Conceptual Modeling in Systems Biology Fosters Empirical Findings: The mRNA Lifecycle
Conceptual Modeling in Systems Biology Fosters Empirical Findings: The mRNA Lifecycle
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DOI：
10.1371/journal.pone.0000872
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发表时间：
2007-09-12
期刊：
影响因子：
3.7
通讯作者：
Choder, Mordechai
中科院分区：
文献类型：
--
作者：
Dori, Dov;Choder, Mordechai
理解复杂生物系统的主要障碍之一是信息的范围和快速演变，远远超出了个人管理和理解的能力。当前的建模方法和工具缺乏足够的能力来同时建模生物系统的结构和行为。在这里，我们提出了对象过程方法论（OPM），这是一种整体概念建模范式，作为一种在任何所需数量的细节级别上以图解和文本形式对生物系统进行正式和直观建模的方法。 OPM 以一种简单且易于研究人员和学者理解的方式将对象（例如蛋白质）和过程（例如转录）结合起来。作为一个恰当的例子，我们对酵母 mRNA 生命周期进行了建模。 mRNA生命周期涉及mRNA在细胞核中的合成、mRNA转运至细胞质以及随后在细胞质中的翻译和降解。最近的研究已经确定了特定的细胞质焦点，称为加工体，其中含有大型 mRNA 和衰变因子复合物。我们在此提出的该细胞子系统的 OPM 模型导致了这些复合物的新成分的发现，即翻译终止因子 eRF3。在长期饥饿期后观察到 eRF3 与加工体的关联。我们认为 OPM 最终可以作为整个活细胞系统的综合进化模型。该模型将作为一个研究和交流平台，突出未知和不确定的方面，这些方面可以凭经验解决，并在保持一致性的同时进行相应更新。
One of the main obstacles to understanding complex biological systems is the extent and rapid evolution of information, way beyond the capacity individuals to manage and comprehend. Current modeling approaches and tools lack adequate capacity to model concurrently structure and behavior of biological systems. Here we propose Object-Process Methodology (OPM), a holistic conceptual modeling paradigm, as a means to model both diagrammatically and textually biological systems formally and intuitively at any desired number of levels of detail. OPM combines objects, e.g., proteins, and processes, e.g., transcription, in a way that is simple and easily comprehensible to researchers and scholars. As a case in point, we modeled the yeast mRNA lifecycle. The mRNA lifecycle involves mRNA synthesis in the nucleus, mRNA transport to the cytoplasm, and its subsequent translation and degradation therein. Recent studies have identified specific cytoplasmic foci, termed processing bodies that contain large complexes of mRNAs and decay factors. Our OPM model of this cellular subsystem, presented here, led to the discovery of a new constituent of these complexes, the translation termination factor eRF3. Association of eRF3 with processing bodies is observed after a long-term starvation period. We suggest that OPM can eventually serve as a comprehensive evolvable model of the entire living cell system. The model would serve as a research and communication platform, highlighting unknown and uncertain aspects that can be addressed empirically and updated consequently while maintaining consistency.