 29, 2005; 360(1462): 1935 - 1943.
[Abstract] [Full Text] [PDF]



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