Abstract

BackgroundGlycosylation is one of the most complex post-translational modifications (PTMs) of proteins in eukaryotic cells. Glycosylation plays an important role in biological processes ranging from protein folding and subcellular localization, to ligand recognition and cell-cell interactions. Experimental identification of glycosylation sites is expensive and laborious. Hence, there is significant interest in the development of computational methods for reliable prediction of glycosylation sites from amino acid sequences.ResultsWe explore machine learning methods for training classifiers to predict the amino acid residues that are likely to be glycosylated using information derived from the target amino acid residue and its sequence neighbors. We compare the performance of Support Vector Machine classifiers and ensembles of Support Vector Machine classifiers trained on a dataset of experimentally determined N-linked, O-linked, and C-linked glycosylation sites extracted from O-GlycBase version 6.00, a database of 242 proteins from several different species. The results of our experiments show that the ensembles of Support Vector Machine classifiers outperform single Support Vector Machine classifiers on the problem of predicting glycosylation sites in terms of a range of standard measures for comparing the performance of classifiers. The resulting methods have been implemented in EnsembleGly, a web server for glycosylation site prediction.ConclusionEnsembles of Support Vector Machine classifiers offer an accurate and reliable approach to automated identification of putative glycosylation sites in glycoprotein sequences.

Highlights

  • Glycosylation is one of the most complex post-translational modifications (PTMs) of proteins in eukaryotic cells

  • An ensemble of Support Vector Machines outperforms a single Support Vector Machine trained on unbalanced data on the glycosylation site prediction task For each glycosylation type considered in this study, N, O, and C-linked glycosylation, we trained ensembles of Support Vector Machine (SVM) classifiers to predict whether or not a site in a protein sequence is a glycosylation site

  • An ensemble of Support Vector Machines outperforms a single Support Vector Machine trained on balanced data on the glycosylation site prediction task For each glycosylation type considered in this study, N, O, and C-linked glycosylation, we compared the performance of the ensemble of SVM classifiers with that of a single SVM classifier trained on a balanced training set and evaluated on a test set

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Summary

Introduction

Glycosylation is one of the most complex post-translational modifications (PTMs) of proteins in eukaryotic cells. Glycosylation plays an important role in biological processes ranging from protein folding and subcellular localization, to ligand recognition and cell-cell interactions. There is significant interest in the development of computational methods for reliable prediction of glycosylation sites from amino acid sequences. Glycosylation is one of the most complex and ubiquitous post-translational modifications (PTMs) of proteins in eukaryotic cells. It is a dynamic enzymatic process in which saccharides are attached to proteins or lipoproteins, usually on serine (S), threonine (T), asparagine (N), and tryptophan (W) residues. O-GlycBase [16] provides such a dataset for training classifiers for predicting glycosylation sites

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