Stochastic estimation of fluxes in metabolic networks
Description
The qualitative and quantitative information conveyed by metabolic networks are important for
regulating the metabolism of an organism to achieve desired targets. One approach to quantification
is the 13C
tracer experiment which aims to provide information on metabolic fluxes. The flux
estimation problem is addressed in steady state and dynamic conditions in this presentation. The
problem formulation in the steady state leads to a latent variable model structure which is utilised in
applying the stochastic estimation framework to solve the flux quantification problem. A natural
algorithm to solve this problem is the expectationmaximisation
algorithm which is applied first.
This is extended to the Markov Chain Monte Carlo algorithm to account for nonGaussian
measurement noise. Finally, a sequential Monte Carlo filter is used to determine the fluxes under
dynamic conditions. Results are presented for the central metabolism of Cornybacterium
Glutamicum in the steady state and using a simulated metabolic network for the dynamic case.
| Slides | |
| 0:00 | Stochastic Estimation of Fluxes in Metabolic Networks |
| 0:26 | Overview |
| 1:39 | Systems Biology |
| 1:57 | Metabolic Systems |
| 3:13 | Metabolic Network Map of E.coli[2] |
| 4:04 | Metabolic Network Analysis |
| 5:55 | Metabolic Flux Analysis |
| 8:17 | Stoichiometric Equation |
| 8:52 | Flux Balance Analysis |
| 10:44 | 13C Tracer based Flux Analysis |
| 13:29 | MFA based on 13C Tracer Experiment |
| 16:40 | Metabolic Flux Estimation |
| 18:28 | Total Least Squares Estimation |
| 18:32 | Metabolic Flux Estimation |
| 19:07 | Total Least Squares Estimation |
| 19:38 | Cyclic Pentose Phosphate Pathwayand its 13C Enrichment Balance |
| 20:35 | Least Squares Flux Estimates |
| 21:14 | Linear least squares performance |
| 22:02 | Total Least Squares Estimation |
| 22:23 | Nonlinear Least Squares Estimation |
| 22:49 | Incomplete Data and Noise |
| 24:25 | Maximum Likelihood Estimation |
| 24:42 | Expectation Maximisation |
| 24:55 | Incomplete Data and Noise |
| 25:07 | Maximum Likelihood Estimation |
| 25:09 | Expectation Maximisation |
| 25:29 | Expectation Conditional Maximisation |
| 26:10 | Metabolic Flux Estimation by ECM |
| 27:00 | Central metabolism of Corynebacterium glutamicum |
| 27:15 | ECM Estimation Results |
| 28:53 | Central metabolism of Corynebacterium glutamicum |
| 29:07 | ECM Estimation Results |
| 29:09 | ECM Algorithm Efficiency |
| 29:27 | Incorporating Noise |
| 29:37 | Bayesian Approach |
| 29:46 | Incorporating Noise |
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