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Parameter Estimation in Systems Biology

Bayesian Inference for Systems Biological Models via a Diffusion Approximation

author: Andrew Golightly, University of Newcastle

Description

As post-genomic biology becomes more predictive, the ability to infer rate parameters (known as reverse-engineering) of biochemical networks will become increasingly important. One approach is to replace the underlying model by a diffusion approximation and the model is identified using discrete-time (and often incomplete) data that is subject to error. Unfortunately, likelihood based inference can be problematic as closed form transition densities of nonlinear diffusions are rarely available. A widely used solution involves the introduction of latent data points between every pair of observations to allow an Euler-Maruyama approximation of the true transition densities to become accurate. Markov chain Monte Carlo (MCMC) methods can then be used to sample the posterior distribution of latent data and model parameters; however, naive schemes suffer from a mixing problem that worsens with the degree of augmentation. A reparameterisation is therefore implemented to overcome this difficulty and the methodology is applied to a simple prokaryotic auto-regulatory gene network.

Joint work with Darren J. Wilkinson

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Slides
0:01 Bayesian Inference for Systems Biology Models via a Diffusion Approximation
1:06 Overview
1:54 Computational Systems Biology (CSB)
2:38 Modelling
3:37 Mass Action Kinetics
4:43 Mass Action Kinetics (2)
5:58 Markov Process Models
7:50 The Gillespie algorithm
9:02 Example: Lotka-Volterra
10:07 The Lotka-Volterra model
10:24 The Lotka-Volterra model
10:38 The Lotka-Volterra model
10:46 The Lotka-Volterra model
10:53 The Lotka-Volterra model
11:05 The Lotka-Volterra model
11:47 Key differences
12:19 Fully Bayesian inference
13:58 The Stochastic-Kinetic Diffusion Approximation
15:19 Inference for Diffusions
16:22 Bayesian Imputation approach
18:06 Gibbs Sampling
20:21 Irreducible Global MCMC Schemes
22:40 Modified Innovation Scheme
23:31 Algorithm
24:43 Acceptance probabilities
25:41 Toy Application: Prokaryotic Auto-Regulation
27:17 Simulation Study
28:11 Results, m = 10, Gibbs Sampler
28:43 Results, m = 10, Innovation Scheme
29:01 Results, m = 10, Innovation Scheme
29:14 Results, m = 10, Innovation Scheme
29:29 Results, m = 10, Innovation Scheme
29:48 Results, m = 10, Innovation Scheme
30:26 Summary
31:10 Contact details...

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