Unstructured modeling and RNN Surrogate development for optimizing vaccine production in Baculovirus Expression Vector System

Surbhi Sharma, K. N. Pujari, S. Miriyala, L. Giri, K. Mitra
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引用次数: 1

Abstract

Process optimization and scale up for biomolecules/vaccine production remain challenging due to the adaptation of experiment-based route which needs a large number of expensive experiments making it more challenging in translating the compound for industrial production. In this context, we propose a framework amalgamating systems biology and artificial intelligence for control and optimization of the protein/vaccine production in a Baculovirus expression system [BEVs]. Experimental investigation is conducted to study the growth of insect cells (Sf-9) when infected with the wild type Baculovirus (AcMNPV). Optimal unstructured model replicating the experimental data on cell and virus growth has been identified using a computation strategy consisting of a hybrid optimization technique. The selected model is then used for large scale data generation with an objective to build AI based RNN model that can be proved extremely helpful to handle numerical stability related issues while performing optimal control of the biological system. This work shows a proof of concept and represents the first instance, where an experimental study, mathematical modeling and AI based techniques have been applied for optimal protein production in recombinant expression system at industry setting.
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杆状病毒表达载体系统中优化疫苗生产的非结构化建模和RNN代理开发
生物分子/疫苗生产的工艺优化和规模扩大仍然具有挑战性,因为基于实验的路线需要大量昂贵的实验,这使得将化合物转化为工业生产更具挑战性。在此背景下,我们提出了一个结合系统生物学和人工智能的框架,用于控制和优化杆状病毒表达系统[bev]中的蛋白质/疫苗生产。本实验研究了野生型杆状病毒(AcMNPV)侵染昆虫细胞(Sf-9)后的生长情况。利用混合优化技术的计算策略,确定了复制细胞和病毒生长实验数据的最优非结构化模型。然后将所选模型用于大规模数据生成,目的是建立基于人工智能的RNN模型,该模型可被证明对处理数值稳定性相关问题非常有帮助,同时对生物系统进行最优控制。这项工作展示了概念验证,并代表了第一个实例,其中实验研究、数学建模和基于人工智能的技术已应用于工业环境下重组表达系统的最佳蛋白质生产。
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