Glyco-Mapper: A Chinese hamster ovary (CHO) genome-specific glycosylation prediction tool

Abstract

Glyco-Mapper is a novel systems biology product quality prediction tool created using a new framework termed: Discretized Reaction Network Modeling using Fuzzy Parameters (DReaM-zyP). Within Glyco-Mapper, users fix the nutrient feed composition and the glycosylation reaction fluxes to fit the model glycoform to the reference experimental glycoform, enabling cell-line specific glycoform predictions as a result of cell engineering strategies. Glyco-Mapper accurately predicts glycoforms associated with genetic alterations that result in the appearance or disappearance of one or more glycans with an accuracy, sensitivity, and specificity of 96%, 85%, and 97%, respectively, for publications between 1999 and 2014. The modeled glycoforms span a large range of glycoform engineering strategies, including the altered expression of glycosylation, nucleotide sugar transport, and metabolism genes, as well as an altered nutrient feeding strategy. A glycoprotein-producing CHO cell line reference glycoform was modeled and a novel Glyco-Mapper prediction was experimentally confirmed with an accuracy and specificity of 95% and 98%, respectively. Glyco-Mapper is a product quality prediction tool that provides a streamlined way to design host cell line genomes to achieve specific product quality attributes.