A tree-based conservation scoring method for short linear motifs in multiple alignments of protein sequences

<p>Abstract</p> <p>Background</p> <p>The structure of many eukaryotic cell regulatory proteins is highly modular. They are assembled from globular domains, segments of natively disordered polypeptides and short linear motifs. The latter are involved in protein interacti...

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Main Authors: López Rodrigo, Gould Cathryn M, Labarga Alberto, Chica Claudia, Gibson Toby J
Format: Article
Language:English
Published: BMC 2008-05-01
Series:BMC Bioinformatics
Online Access:http://www.biomedcentral.com/1471-2105/9/229
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author López Rodrigo
Gould Cathryn M
Labarga Alberto
Chica Claudia
Gibson Toby J
author_facet López Rodrigo
Gould Cathryn M
Labarga Alberto
Chica Claudia
Gibson Toby J
author_sort López Rodrigo
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>The structure of many eukaryotic cell regulatory proteins is highly modular. They are assembled from globular domains, segments of natively disordered polypeptides and short linear motifs. The latter are involved in protein interactions and formation of regulatory complexes. The function of such proteins, which may be difficult to define, is the aggregate of the subfunctions of the modules. It is therefore desirable to efficiently predict linear motifs with some degree of accuracy, yet sequence database searches return results that are not significant.</p> <p>Results</p> <p>We have developed a method for scoring the conservation of linear motif instances. It requires only primary sequence-derived information (e.g. multiple alignment and sequence tree) and takes into account the degenerate nature of linear motif patterns. On our benchmarking, the method accurately scores 86% of the known positive instances, while distinguishing them from random matches in 78% of the cases. The conservation score is implemented as a real time application designed to be integrated into other tools. It is currently accessible via a Web Service or through a graphical interface.</p> <p>Conclusion</p> <p>The conservation score improves the prediction of linear motifs, by discarding those matches that are unlikely to be functional because they have not been conserved during the evolution of the protein sequences. It is especially useful for instances in non-structured regions of the proteins, where a domain masking filtering strategy is not applicable.</p>
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spelling doaj.art-eaaf13e5d8e34af59e53a62a59c639492022-12-22T01:06:55ZengBMCBMC Bioinformatics1471-21052008-05-019122910.1186/1471-2105-9-229A tree-based conservation scoring method for short linear motifs in multiple alignments of protein sequencesLópez RodrigoGould Cathryn MLabarga AlbertoChica ClaudiaGibson Toby J<p>Abstract</p> <p>Background</p> <p>The structure of many eukaryotic cell regulatory proteins is highly modular. They are assembled from globular domains, segments of natively disordered polypeptides and short linear motifs. The latter are involved in protein interactions and formation of regulatory complexes. The function of such proteins, which may be difficult to define, is the aggregate of the subfunctions of the modules. It is therefore desirable to efficiently predict linear motifs with some degree of accuracy, yet sequence database searches return results that are not significant.</p> <p>Results</p> <p>We have developed a method for scoring the conservation of linear motif instances. It requires only primary sequence-derived information (e.g. multiple alignment and sequence tree) and takes into account the degenerate nature of linear motif patterns. On our benchmarking, the method accurately scores 86% of the known positive instances, while distinguishing them from random matches in 78% of the cases. The conservation score is implemented as a real time application designed to be integrated into other tools. It is currently accessible via a Web Service or through a graphical interface.</p> <p>Conclusion</p> <p>The conservation score improves the prediction of linear motifs, by discarding those matches that are unlikely to be functional because they have not been conserved during the evolution of the protein sequences. It is especially useful for instances in non-structured regions of the proteins, where a domain masking filtering strategy is not applicable.</p>http://www.biomedcentral.com/1471-2105/9/229
spellingShingle López Rodrigo
Gould Cathryn M
Labarga Alberto
Chica Claudia
Gibson Toby J
A tree-based conservation scoring method for short linear motifs in multiple alignments of protein sequences
BMC Bioinformatics
title A tree-based conservation scoring method for short linear motifs in multiple alignments of protein sequences
title_full A tree-based conservation scoring method for short linear motifs in multiple alignments of protein sequences
title_fullStr A tree-based conservation scoring method for short linear motifs in multiple alignments of protein sequences
title_full_unstemmed A tree-based conservation scoring method for short linear motifs in multiple alignments of protein sequences
title_short A tree-based conservation scoring method for short linear motifs in multiple alignments of protein sequences
title_sort tree based conservation scoring method for short linear motifs in multiple alignments of protein sequences
url http://www.biomedcentral.com/1471-2105/9/229
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