Effect of Catalyticity on Noise.

<p><b>A)</b> Simulation results for noise as a function of and . Inset: analytical results for the same system. Parameters same as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072676#pone-0072676-g001" target="_blank">Figure 1</a> with . <b>B)</b> Maximum of noise in the crossover regime as a function of . Inset: Same result shown using analytical method for larger range of parameters showing the plateau (unaccessable computationally due to large particle numbers). <b>C)</b> Noise in the repressed regime as a function of for constant protein mean (). Inset: protein mean as a function of .</p

ceRNA Hypothesis.

<p><b>A)</b> Schematic of mRNA crosstalk through a shared pool of microRNAs. stand for transcription rate of each mRNA and correspond to interaction rates between mRNA and microRNA. The other interactions are as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072676#pone-0072676-g001" target="_blank">Figure 1A</a>. <b>B,C)</b> Gillespie results for protein mean (B) and noise (C) as a function of transcription rates of the two mRNAs with equal . Parameters same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072676#pone-0072676-g001" target="_blank">Figure 1</a> with . <b>D,E)</b> Gillespie results for protein mean (D) and noise (E) as a function of transcription rates of the two mRNAs with unequal . Parameters same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072676#pone-0072676-g001" target="_blank">Figure 1</a> with . Noise surface plots have been smoothed and interpolated for better visibillity. <b>F)</b> LNA results for noise of two non-identical species as a function of normalized transcription rates (with ). All the parameters are chosen to be distinct, i.e. .</p

mRNA Decay.

<p>Time-course of mean mRNA number showing different decay rates in different parameter regimes. Each curve is the average of 100 Gillespie simulations with the same initial conditions starting at steady state of the unregulated model (). Parameters same as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072676#pone-0072676-g001" target="_blank">Figure 1</a> with .</p

Scaling at Crossover Regime.

<p>Parameters same as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072676#pone-0072676-g001" target="_blank">Figure 1</a> with . <b>A)</b> Protein noise normalized to its value at (more explicitly ) plotted as a function of for . Each line is a different value of . Same legend for all figures. <b>B)</b> Protein mean normalized to its value at (more explicitly )plotted as a function of for . <b>C,D)</b> Graphs similar to <b>A,B</b> plotted for . <b>E,F)</b> Graphs similar to <b>A,B</b> plotted for .</p

mRNA Decay in ceRNA hypothesis.

<p>Time-course of mean mRNA number (first species) while transcription rate and interaction rate of the other species is being changed. Each curve is the average of 100 Gillespie simulations with the same initial conditions at steady state of unregulated system (). For both species parameters are the same as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072676#pone-0072676-g001" target="_blank">Figure 1</a> with with the exception of the parameter under study. <b>A)</b> Time course of mRNA as transcritption rate of the competing mRNA is changed. <b>B)</b> Time course of mRNA as interaction rate of the competing mRNA is changed.</p

ceRNA Error.

<p>Figure showing the percentage of difference between LNA results and Gillespie results in the ceRNA hypothesis calculated as <b>A,B)</b> Error of protein mean (A) and noise (B) as a function of transcription rates of the two mRNAs with equal .Parameters same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072676#pone-0072676-g008" target="_blank">Figure 8B</a>. <b>C,D)</b> Error of protein mean (C) and noise (D) as a function of transcription rates of the two mRNAs with unequal . Parameters same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072676#pone-0072676-g008" target="_blank">Figure 8D</a>.</p

Qualitative Robustness of Mean and Noise.

<p>First and second row show analytical results for protein mean and noise respectively as a function of while in each column one single parameter is varied. Third row is analytical results for protein noise calculated at and plotted as a function of the parameter under study. Parameters that are not changed in each graph are the same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072676#pone-0072676-g001" target="_blank">Figure 1</a>.</p

Scaling at Crossover Regime (Simulation Results).

<p>Parameters same as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072676#pone-0072676-g001" target="_blank">Figure 1</a> with . Data has been smoothed using a moving average method. <b>A)</b> Protein noise normalized to its value at (more explicitly ) plotted as a function of for . Each line is a different value of . Same legend for all figures. <b>B)</b> Protein mean normalized to its value at (more explicitly ) plotted as a function of for . <b>C,D)</b> Graphs similar to <b>A,B</b> plotted for . <b>E,F)</b> Graphs similar to <b>A,B</b> plotted for .</p

Catalyticity and Bursting.

<p>Noise in the repressed regime with bursting as a function of for constant protein mean. For each data point is chosen such that . Furthermore . The remaining parameters are same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072676#pone-0072676-g001" target="_blank">Figure 1</a> with . Inset: protein mean as a function of .</p

Protein Noise in Two Regimes.

<p>Gillespie simulation results showing protein noise as a function of mean protein concentration for stoichiometric and catalytic interactions plotted for two different values of interaction rate . For each value of catalytic interaction has a slightly higher noise in the crossover regime compared to stoichiometric interaction, otherwise a similar three-regime behavior can be observed in both cases. We have plotted this result for two different values of to show that this observation is qualitatively independent of interaction strength, and only affects the level of noise. Parameters same as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0072676#pone-0072676-g001" target="_blank">Figure 1B</a>. Stoichiometric regime with and catalytic regime with .</p