{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:03:23Z","timestamp":1787583803813,"version":"build-2736575974"},"reference-count":42,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biotechnology Journal"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Precise control of critical quality attributes, including titer and glycosylation, is essential in bioprocessing, yet conventional design\u2011of\u2011experiments methods are challenged by the high\u2010dimensional, nonlinear design space for media and process parameters. We assemble a comprehensive glycan\u2011focused Chinese hamster ovary (CHO) fed\u2011batch dataset and develop a computational workflow (i) to train machine learning (ML) models to predict key CQAs, (ii) apply a hybrid ML\u00a0+\u00a0knowledge\u2010based strategy to select potentially impactful features, and (iii) generate combinatorial media designs. The resulting models predict final titer (\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u00a0\u2248\u00a00.93) and major glycan metrics\u2014mannosylation, fucosylation, galactosylation (\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u00a0\u2248\u00a00.79\u20130.95)\u2014directly from initial media composition and process parameters without requiring spent media analysis. Feature selection shortlisted 20 features out of 76 for a second\u2010tier validation, from which 15 were confirmed as actionable levers impacting titer and glycosylation, uncovering glycan effects independent of nucleotide sugar supplementation. Finally, we incorporated our workflow, utilizing a ML surrogate model coupled with simulated annealing, in a proof\u2011of\u2011concept active learning step, successfully proposing a media composition and process parameter combination that reduced mannosylation by 10% while increasing titer. Together, these results underscore how ML\u2011enhanced DOE can accelerate CHO process development and explore complex biomanufacturing spaces with greater efficiency.\n                  <\/jats:p>","DOI":"10.1002\/biot.70149","type":"journal-article","created":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T10:20:11Z","timestamp":1761906011000},"source":"Crossref","is-referenced-by-count":6,"title":["Toward Machine Learning\u2010Guided CHO Bioprocess and Media Optimization for Improved Titer and Glycosylation"],"prefix":"10.1002","volume":"20","author":[{"given":"Ian","family":"Walsh","sequence":"first","affiliation":[{"name":"Bioprocessing Technology Institute, A*STAR, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumi","family":"Shozui","sequence":"additional","affiliation":[{"name":"Ajinomoto Co., Inc.  Chuo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayaka","family":"Sato","sequence":"additional","affiliation":[{"name":"Ajinomoto Co., Inc.  Chuo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uiseon","family":"Park","sequence":"additional","affiliation":[{"name":"Ajinomoto CELLiST Korea Co., Inc., Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeran","family":"Cho","sequence":"additional","affiliation":[{"name":"Ajinomoto CELLiST Korea Co., Inc., Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8840-9104","authenticated-orcid":false,"given":"Charmaine","family":"Chia","sequence":"additional","affiliation":[{"name":"Bioprocessing Technology Institute, A*STAR, Singapore"},{"name":"Bioinformatics Institute, A*STAR, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/antib9020022"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2020.00622"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2016.01.006"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.25450"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.26904"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616-024-00690-7"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10616\u2010025\u201000733\u20107"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2020.03.009"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1753\u20106561\u20109\u2010S9\u2010P15"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/btpr.67"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.202100228"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00362\u2010023\u201001437\u2010w"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010024\u201083581\u20103"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201039022\u20102"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44286\u2010024\u201000099\u20101"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44172\u2010024\u201000322\u20100"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41524\u2010019\u20100153\u20108"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-49775-z"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/fermentation10050234"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1080\/19420862.2021.2013593"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coche.2021.100690"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2017.01.005"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.202000261"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2023.108179"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biotechadv.2022.108008"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2024.05.046"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.08.27.609988"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2024.1441885"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41540\u2010023\u201000284\u20107"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bej.2024.109591"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.28943"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.614324"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.200500052"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/269305"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2005.02.003"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbiotec.2005.02.003"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.27140"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.21141"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00253\u2010025\u201013405\u20105"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.27496"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/biot.202100098"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymben.2022.12.009"}],"container-title":["Biotechnology 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