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We describe Dizzy, a software tool for stochastically and deterministically modeling the spatially homogeneous kinetics of integrated large-scale genetic, metabolic, and signaling networks. Notable features include a modular simulation framework, reusable modeling elements, complex kinetic rate laws, multi-step reaction processes, steady-state noise(More)
Transcriptional noise is known to be an important cause of cellular heterogeneity and phenotypic variation. The extent to which molecular interaction networks may have evolved to either filter or exploit transcriptional noise is a much debated question. The yeast genetic network regulating galactose metabolism involves two proteins, Gal3p and Gal80p, that(More)
Nonlinear dynamical models are frequently used to approximate and predict observed physical, biological, and economic systems. Such models will be subject to errors both in the model dynamics, and the observations of the underlying system. In order to improve models, it is necessary to understand the causes of error growth. A complication with chaotic(More)
The average number of mRNA molecules per active gene in yeast can be remarkably low. Consequently, the relative number of copies of each transcript per cell can vary greatly from moment to moment. When these transcripts are encoding metabolic enzymes, how do the resulting variations in enzyme concentrations affect the regulation of metabolic intermediates?(More)
Error in weather forecasting is due to inaccuracy both in the models used, and in the estimate of the current atmospheric state at which the model is initiated. Because weather models are thought to be chaotic, and therefore sensitive to initial condition, the technique of ensemble forecasting has been developed in part to address the latter effect. An(More)
Ovarian function was studied in 18 female patients treated for abdominal tumours during childhood. All received abdominal radiotherapy as part of their treatment and were studied between 1 and 26 years after irradiation. The serum gonadotrophins and oestradiol levels were consistent with ovarian failure in each case but there was a disproportionate(More)
Computer modelling and simulation are commonly used to analyse engineered systems. Biological systems differ in that they often cannot be accurately characterised, so simulations are far from exact. Nonetheless, we argue in this paper that evolution results in recurring, dynamic organisational principles in biological systems, and that simulation can help(More)
Positive and negative feedback loops, for example, where a protein regulates its own transcription, play an important role in many genetic regulatory networks. Such systems will be subject to internal noise, which occurs due to the small number of molecules taking part in some reactions. This paper examines the effect of feedback loops on noise levels.(More)
Transcriptional noise is known to play a crucial role in heterogeneity in bacteria and yeast. Mammalian macrophages are known to exhibit cell-to-cell variation in their responses to pathogens, but the source of this heterogeneity is not known. We have developed a detailed stochastic model of gene expression that takes into account scaling effects due to(More)