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Probabilistic Modelling of Networks and Pathways

Stochastic estimation of fluxes in metabolic networks

author: Visakan Kadirkamanathan, Department of Molecular Biology and Biotechnology, University of Sheffield

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.

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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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