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Polymerase Chain Reaction: A Markov Process Approach. Mikhail V. Velikanov et al. J. theor. Biol. 1999 Summarized by 임희웅 2003.8.12. Contents. Introduction Markov Process Model for Primer Extension Model for Multi-Cycle PCR Runs Numerical Results Discussion. Introduction. - PowerPoint PPT Presentation
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Polymerase Chain Reaction:A Markov Process Approach
Mikhail V. Velikanov et al.
J. theor. Biol. 1999
Summarized by 임희웅2003.8.12
Contents Introduction Markov Process Model for Primer
Extension Model for Multi-Cycle PCR Runs Numerical Results Discussion
Introduction A stochastic approach to PCR
Focus on the microscopic nature of amplification process Elementary reaction: binding of dNTP Markov process master equation
Analytical solution for the probability distribution of DNA length
Main qualitative feature Sensitivity of the reaction condition The amplification plateau effect Optimal duration of amplification for each cycle
Markov Process Model for Primer Extension Amplification process as Markov process
Binding of dNTP occurs randomly, with the probability per unit time determined entirely by the present state of the system.
State: length of primer Reaction rate: w = k(t) n
n: total number of dNTP in the current system k(t): the rate coefficient which depends on temperature (time) l + n = l0 + n0 = m0 constant
n0: initial total number of dNTP
l0 l l+1… L…
Master Equation The master equation for the primer
extension process
Analytical Solution
Model for Multi-Cycle PCR Runs Additional feature
Increasing number of DNA molecules Statistical independence of the extension process n0: initial number of dNTPs per template strand
np: the number of primers per template strand
Complementarity Two kinds of strand: +, - Pi
+(l,n): Prob. distribution of + strand in ith cycle
Evolution of Probability Distribution
ηn: duration of the extension phase of each cycle
The distribution for the first cycle Consumed dNTP in first cycle
Numerical Result Simulation for PCR Runs
Optimization of PCR Runs
Arrhenius’ law
Discussion Primary assumption
DNA synthesis occurs independently on each template strand.
Advantage in Markov process approach The model can be solved exactly by analytical means.
simple calculation It accounts for the fluctuations inherent in PCR kinetics
through a description of their natural microscopic source. The model is easy to modify and can be used as the basis
for constructing dedicated algorithms for numerical simulations of PCR.