Computation and Neural Systems, California Institute of Technology, Pasadena, California, United States of America.
Control and Dynamical Systems, California Institute of Technology, Pasadena, California, United States of America.
PLoS Comput Biol. 2022 Apr 20;18(4):e1009987. doi: 10.1371/journal.pcbi.1009987. eCollection 2022 Apr.
Biochemical interactions in systems and synthetic biology are often modeled with chemical reaction networks (CRNs). CRNs provide a principled modeling environment capable of expressing a huge range of biochemical processes. In this paper, we present a software toolbox, written in Python, that compiles high-level design specifications represented using a modular library of biochemical parts, mechanisms, and contexts to CRN implementations. This compilation process offers four advantages. First, the building of the actual CRN representation is automatic and outputs Systems Biology Markup Language (SBML) models compatible with numerous simulators. Second, a library of modular biochemical components allows for different architectures and implementations of biochemical circuits to be represented succinctly with design choices propagated throughout the underlying CRN automatically. This prevents the often occurring mismatch between high-level designs and model dynamics. Third, high-level design specification can be embedded into diverse biomolecular environments, such as cell-free extracts and in vivo milieus. Finally, our software toolbox has a parameter database, which allows users to rapidly prototype large models using very few parameters which can be customized later. By using BioCRNpyler, users ranging from expert modelers to novice script-writers can easily build, manage, and explore sophisticated biochemical models using diverse biochemical implementations, environments, and modeling assumptions.
生物系统和合成生物学中的生化相互作用通常使用化学反应网络 (CRN) 进行建模。CRN 提供了一种原则性的建模环境，能够表达广泛的生化过程。在本文中，我们提出了一个用 Python 编写的软件工具箱，它将使用生化部件、机制和上下文的模块化库表示的高级设计规范编译为 CRN 实现。这个编译过程有四个优点。首先，实际的 CRN 表示的构建是自动的，并输出与众多模拟器兼容的系统生物学标记语言 (SBML) 模型。其次，模块化生化组件库允许用设计选择简洁地表示不同的生化电路架构和实现，这些选择会自动在底层 CRN 中传播。这可以防止在高级设计和模型动态之间经常出现的不匹配。第三，高级设计规范可以嵌入到各种生物分子环境中，例如无细胞提取物和体内环境。最后，我们的软件工具箱具有参数数据库，允许用户使用很少的参数快速原型化大型模型，这些参数可以在以后进行定制。通过使用 BioCRNpyler，从专家建模人员到新手脚本编写人员的用户都可以轻松地使用各种生化实现、环境和建模假设来构建、管理和探索复杂的生化模型。
