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From in vivo to in silico biology and back

Abstract

The massive acquisition of data in molecular and cellular biology has led to the renaissance of an old topic: simulations of biological systems. Simulations, increasingly paired with experiments, are being successfully and routinely used by computational biologists to understand and predict the quantitative behaviour of complex systems, and to drive new experiments. Nevertheless, many experimentalists still consider simulations an esoteric discipline only for initiates. Suspicion towards simulations should dissipate as the limitations and advantages of their application are better appreciated, opening the door to their permanent adoption in everyday research.

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Figure 1: Simulation of a simple network using different mathematical formalisms.
Figure 2: Example of mathematical-formalism-independent pitfalls in modelling.
Figure 3: Effect of localization of species on cellular processes.
Figure 4: Example of putative model-dependent pitfalls in modelling: continuous versus discrete concentrations.
Figure 5: Example of synthetic gene networks built with defined behaviour.

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Acknowledgements

We thank J. Reich, J. J. Collins, I. Mattaj and J. Gagneur for critical reading of the manuscript, and P. Beltrao and M. Isalan for helpful discussions. This work was financed partly by the EC grant, COMBIO.

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Supplementary Notes

This file contains Supplementary Figures, (summarizing the constraint-based modelling approach) and Supplementary Discussion (gives details about the simulation (for example, reaction network, parameters) for each model discussed in the main text), and gives a detailed mathematical analysis for the model discussed in Figure 2. (DOC 500 kb)

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Di Ventura, B., Lemerle, C., Michalodimitrakis, K. et al. From in vivo to in silico biology and back. Nature 443, 527–533 (2006). https://doi.org/10.1038/nature05127

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