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基于机器学习的CHO细胞培养过程优化

Machine Learning-Powered Optimization of a CHO Cell Cultivation Process.

作者信息

Richter Jannik, Wang Qimin, Lange Ferdinand, Thiel Phil, Yilmaz Nina, Solle Dörte, Zhuang Xiaoying, Beutel Sascha

机构信息

Institute of Technical Chemistry, Faculty of Natural Sciences, Leibniz University Hannover, Hannover, Germany.

Institute of Photonics, Faculty of Mathematics and Physics, Leibniz University Hannover, Hannover, Germany.

出版信息

Biotechnol Bioeng. 2025 May;122(5):1153-1164. doi: 10.1002/bit.28943. Epub 2025 Jan 31.

Abstract

Chinese Hamster Ovary (CHO) cells are the most widely used cell lines to produce recombinant therapeutic proteins such as monoclonal antibodies (mAbs). However, the optimization of the CHO cell culture process is very complex and influenced by various factors. This study investigates the use of machine learning (ML) algorithms to optimize an established industrial CHO cell cultivation process. A ML algorithm in the form of an artificial neural network (ANN) was used and trained on datasets from historical and newly generated CHO cell cultivation runs. The algorithm was then used to find better cultivation conditions and improve cell productivity. The selected artificial intelligence (AI) tool was able to suggest optimized cultivation settings and new condition combinations, which promised both increased cell growth and increased mAb titers. After performing the validation experiments, it was shown that the ML algorithm was able to successfully optimize the cultivation process and significantly improve the antibody production. The best results showed an increase in final mAb titer up to 48%, demonstrating that the use of ML algorithms is a promising approach to optimize the productivity of bioprocesses like CHO cell cultivation processes clearly.

摘要

中国仓鼠卵巢(CHO)细胞是生产重组治疗性蛋白(如单克隆抗体)最广泛使用的细胞系。然而,CHO细胞培养过程的优化非常复杂,且受多种因素影响。本研究调查了使用机器学习(ML)算法优化已建立的工业CHO细胞培养过程。采用了人工神经网络(ANN)形式的ML算法,并在来自历史和新生成的CHO细胞培养运行的数据集上进行训练。然后使用该算法找到更好的培养条件并提高细胞生产力。所选的人工智能(AI)工具能够提出优化的培养设置和新的条件组合,有望同时提高细胞生长和单克隆抗体滴度。进行验证实验后,结果表明ML算法能够成功优化培养过程并显著提高抗体产量。最佳结果显示最终单克隆抗体滴度提高了48%,表明使用ML算法显然是优化如CHO细胞培养过程等生物过程生产力的一种有前景的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c45c/11975184/9994918e5dcf/BIT-122-1153-g001.jpg

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