Whole-cell modeling aims to incorporate all main genes and processes, and their interactions of a cell in one model. Whole-cell modeling has been regarded as the central aim of systems biology but also as a grand challenge, which plays essential roles in current and future systems biology. In this paper, we analyze whole-cell modeling challenges and requirements and classify them into three aspects (or dimensions): heterogeneous biochemical networks, uncertainties in components, and representation of cell structure. We then explore how to use different Petri net classes to address different aspects of whole-cell modeling requirements. Based on these analyses, we present a Petri nets-based framework for whole-cell modeling, which not only addresses many whole-cell modeling requirements, but also offers a graphical, modular, and hierarchical modeling tool. We think this framework can offer a feasible modeling approach for whole-cell model construction.

全细胞建模旨在将所有主要基因和过程以及它们在一个模型中的细胞相互作用结合起来。全细胞建模已被视为系统生物学的中心目标，同时也是一项重大挑战，在当前和未来的系统生物学中发挥着重要作用。在本文中，我们分析了全细胞建模的挑战和要求，并将它们分为三个方面（或维度）：异构生化网络、组件的不确定性和细胞结构的表示。然后，我们探讨如何使用不同的 Petri 网类来解决全细胞建模要求的不同方面。基于这些分析，我们提出了一个基于 Petri 网的全细胞建模框架，它不仅解决了许多全细胞建模要求，还提供了图形化、模块化、和分层建模工具。我们认为该框架可以为全细胞模型构建提供一种可行的建模方法。