Autor: |
Meiyappan Lakshmanan, Sean Chia, Kuin Tian Pang, Lyn Chiin Sim, Gavin Teo, Shi Ya Mak, Shuwen Chen, Hsueh Lee Lim, Alison P. Lee, Farouq Bin Mahfut, Say Kong Ng, Yuansheng Yang, Annie Soh, Andy Hee-Meng Tan, Andre Choo, Ying Swan Ho, Terry Nguyen-Khuong, Ian Walsh |
Jazyk: |
angličtina |
Rok vydání: |
2024 |
Předmět: |
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Zdroj: |
Computational and Structural Biotechnology Journal, Vol 23, Iss , Pp 2497-2506 (2024) |
Druh dokumentu: |
article |
ISSN: |
2001-0370 |
DOI: |
10.1016/j.csbj.2024.05.046 |
Popis: |
N-glycosylation can have a profound effect on the quality of mAb therapeutics. In biomanufacturing, one of the ways to influence N-glycosylation patterns is by altering the media used to grow mAb cell expression systems. Here, we explore the potential of machine learning (ML) to forecast the abundances of N-glycan types based on variables related to the growth media. The ML models exploit a dataset consisting of detailed glycomic characterisation of Anti-HER fed-batch bioreactor cell cultures measured daily under 12 different culture conditions, such as changes in levels of dissolved oxygen, pH, temperature, and the use of two different commercially available media. By performing spent media quantitation and subsequent calculation of pseudo cell consumption rates (termed media markers) as inputs to the ML model, we were able to demonstrate a small subset of media markers (18 selected out of 167 mass spectrometry peaks) in a Chinese Hamster Ovary (CHO) cell cultures are important to model N-glycan relative abundances (Regression - correlations between 0.80–0.92; Classification - AUC between 75.0–97.2). The performances suggest the ML models can infer N-glycan critical quality attributes from extracellular media as a proxy. Given its accuracy, we envisage its potential applications in biomaufactucuring, especially in areas of process development, downstream and upstream bioprocessing. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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