Cheng Hsueh-Chien, Angermann Bastian R, Zhang Fengkai, Meier-Schellersheim Martin
Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 4, 4 Memorial Drive, 20892 Bethesda, USA.
BMC Syst Biol. 2014 Jun 16;8:70. doi: 10.1186/1752-0509-8-70.
Network representations of cell-biological signaling processes frequently contain large numbers of interacting molecular and multi-molecular components that can exist in, and switch between, multiple biochemical and/or structural states. In addition, the interaction categories (associations, dissociations and transformations) in such networks cannot satisfactorily be mapped onto simple arrows connecting pairs of components since their specifications involve information such as reaction rates and conditions with regard to the states of the interacting components. This leads to the challenge of having to reconcile competing objectives: providing a high-level overview without omitting relevant information, and showing interaction specifics while not overwhelming users with too much detail displayed simultaneously. This problem is typically addressed by splitting the information required to understand a reaction network model into several categories that are rendered separately through combinations of visualizations and/or textual and tabular elements, requiring modelers to consult several sources to obtain comprehensive insights into the underlying assumptions of the model.
We report the development of an application, the Simmune NetworkViewer, that visualizes biochemical reaction networks using iconographic representations of protein interactions and the conditions under which the interactions take place using the same symbols that were used to specify the underlying model with the Simmune Modeler. This approach not only provides a coherent model representation but, moreover, following the principle of "overview first, zoom and filter, then details-on-demand," can generate an overview visualization of the global network and, upon user request, presents more detailed views of local sub-networks and the underlying reaction rules for selected interactions. This visual integration of information would be difficult to achieve with static network representations or approaches that use scripted model specifications without offering simple but detailed symbolic representations of molecular interactions, their conditions and consequences in terms of biochemical modifications.
The Simmune NetworkViewer provides concise, yet comprehensive visualizations of reaction networks created in the Simmune framework. In the near future, by adopting the upcoming SBML standard for encoding multi-component, multi-state molecular complexes and their interactions as input, the NetworkViewer will, moreover, be able to offer such visualization for any rule-based model that can be exported to that standard.
细胞生物学信号传导过程的网络表示通常包含大量相互作用的分子和多分子成分，这些成分可以存在于多种生化和/或结构状态中，并在这些状态之间切换。此外，此类网络中的相互作用类别（关联、解离和转化）无法令人满意地映射到连接成对成分的简单箭头上，因为它们的规范涉及诸如反应速率和关于相互作用成分状态的条件等信息。这就带来了必须协调相互竞争目标的挑战：提供高层次的概述而不遗漏相关信息，同时展示相互作用的细节而又不会因同时显示过多细节而使用户应接不暇。这个问题通常通过将理解反应网络模型所需的信息分为几类来解决，这些信息通过可视化和/或文本及表格元素的组合分别呈现，这要求建模者查阅多个来源才能全面了解模型的基本假设。
我们报告了一个应用程序Simmune NetworkViewer的开发，它使用蛋白质相互作用的图标表示以及使用与Simmune Modeler用于指定基础模型相同的符号来表示相互作用发生的条件，从而可视化生化反应网络。这种方法不仅提供了连贯的模型表示，而且遵循“先概述，再缩放和过滤，然后按需查看细节”的原则，可以生成全局网络的概述可视化，并根据用户请求呈现局部子网的更详细视图以及所选相互作用的基础反应规则。对于静态网络表示或使用脚本化模型规范而不提供分子相互作用、其条件以及生化修饰方面的简单但详细的符号表示的方法，这种信息的可视化集成很难实现。
Simmune NetworkViewer为在Simmune框架中创建的反应网络提供了简洁而全面的可视化。在不久的将来，通过采用即将推出的用于编码多组分、多状态分子复合物及其相互作用作为输入的SBML标准，NetworkViewer还将能够为任何可以导出到该标准的基于规则的模型提供此类可视化。
