Abstract
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.
Highlights
Recent years have witnessed unprecedented increases in the number, variety and complexity of information resources available to researchers in the life sciences
This pivotal time for the life sciences is captured by the words of Kitano: ‘‘a transition is occurring in biology from the molecular level to the system level that promises to revolutionize our understanding of complex biological regulatory systems and to provide major new opportunities for practical application of such knowledge’’ [1]
We have applied Object-Process Methodology to create a conceptual model of the mRNA lifecycle
Summary
Recent years have witnessed unprecedented increases in the number, variety and complexity of information resources available to researchers in the life sciences. We are at a turning point in biological research, where emphasis is shifting from the study of a single molecular process to studying complete cellular pathways and the entire cell as a system This pivotal time for the life sciences is captured by the words of Kitano: ‘‘a transition is occurring in biology from the molecular level to the system level that promises to revolutionize our understanding of complex biological regulatory systems and to provide major new opportunities for practical application of such knowledge’’ [1]. There is a drive to acquire system-level comprehension of the countless pieces of information that have been gathered thanks to decades of meticulous laboratory research by thousands of scientists These efforts, many of which are currently considered as contributions to Systems Biology, are aimed at understanding the underlying structure and behavior of biological systems at the molecular, cellular, organism, and habitat levels. Kitano [1] noted that new tools, ranging from experimental devices to software and analytical methods, are required if we are to meet the challenges of systems biology
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