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The Application Of MCMC Method Based On Approximate Likelihood In RNA Interference Model

Posted on:2020-01-08Degree:MasterType:Thesis
Country:ChinaCandidate:T L MaFull Text:PDF
GTID:2430330626963975Subject:Computer Science and Technology
Abstract/Summary:PDF Full Text Request
RNA interference is a post-transcriptional gene silencing phenomenon induced by double-stranded RNA,and it is commonly found in organisms.As an efficient and highly specific gene regulation technology,RNA interference has a wide range of applications.In many applications,a quantitative model of RNA interference that can describe the relationship between the siRNA dose and RNA interference effect should be needed as theoretical support.However,there are not many studies on quantitative models of RNA interference.Based on previous research,this article has made a more in-depth exploration.The main content is three points:1.Combining the degradation delay and the transportation delay of mRNA during the RNA interference process,a delay differential equation model of RNA interference is obtained.Then,a detailed qualitative analysis and parameter sensitivity analysis of the model is made;2.The method for solving the siRNA dose optimization problem is given according to the optimization control theory;3.For the RNA interference model,parameter inference problem with sparse and noisy experimental data proposed,an MCMC method based on approximate likelihood is presented.The research results show that the introduction of the time delay will affect the stability of the only positive equilibrium point of the RNA interference model.With the increase of time delay,the equilibrium point will be destabilized by the Hopf bifurcation,and the limit cycle will appear at the Hopf bifurcation.Besides,comparing the optimized control results of the time-lag model and the time-lag-free model,we found that the optimal siRNA dose under the time-lag model is less than the dose under the time-lag model,and its RNA interference effect is also better than that without the time-lag model.Finally,we discuss the advantages and disadvantages of the proposed approximate likelihood methods and propose to use approximate likelihood methods based on approximate Bayesian inference algorithms with uniform or Gaussian kernels.In this paper,in the field of RNA interference application,the dynamic behavior of RNA interference quantitative model and its parameter inference methods are studied.The research content of RNA interference is expanded,which has certain guiding significance for the future application and research of RNA interference.
Keywords/Search Tags:RNA interference, Approximate Bayesian Computation, Markov chain Monte Carlo Method, Delay, Oscillation period, Sensitivity analyse, Optimal control
PDF Full Text Request
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