Glycosylation prediction tool

We evaluated SPRINT-Gly against consensus-based model as well as previous methods by submitting protein sequence entries from our independent test set to publicly accessible web servers. Logarithmic plots to clearly illustrate the regions with low false positive rates are also shown for N -linked sites in Supplementary Figure S3.

Here, we developed a machine-learning approach to predict N- and O- linked glycosylation sites in human and mouse glycoproteins. To improve the accuracy of our models, we constructed a glycosylation-site repository by merging data from six data resources, and integrated protein sequence and structure-based features to train deep neural network and SVM models. We have shown that the N- glycosylation model performs equally well for intra or cross-species datasets, however, the O- glycosylation models performs poorly for cross-species tests, indicating the species difference in O -glycosylation mechanism.

The dataset collected in this work is the largest available for predicting N- and O- linked glycosylation sites by machine learning. Previously, GlycoPP Chauhan et al. EnsembleGly Caragea et al. For N- linked sites, both human and mouse proteins were predicted with high sensitivity and precision. These results suggest that our predictions of N- linked sites are approaching experimental accuracy. This performance can be explained by the training set size, the implementation of DNN, and an expanded list of protein sequence and structural features such as orientation-dependent contact numbers HSE.

More data are needed to improve training. SPRINT-Gly will continue to expand and develop in conjunction with data deposited in UniCarbKB, which will improve the quality of the training datasets thereby improving the accuracy of the models discussed. By integrating such data and leveraging advancements in machine-learning SPRINT-Gly provides a unique and powerful approach for the prediction of potential glycosylation sites, which will have an impact on understanding the biological importance of glycosylation.

We also acknowledge the authors of previous methods for providing the webservers. Abadi M. Google Scholar. Google Preview. Aebi M. Trends Biochem. Altschul S. Nucleic Acids Res. Apweiler R. Beltrao P. Ben-Dor S. Glycobiology , 14 , 95 — Blom N. Proteomics , 4 , Campbell M.

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Wang S. N-linked glycosylation refers to the attachment of oligosaccharides to a nitrogen atom, usually the N4 of asparagine residues. N-glycosylation occurs on secreted or membrane bound proteins, mainly in eukaryotes and archaea - most bacteria do not carry out this modification. In eukaryotes, N-glycosylation begins as a co-translational event in the endoplasmic reticulum, where preassembled blocks of 14 sugars including 2 N-acetylglucosamines, 9 mannoses and 3 glucoses are first added to the nascent polypeptide chain.

After cleavage of 3 glucose and 1 mannose residues, the protein is transferred to the Golgi apparatus where the glycans lose a variable number of mannose residues and acquire a more complex structure during a process called 'terminal glycosylation'. If the type of N-linked glycan is known, it is indicated in the 'Description' field using the terms 'high mannose', 'hybrid' or 'complex'.

Examples: P , P Predicted sites are only annotated in regions of proteins that are known or predicted to be extracellular, and are tagged as 'Sequence Analysis' Sequence model. In general, we avoid propagating N-glycosylation sites 'By similarity' to related proteins. Example: Q94BT2. O-linked glycosylation of secreted and membrane bound proteins is a post-translational event that takes place in the cis-Golgi compartment after N-glycosylation and folding of the protein.

It refers to the attachment of glycans to serine and threonine, and, to a lesser extent, to hydroxyproline and hydroxylysine. O-linked glycans play important roles in protein localization and trafficking, protein solubility, antigenicity and cell-cell interactions. O-linked glycans are built up in a stepwise fashion with sugars added incrementally. The most common type of O-glycosylation in secreted and membrane-bound mammalian proteins seems to be the addition of reducing terminal N-acetylgalactosamine GalNAc.

This type of O-linked glycan is also referred to as 'mucin-type' glycan. The reducing terminal GalNAc residue can be further extended with galactose Gal , N-acetylglucosamine GlcNAc or GlcNAc and Gal resulting in 8 common core structures, which are often further decorated with the addition of up to three sialic acid residues.

Example: P In addition to the mucin-type O-linked glycans, a variety of mammalian proteins are known to have mannose Man , fucose Fuc , glucose Glc , Gal or xylose Xyl as reducing terminal linkages. Some cytoplasmic and nuclear proteins have simple O-linked glycans in which a single N-acetylglucosamine residue is linked to a serine or a threonine.

This modification has been identified in a number of eukaryotes including plants and filamentous fungi, although its presence in S. This type of O-linked glycosylation plays an important role in the modulation of the biological activity of intracellular proteins; in some proteins the same residue may be subject to competing phosphorylation and O-linked glycosylation.

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