MCB111: Mathematics in Biology (Fall 2020)
week 10:
Molecular Population Dynamics as a Markov Process
Stochastic simulation of transcriptional bursting
Sampling fast from an exponential distribution
In the Gillespie algorithm, dwell times \(\tau\) follow a exponential distribution.
The probability density function (PDF) is
\[PDF(t) = W_R e^{W_R\ t}.\]In order to sample a dwell time \(\tau\), we used the cumulative probability function (CDF)
\[CDF(\tau) = \int_0^{\tau} W_R\ e^{W_R\ t}\ dt\]such that for a random number \(0\leq x\leq 1\), the sampled dwell \(\tau\) time is given by
\[x = CDF(\tau).\]The CDF of the exponential distribution has a closed form given by
\[CDF(\tau) = \int_0^{\tau} W_R\ e^{W_R\ t} = 1  e^{W_R\ \tau}.\]Then, the sampled time is given by
\[\tau = \frac{1}{W_R}\ \log(1x).\]If \(x\) is a random number in \([0,1]\), then \(1x\) is also a random number in the same range, then we can take the sampled dwell time \(\tau\) given by
\[\tau = \frac{1}{W_R}\ \log(x).\]Implementing the Gillespie algorithm
For the stochastic process described in Figure 1, the reactions are given by
Figure 1. Regulation of a single gene, transcription and translation, as well as RNA and Protein degradation processes.
r  reaction  propensity \(w_r\)  \(\eta(R)\)  \(\eta(P)\) 

1  \(\mbox{Gene(I)} \overset{k_b}{\longrightarrow} \mbox{Gene(A)}\)  \(k_b\)  \(0\)  \(0\) 
2  \(\mbox{Gene(A)} \overset{k_u}{\longrightarrow} \mbox{Gene(I)}\)  \(k_u\)  \(0\)  \(0\) 
3  \(\mbox{Gene(A)} \overset{k_1}{\longrightarrow} RNA\)  \(k_1\)  \(+1\)  \(0\) 
4  \(RNA \overset{k_2}{\longrightarrow} \emptyset\)  \(k_2 R\)  \(1\)  \(0\) 
5  \(RNA \overset{k_3}{\longrightarrow} Protein\)  \(k_3 R\)  \(0\)  \(+1\) 
6  \(Protein \overset{k_4}{\longrightarrow} \emptyset\)  \(k_4 P\)  \(0\)  \(1\) 
Then the Gillespie algorithm works as follows

Initialize at \(t = 0\),
\[\begin{aligned} Gact &= 1,\\ R &= 0,\\ P &= 0.\\ \end{aligned}\] 
Keep a current count of \(t\), \(Gact\), \(R\) and \(P\).
 \(Gact = 1\) if the gene is active (A) at time \(t\), or
 \(Gact = 0\) if the gene is inactive (I) at time \(t\).
 \(R\) is the number of RNA molecules at time \(t\).
 \(P\) is the number of protein molecules at time \(t\).

Sample a dwell time \(\tau\) from a exponential distribution
\[W_R\ e^{W_R\ t},\]where the total propensity is given by
\[\begin{aligned} W_R = w_1 + w_4 + w_5 + w_6,\quad &\mbox{if}\, Gact = 0,\\ W_R = w_2 + w_3 + w_4 + w_5 + w_6,\quad &\mbox{if}\, Gact = 1.\\ \end {aligned}\] 
Update the current time \(t\) as

Sample one reaction \(r\) according to their propensities
\[P(r) = \frac{w_r}{W_R}.\] 
Update \(Gact\), \(R\) and \(P\)

If \(r = 1\), then \(Gact=0 \rightarrow 1\)

If \(r = 2\), then \(Gact=1 \rightarrow 0\)

If \(r = 3\), then \(R \rightarrow R+1\)

If \(r = 4\), then \(R \rightarrow R1\)

If \(r = 5\), then \(P \rightarrow P+1\)

If \(r = 6\), then \(P \rightarrow P1\)


Update the propensities according to the new values of \(Gact\), \(R\) and \(P\).

Go back to sampling a new dwell time, until a maximum time \(T\).