Machine Learning-Powered Optimization of a CHO Cell Cultivation Process

IF 3.5 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Jannik Richter, Qimin Wang, Ferdinand Lange, Phil Thiel, Nina Yilmaz, Dörte Solle, Xiaoying Zhuang, Sascha Beutel
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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.

Abstract Image

Abstract Image

CHO细胞培养过程的机器学习优化。
中国仓鼠卵巢(CHO)细胞是最广泛用于生产重组治疗性蛋白如单克隆抗体(mab)的细胞系。然而,CHO细胞培养过程的优化是非常复杂的,受多种因素的影响。本研究探讨了使用机器学习(ML)算法来优化已建立的工业CHO细胞培养过程。使用人工神经网络(ANN)形式的ML算法,并对历史和新生成的CHO细胞培养数据集进行训练。然后使用该算法寻找更好的培养条件并提高细胞生产率。所选择的人工智能(AI)工具能够建议优化的培养设置和新的条件组合,从而保证增加细胞生长和提高单抗滴度。经过验证实验表明,ML算法能够成功优化培养过程,显著提高抗体产量。最佳结果显示,最终单抗滴度提高了48%,这表明使用ML算法是一种很有前途的方法,可以清楚地优化CHO细胞培养过程等生物过程的生产力。
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来源期刊
Biotechnology and Bioengineering
Biotechnology and Bioengineering 工程技术-生物工程与应用微生物
CiteScore
7.90
自引率
5.30%
发文量
280
审稿时长
2.1 months
期刊介绍: Biotechnology & Bioengineering publishes Perspectives, Articles, Reviews, Mini-Reviews, and Communications to the Editor that embrace all aspects of biotechnology. These include: -Enzyme systems and their applications, including enzyme reactors, purification, and applied aspects of protein engineering -Animal-cell biotechnology, including media development -Applied aspects of cellular physiology, metabolism, and energetics -Biocatalysis and applied enzymology, including enzyme reactors, protein engineering, and nanobiotechnology -Biothermodynamics -Biofuels, including biomass and renewable resource engineering -Biomaterials, including delivery systems and materials for tissue engineering -Bioprocess engineering, including kinetics and modeling of biological systems, transport phenomena in bioreactors, bioreactor design, monitoring, and control -Biosensors and instrumentation -Computational and systems biology, including bioinformatics and genomic/proteomic studies -Environmental biotechnology, including biofilms, algal systems, and bioremediation -Metabolic and cellular engineering -Plant-cell biotechnology -Spectroscopic and other analytical techniques for biotechnological applications -Synthetic biology -Tissue engineering, stem-cell bioengineering, regenerative medicine, gene therapy and delivery systems The editors will consider papers for publication based on novelty, their immediate or future impact on biotechnological processes, and their contribution to the advancement of biochemical engineering science. Submission of papers dealing with routine aspects of bioprocessing, description of established equipment, and routine applications of established methodologies (e.g., control strategies, modeling, experimental methods) is discouraged. Theoretical papers will be judged based on the novelty of the approach and their potential impact, or on their novel capability to predict and elucidate experimental observations.
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