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First, the extremely stochastic nature of evolution renders such precision immensely difficult (Fig. 1).
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Once samples are extremely diluted, stochastic events may lead to variations in the number of molecules of a certain transcript in aliquots of the same RNA preparation.
Two most important nonlinear processes, which are not possible to be incorporated into the transfer function by approximation, exist in this pathway: 1) the binding of ligand to receptors, in which a very high ligand level may cause receptor saturation; and 2) CheY-P controlled motor state, which is extremely discrete and stochastic.
Mass action rates are also extremely reliable for stochastic modeling simulations.
We agree that stochastic variability is extremely important our revised Materials and methods section hopefully do a better job of communicating the details behind our stochastic model.
Further, since technical and stochastic variation are extremely unlikely to result in better correlation between mRNA and protein expression measurements, we argue that the technology resulting in better correlation must provide more accurate measurements.
The related known results also show us that finding the threshold value for the stochastic epidemic systems is extremely difficult and exciting; see, for example, [6 10].
The discordant detection of five cases is therefore most likely a result of stochastic PCR variability on extremely low concentrations of methylated DNA in the respective plasma samples.
This method is both extremely accurate at finding the mean and fully stochastic, that is each simulation gives a different stochastic realisation and the full probability density can be found from a histogram of many simulations.
However, the computational cost for that kind of stochastic simulations can also be extremely high.
This is especially important with extremely low quantities of input RNA where stochastic effects due to template dilution may be present.
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Justyna Jupowicz-Kozak
CEO of Professional Science Editing for Scientists @ prosciediting.com