Jeong Euna, Nagasaki Masao, Saito Ayumu, Miyano Satoru
Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan.
In Silico Biol. 2007;7(6):623-38.
With the rapidly accumulating knowledge of biological entities and networks, there is a growing need for a general framework to understand this information at a system level. In order to understand life as system, a formal description of system dynamics with semantic validation will be necessary. Within the context of biological pathways, several formats have been proposed, e.g., SBML, CellML, and BioPAX. Unfortunately, these formats lack the formal definitions of each term or fail to capture the system dynamics behavior. Thus, we have developed a new system dynamics centered ontology called Cell System Ontology (CSO). As an exchange format, the ontology is implemented in the Web Ontology Language (OWL), which enables semantic validation and automatic reasoning to check the consistency of biological pathway models. The features of CSO are as follows: (1) manipulation of different levels of granularity and abstraction of pathways, e.g., metabolic pathways, regulatory pathways, signal transduction pathways, and cell-cell interactions; (2) capture of both quantitative and qualitative aspects of biological function by using hybrid functional Petri net with extension (HFPNe); and (3) encoding of biological pathway data related to visualization and simulation, as well as modeling. The new ontology also predefines mature core vocabulary, which will be necessary for creating models with system dynamics. In addition, each of the core terms has at least one standard icon for easy modeling and accelerating the exchangeability among applications. In order to demonstrate the potential of CSO-based pathway modeling, visualization, and simulation, we present an HFPNe model for the ASEL and ASER regulatory networks in Caenorhabditis elegans.
随着生物实体和网络知识的迅速积累，越来越需要一个通用框架来在系统层面理解这些信息。为了将生命理解为一个系统，需要对系统动力学进行形式化描述并进行语义验证。在生物途径的背景下，已经提出了几种格式，例如SBML、CellML和BioPAX。不幸的是，这些格式缺乏对每个术语的形式化定义，或者未能捕捉系统动力学行为。因此，我们开发了一种新的以系统动力学为中心的本体，称为细胞系统本体（CSO）。作为一种交换格式，该本体是用网络本体语言（OWL）实现的，它能够进行语义验证和自动推理，以检查生物途径模型的一致性。CSO的特点如下：（1）对不同粒度和抽象层次的途径进行操作，例如代谢途径、调控途径、信号转导途径和细胞间相互作用；（2）通过使用扩展混合功能Petri网（HFPNe）来捕捉生物功能的定量和定性方面；（3）对与可视化、模拟以及建模相关的生物途径数据进行编码。新本体还预先定义了成熟的核心词汇表，这对于创建具有系统动力学的模型是必要的。此外，每个核心术语都至少有一个标准图标，以便于建模并加速应用程序之间的可交换性。为了展示基于CSO的途径建模、可视化和模拟的潜力，我们提出了一个关于秀丽隐杆线虫ASEL和ASER调控网络的HFPNe模型。
