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A Comprehensive Computational Model of Mycoplasma Genitalium

Jayodita Sanghvi, Jonathan R. Karr, Jared Jacobs and Markus W. Covert, Bioengineering, Stanford University, Stanford, CA

A major challenge in the field of systems biology is to build a computational model of all the cellular processes in a living cell. A whole cell model will provide a better understanding of cellular physiology as well as multifaceted behaviors such as complex disease states. It may also serve as a predictive tool to guide cellular engineering and synthetic biology. However, such developments have been challenged by the limitations of current methods and lack of adequate databases. We have developed the first comprehensive model of the lifecycle of a single living cell that simulates all known gene functions. We have created a novel modeling approach that represents different biological functions as separate modules that are each implemented with different mathematical representations. Our model system is Mycoplasma genitalium, the bacterium with the smallest known self-replicating genome. The model incorporates the cross talk between all of the cellular processes including metabolism, transcription, translation, replication, and cell division. It has been validated and benchmarked against existing physiological data. The resulting simulations predict cell behavior in response to genomic and environmental perturbations as well as phenotypes that lead to questions that have never before been addressed.

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