Conceptual modeling in systems biology fosters empirical findings: the mRNA lifecycle

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 biologica...

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Bibliographic Details
Published in:PloS one 2007-09, Vol.2 (9), p.e872-e872
Main Authors: Dori, Dov, Choder, Mordechai
Format: Article
Language:English
Subjects:
Analysis
Baking yeast
Biodegradation
Biological evolution
Biology
Cell Biology/Gene Expression
Cell interactions
Communications systems
Computational Biology/Systems Biology
Cytoplasm
Empirical Research
Enzymes
Genomes
Life cycle analysis
Life sciences
Messenger RNA
Modelling
Models, Theoretical
Proteins
Regulation
RNA polymerase
RNA transport
RNA, Messenger - genetics
RNA, Messenger - physiology
Saccharomyces cerevisiae
Studies
Systems Biology
Transcription
Translation
Translation (Genetics)
Translation termination
Yeasts
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0000872