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BMC Bioinformatics

, 10:335

First Online: 15 October 2009Received: 14 February 2009Accepted: 15 October 2009

Abstract

BackgroundThe number of protein family members defined by DNA sequencing is usually much larger than those characterised experimentally. This paper describes a method to divide protein families into subtypes purely on sequence criteria. Comparison with experimental data allows an independent test of the quality of the clustering.

ResultsAn evolutionary split statistic is calculated for each column in a protein multiple sequence alignment; the statistic has a larger value when a column is better described by an evolutionary model that assumes clustering around two or more amino acids rather than a single amino acid. The user selects columns typically the top ranked columns to construct a motif. The motif is used to divide the family into subtypes using a stochastic optimization procedure related to the deterministic annealing EM algorithm DAEM, which yields a specificity score showing how well each family member is assigned to a subtype. The clustering obtained is not strongly dependent on the number of amino acids chosen for the motif. The robustness of this method was demonstrated using six well characterized protein families: nucleotidyl cyclase, protein kinase, dehydrogenase, two polyketide synthase domains and small heat shock proteins. Phylogenetic trees did not allow accurate clustering for three of the six families.

ConclusionThe method clustered the families into functional subtypes with an accuracy of 90 to 100%. False assignments usually had a low specificity score.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2105-10-335 contains supplementary material, which is available to authorized users.

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Author: Pavle Goldstein - Jurica Zucko - Dušica Vujaklija - Anita Kriško - Daslav Hranueli - Paul F Long - Catherine Etchebest -

Source: https://link.springer.com/







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