Harnessing the potential of artificial neural networks for predicting protein glycosylation
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Supporting information
Published version
Author(s)
Kotidis, P
Kontoravdi, Kleio
Type
Journal Article
Abstract
Kinetic models offer incomparable insight on cellular mechanisms controlling protein glycosylation. However, their ability to reproduce site-specific glycoform distributions depends on accurate estimation of a large number of protein-specific kinetic parameters and prior knowledge of enzyme and transport protein levels in the Golgi membrane. Herein we propose an artificial neural network (ANN) for protein glycosylation and apply this to four recombinant glycoproteins produced in Chinese hamster ovary (CHO) cells, two monoclonal antibodies and two fusion proteins. We demonstrate that the ANN model accurately predicts site-specific glycoform distributions of up to eighteen glycan species with an average absolute error of 1.1%, correctly reproducing the effect of metabolic perturbations as part of a hybrid, kinetic/ANN, glycosylation model (HyGlycoM), as well as the impact of manganese supplementation and glycosyltransferase knock out experiments as a stand-alone machine learning algorithm. These results showcase the potential of machine learning and hybrid approaches for rapidly developing performance-driven models of protein glycosylation.
Date Issued
2020-06-01
Date Acceptance
2020-05-07
Citation
Metabolic Engineering Communications, 2020, 10
ISSN
2214-0301
Publisher
Elsevier
Journal / Book Title
Metabolic Engineering Communications
Volume
10
Copyright Statement
©2020 The Authors. Published by Elsevier B.V. on behalf of International Metabolic Engineering Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Subjects
Antibody
Artificial neural networks
Chinese hamster ovary cells
Fusion protein
Hybrid modelling
Nucleotide sugars
Protein glycosylation
Publication Status
Published
Article Number
ARTN e00131
Date Publish Online
2020-05-15