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Transmembrane protein topology prediction using support vector machines

Nugent, T; Jones, DT; (2009) Transmembrane protein topology prediction using support vector machines. BMC BIOINFORMATICS , 10 , Article 159. 10.1186/1471-2105-10-159. Green and gold open access

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Abstract

Background: Alpha-helical transmembrane (TM) proteins are involved in a wide range of important biological processes such as cell signaling, transport of membrane-impermeable molecules, cell-cell communication, cell recognition and cell adhesion. Many are also prime drug targets, and it has been estimated that more than half of all drugs currently on the market target membrane proteins. However, due to the experimental difficulties involved in obtaining high quality crystals, this class of protein is severely under-represented in structural databases. In the absence of structural data, sequence-based prediction methods allow TM protein topology to be investigated.Results: We present a support vector machine-based (SVM) TM protein topology predictor that integrates both signal peptide and re-entrant helix prediction, benchmarked with full cross-validation on a novel data set of 131 sequences with known crystal structures. The method achieves topology prediction accuracy of 89%, while signal peptides and re-entrant helices are predicted with 93% and 44% accuracy respectively. An additional SVM trained to discriminate between globular and TM proteins detected zero false positives, with a low false negative rate of 0.4%. We present the results of applying these tools to a number of complete genomes. Source code, data sets and a web server are freely available from http://bioinf.cs.ucl.ac.uk/psipred/.Conclusion: The high accuracy of TM topology prediction which includes detection of both signal peptides and re-entrant helices, combined with the ability to effectively discriminate between TM and globular proteins, make this method ideally suited to whole genome annotation of alpha-helical transmembrane proteins.

Type:Article
Title:Transmembrane protein topology prediction using support vector machines
Open access status:An open access publication. A version is also available from UCL Discovery.
DOI:10.1186/1471-2105-10-159
Publisher version:http://dx.doi.org/10.1186/1471-2105-10-159
Language:English
Additional information:© 2009 Nugent and Jones; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords:INTEGRAL MEMBRANE-PROTEINS, SIGNAL PEPTIDES, DATA-BANK, EVOLUTIONARY INFORMATION, SECONDARY STRUCTURE, COMPLETE GENOMES, BATTEN-DISEASE, WEB SERVER, CLASSIFICATION, DATABASE
UCL classification:UCL > School of BEAMS > Faculty of Engineering Science > Computer Science

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