Hemmerich Johannes, Tenhaef Niklas, Wiechert Wolfgang, Noack Stephan
Institute of Bio- and Geosciences - IBG-1: Biotechnology Forschungszentrum Jülich GmbH Jülich Germany.
Computational Systems Biotechnology (AVT.CSB) RWTH Aachen University Aachen Germany.
Eng Life Sci. 2021 Jan 6;21(3-4):242-257. doi: 10.1002/elsc.202000088. eCollection 2021 Mar.
Quantitative characterization of biotechnological production processes requires the determination of different key performance indicators (KPIs) such as titer, rate and yield. Classically, these KPIs can be derived by combining black-box bioprocess modeling with non-linear regression for model parameter estimation. The presented pyFOOMB package enables a guided and flexible implementation of bioprocess models in the form of ordinary differential equation systems (ODEs). By building on Python as powerful and multi-purpose programing language, ODEs can be formulated in an object-oriented manner, which facilitates their modular design, reusability, and extensibility. Once the model is implemented, seamless integration and analysis of the experimental data is supported by various Python packages that are already available. In particular, for the iterative workflow of experimental data generation and subsequent model parameter estimation we employed the concept of replicate model instances, which are linked by common sets of parameters with global or local properties. For the description of multi-stage processes, discontinuities in the right-hand sides of the differential equations are supported via event handling using the freely available assimulo package. Optimization problems can be solved by making use of a parallelized version of the generalized island approach provided by the pygmo package. Furthermore, pyFOOMB in combination with Jupyter notebooks also supports education in bioprocess engineering and the applied learning of Python as scientific programing language. Finally, the applicability and strengths of pyFOOMB will be demonstrated by a comprehensive collection of notebook examples.
生物技术生产过程的定量表征需要确定不同的关键绩效指标(KPI),如滴度、速率和产量。传统上,这些KPI可以通过将黑箱生物过程建模与用于模型参数估计的非线性回归相结合来推导。本文介绍的pyFOOMB软件包能够以常微分方程系统(ODE)的形式对生物过程模型进行有指导且灵活的实现。通过以强大的多用途编程语言Python为基础,ODE可以以面向对象的方式进行公式化,这有利于其模块化设计、可重用性和可扩展性。一旦模型实现,各种现有的Python软件包将支持对实验数据进行无缝集成和分析。特别是,对于实验数据生成和后续模型参数估计的迭代工作流程,我们采用了复制模型实例的概念,这些实例通过具有全局或局部属性的公共参数集进行链接。对于多阶段过程的描述,可通过使用免费的assimulo软件包进行事件处理来支持微分方程右侧的不连续性。优化问题可以通过使用pygmo软件包提供的广义岛方法的并行化版本来解决。此外,pyFOOMB与Jupyter笔记本相结合还支持生物过程工程教育以及将Python作为科学编程语言的应用学习。最后,将通过一系列全面的笔记本示例来展示pyFOOMB的适用性和优势。