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. 2021 Oct 12;10:e69324. doi: 10.7554/eLife.69324

Figure 5. Heatmaps for the intrinsic contribution to the covariance.

These heatmaps estimate the level of overshoot in the pathway-reporter approach for the nascent-protein and mature-protein reporters; blue regions show an overshoot of less than 0.05.

Here, the intrinsic contribution is calculated using stochastic simulations of the model 𝐌4. For the mature-protein and nascent-protein reporters, we consider three different values of the parameter μ, specifically μ=2, μ=10, and μ=20. In all cases, the parameter δp and the on-rate λ are varied between 0.01 and 0.5, and 0.5 and 5, respectively. The parameters of the model 𝐌4 are scaled so that δM=1. The maturation rate is fixed at 20, with the parameters KN and KP chosen to produce a mean protein level of 1000, a mean nascent mRNA level of 5 and a mean mature mRNA level of 50. Each individual pixel is generated from a sample of size 3000, although there is still some instability in the convergence for the nascent-protein reporter, particularly as the overshoot estimation starts to increase, and particularly as μ is larger. To produce more accurate values, the case of μ=2 was averaged over two full experiments while μ=20 was averaged over three. This was also done for the mature-protein reporter, however for these images there was almost no visible difference between the various runs of the experiment and their averages. Each of the three μ values takes approximately 7–10 hr of computation, depending on lead in time before sampling within a simulation. Figure 5—figure supplement 1 gives a heatmap for the overshoot in the pathway-reporter approach for nascent-mature pathway reporters.

Figure 5.

Figure 5—figure supplement 1. Heatmap for the intrinsic contribution to the covariance for nascent-mature pathway reporters.

Figure 5—figure supplement 1.

The nascent-mature reporter concerns only mRNA and so is independent of all protein-related parameters. The heatmap shows the intrinsic contribution for values of λ and μ between 0.1 and 20, with the same parameter selections for KN, KM as in Figure 5 of the main text. Similar simulations for average nascent mRNA levels of 3 and of 8, and mature mRNA levels of 30 and of 160 produced almost identical heatmaps.