Haydarlou Reza, Jacobsen Annika, Bonzanni Nicola, Feenstra K Anton, Abeln Sanne, Heringa Jaap
Centre for Integrative Bioinformatics (IBIVU) & Amsterdam Institute for Molecules Medicines and Systems (AIMMS), VU University Amsterdam, De Boelelaan 1081, Amsterdam, The Netherlands.
Centre for Integrative Bioinformatics (IBIVU) & Amsterdam Institute for Molecules Medicines and Systems (AIMMS), VU University Amsterdam, De Boelelaan 1081, Amsterdam, The Netherlands NKI-AVL, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, The Netherlands.
Bioinformatics. 2016 Jun 15;32(12):i60-i69. doi: 10.1093/bioinformatics/btw250.
Biological pathways play a key role in most cellular functions. To better understand these functions, diverse computational and cell biology researchers use biological pathway data for various analysis and modeling purposes. For specifying these biological pathways, a community of researchers has defined BioPAX and provided various tools for creating, validating and visualizing BioPAX models. However, a generic software framework for simulating BioPAX models is missing. Here, we attempt to fill this gap by introducing a generic simulation framework for BioPAX. The framework explicitly separates the execution model from the model structure as provided by BioPAX, with the advantage that the modelling process becomes more reproducible and intrinsically more modular; this ensures natural biological constraints are satisfied upon execution. The framework is based on the principles of discrete event systems and multi-agent systems, and is capable of automatically generating a hierarchical multi-agent system for a given BioPAX model.
To demonstrate the applicability of the framework, we simulated two types of biological network models: a gene regulatory network modeling the haematopoietic stem cell regulators and a signal transduction network modeling the Wnt/β-catenin signaling pathway. We observed that the results of the simulations performed using our framework were entirely consistent with the simulation results reported by the researchers who developed the original models in a proprietary language.
The framework, implemented in Java, is open source and its source code, documentation and tutorial are available at http://www.ibi.vu.nl/programs/BioASF CONTACT: j.heringa@vu.nl.
生物途径在大多数细胞功能中起着关键作用。为了更好地理解这些功能,不同的计算生物学和细胞生物学研究人员将生物途径数据用于各种分析和建模目的。为了指定这些生物途径,一个研究团队定义了BioPAX,并提供了各种用于创建、验证和可视化BioPAX模型的工具。然而,缺少一个用于模拟BioPAX模型的通用软件框架。在这里,我们试图通过引入一个用于BioPAX的通用模拟框架来填补这一空白。该框架将执行模型与BioPAX提供的模型结构明确分开,其优点是建模过程变得更具可重复性且本质上更具模块化;这确保了在执行时满足自然的生物学约束。该框架基于离散事件系统和多智能体系统的原理,并且能够为给定的BioPAX模型自动生成一个分层多智能体系统。
为了证明该框架的适用性,我们模拟了两种类型的生物网络模型:一种是模拟造血干细胞调节因子的基因调控网络,另一种是模拟Wnt/β-连环蛋白信号通路的信号转导网络。我们观察到,使用我们的框架进行模拟的结果与使用专有语言开发原始模型的研究人员报告的模拟结果完全一致。
该框架用Java实现,是开源的,其源代码、文档和教程可在http://www.ibi.vu.nl/programs/BioASF获取。