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Birch, E. W., Ruggero, N. A., & Covert, M. W. (2012). Determining Host Metabolic Limitations on Viral Replication via Integrated Modeling and Experimental Perturbation. PLoS Computational Biology, 8(10), e1002746. doi:10.1371/journal.pcbi.1002746 (2012)
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Viral replication relies on host metabolic machinery and precursors to produce large numbers of progeny - often very rapidly. A fundamental example is the infection of Escherichia coli by bacteriophage T7. The resource draw imposed by viral replication represents a significant and complex perturbation to the extensive and interconnected network of host metabolic pathways. To better understand this system, we have integrated a set of structured ordinary differential equations quantifying T7 replication and an E. coli flux balance analysis metabolic model. Further, we present here an integrated simulation algorithm enforcing mutual constraint by the models across the entire duration of phage replication. This method enables quantitative dynamic prediction of virion production given only specification of host nutritional environment, and predictions compare favorably to experimental measurements of phage replication in multiple environments. The level of detail of our computational predictions facilitates exploration of the dynamic changes in host metabolic fluxes that result from viral resource consumption, as well as analysis of the limiting processes dictating maximum viral progeny production. For example, although it is commonly assumed that viral infection dynamics are predominantly limited by the amount of protein synthesis machinery in the host, our results suggest that in many cases metabolic limitation is at least as strict. Taken together, these results emphasize the importance of considering viral infections in the context of host metabolism.


Provides the simulation code used in published integration of phage T7 ODEs and E. coli FBA.

License: t7phagefba

The associated publication described the integration of T7 phage viral replication Ordinary Differential Equations with host E. coli metabolic Flux Balance Analysis such that the two models interact and constrain one another over the time course of infection and virion synthesis. This code runs the simulations and produces the results figure panels in the publication.

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Provides: the flat files and model specific functions describing the particular models used (.text and MatLab formats); the modular and generalizable functions defining the simulation integration method developed (MatLab formats); and the parsers and visualization functions (MatLab formats and R) that produce the publication associated figures.

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