细胞生命过程数学刻画建模

Mathematical modelling for cellular processes

摘要:

生物制造是使用工程细胞实现化学品、医药、能源、材料产品的规模化生产，也是应对全球环境危机，实现“双碳”目标，推动经济社会绿色转型的一种新兴生产力。高效设计并构建工程细胞需要精准、全面的数字细胞模型。测序仪、质谱、光谱、微流控等前沿装备的迭代升级，数据科学、人工智能、自动化等高新技术集群的突破性进展，使得细胞组分动态变化的精确测量、海量生物数据的快速获取、细胞过程数理模型的精准构建成为可能。本文系统归纳了系统生物学中细胞建模的数理框架：首先从网络拓扑、随机过程、动力学方程等维度剖析了常见数学模型架构及其使用范围，继而分类评述了生长分裂、形态发生、DNA复制、转录调控、生化代谢、信号转导、群体感应等单一细胞过程的建模策略，重点探讨了整合多个细胞过程构建全细胞模型的研究进展，最后讨论了数据不足、机制解析不充分、多维数据整合困难、计算复杂度指数增长等限制细胞生命过程数学刻画的若干关键挑战。本文汇总了系统生物学中细胞生命过程精确模拟的数理基础，增进了对细胞运作分子机制的理解，对未来工程生物的设计与构建具有重要意义。

关键词:生物制造;细胞生命过程;数学模型;系统生物学;全细胞模型

Abstract:

Biomanufacturing harnesses engineered cells for the large-scale production of biochemicals, biopharmaceuticals, biofuels, and biomaterials, playing a vital role in mitigating global environmental crises, achieving carbon peaking and neutrality, and driving the green transformation of the economy and society. The effective design and construction of these engineered cells require precise and comprehensive computational models. Recent technological breakthroughs including high-throughput sequencing, mass spectrometry, spectroscopy, and microfluidic devices, coupled with advances in data science, artificial intelligence, and automation, have enabled the rapid acquisition of large-scale biological datasets, thereby facilitating a deeper understanding of cellular dynamics and the construction of mechanism-based models with enhanced accuracy. This review systematically summarises the mathematical frameworks employed in cellular modelling. It begins by evaluating prevalent mathematical paradigms, such as network topology analyses, stochastic processes, and kinetic equations, critically assessing their applicability across various contexts. The discussion then categorises modelling strategies for specific cellular processes, including cellular growth and division, morphogenesis, DNA replication, transcriptional regulation, metabolism, signal transduction, and quorum sensing. We also examine the recent progress in developing whole-cell models through the integration of diverse cellular processes. The review concludes by addressing key challenges such as data scarcity, unknown mechanisms, multi-dimensional data integration, and exponentially escalating computational complexity. Overall, this work consolidates the mathematical models for the precise simulation of cellular processes, thereby enhancing our understanding of the molecular mechanisms governing cellular functions and contributing to the future design and optimisation of engineered organisms.

Key words:biomanufacturing;cellular process;mathematical modelling;systems biology;whole-cell model