{"doi":"10.1371/journal.pone.0175376","title":"Model-based analysis of N-glycosylation in Chinese hamster ovary cells","abstract":null,"journal":"PLOS ONE","year":2017,"id":678161,"datarank":0.5955437870328184,"base_score":3.970291913552122,"endowment":3.970291913552122,"self_citation_contribution":0.5955437870328184,"citation_network_contribution":0.0,"self_endowment_contribution":0.5955437870328184,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":52,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1771898,"name":"Sandra V. Bennun","orcid":null,"position":1,"is_corresponding":false},{"id":1771900,"name":"Mikael R. Andersen","orcid":"0000-0003-4794-6808","position":2,"is_corresponding":false},{"id":227507,"name":"Michael J. Betenbaugh","orcid":"0000-0002-6336-4659","position":3,"is_corresponding":false},{"id":374076,"name":"Frederick J. Krambeck","orcid":"0000-0003-3838-3775","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Model-based analysis of N-glycosylation in Chinese hamster ovary cells","abstract":"The Chinese hamster ovary (CHO) cell is the gold standard for manufacturing of glycosylated recombinant proteins for production of biotherapeutics. The similarity of its glycosylation patterns to the human versions enable the products of this cell line favorable pharmacokinetic properties and lower likelihood of causing immunogenic responses. Because glycan structures are the product of the concerted action of intracellular enzymes, it is difficult to predict a priori how the effects of genetic manipulations alter glycan structures of cells and therapeutic properties. For that reason, quantitative models able to predict glycosylation have emerged as promising tools to deal with the complexity of glycosylation processing. For example, an earlier version of the same model used in this study was used by others to successfully predict changes in enzyme activities that could produce a desired change in glycan structure. In this study we utilize an updated version of this model to provide a comprehensive analysis of N-glycosylation in ten Chinese hamster ovary (CHO) cell lines that include a wild type parent and nine mutants of CHO, through interpretation of previously published mass spectrometry data. The updated N-glycosylation mathematical model contains up to 50,605 glycan structures. Adjusting the enzyme activities in this model to match N-glycan mass spectra produces detailed predictions of the glycosylation process, enzyme activity profiles and complete glycosylation profiles of each of the cell lines. These profiles are consistent with biochemical and genetic data reported previously. The model-based results also predict glycosylation features of the cell lines not previously published, indicating more complex changes in glycosylation enzyme activities than just those resulting directly from gene mutations. The model predicts that the CHO cell lines possess regulatory mechanisms that allow them to adjust glycosylation enzyme activities to mitigate side effects of the primary loss or gain of glycosylation function known to exist in these mutant cell lines. Quantitative models of CHO cell glycosylation have the potential for predicting how glycoengineering manipulations might affect glycoform distributions to improve the therapeutic performance of glycoprotein products.","is_dataset_classified":null,"base_score":3.970291913552122,"endowment":3.970291913552122,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"28486471","pmcid":"PMC5423595","openalex_id":"https://openalex.org/W2613429086","authors":[],"funders":[{"funder_name":"Division of Cancer Prevention, National Cancer Institute","grant_id":"5R41CA127885-02","title":"Mathematical model relating gene expression to glycoform structure"},{"funder_name":"Scripps Howard Foundation","grant_id":"U54-GM062116","title":null},{"funder_name":"NCI NIH HHS","grant_id":"R41 CA127885","title":null},{"funder_name":"NIGMS NIH HHS","grant_id":"U54 GM062116","title":null},{"funder_name":"National Institutes of Health","grant_id":"1U54GM062116-01A1","title":"PILOT--ANTIGENS AND T CELL RECOGNITION OF CARBOHYDRATES"}],"total_grants":5,"fwci":1.5201,"citation_percentile":0.82317753,"influential_citations":0,"citation_trend":[{"year":2017,"count":1},{"year":2018,"count":3},{"year":2019,"count":3},{"year":2020,"count":8},{"year":2021,"count":13},{"year":2022,"count":6},{"year":2023,"count":7},{"year":2024,"count":8},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0175376&type=printable","host_type":"journal"},{"url":"https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0175376&type=printable","host_type":"publisher"},{"url":"http://dx.plos.org/10.1371/journal.pone.0175376","host_type":"publisher"},{"url":"https://doi.org/10.1371/journal.pone.0175376","host_type":"journal"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5423595","host_type":"repository"},{"url":"https://pubmed.ncbi.nlm.nih.gov/28486471","host_type":"repository"},{"url":"https://doaj.org/article/a94ecdf3b214402693c109aa1083d56c","host_type":"repository"},{"url":"https://figshare.com/articles/dataset/Model-based_analysis_of_N-glycosylation_in_Chinese_hamster_ovary_cells/4987406","host_type":"repository"},{"url":"https://orbit.dtu.dk/en/publications/b07b66c3-9b3c-42d5-8350-78cf6f0092cb","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC5423595","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC5423595?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1371/journal.pone.0175376","host_type":""},{"url":"https://dx.doi.org/10.1371/journal.pone.0175376","host_type":""},{"url":"https://backend.orbit.dtu.dk/ws/files/132506501/pone.0175376.pdf","host_type":""}],"fields_of_study":["Glycosylation and Glycoproteins Research","Viral Infectious Diseases and Gene Expression in Insects","Monoclonal and Polyclonal Antibodies Research","0301 basic medicine","03 medical and health sciences","Animals","CHO Cells","Cricetinae","Cricetulus","Enzymes","Glycosylation","Models, Biological","Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization"],"mesh_terms":["Animals","Cricetulus","Enzymes","Glycosylation","Cricetinae","Models, Biological","CHO Cells","Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization"],"keywords":["Chinese hamster ovary cell","Glycosylation","Glycan","Biology","N-linked glycosylation","Mutant","Computational biology","Biochemistry","Cell culture","Glycoprotein","Genetics","Gene","Science","Q","R","CHO Cells","Models, Biological","Enzymes","Cricetulus","Cricetinae","Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization","Medicine","Animals","Research Article"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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