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  4. iSCHRUNK – in Silico Approach to Characterization and Reduction of Uncertainty in the Kinetic Models of Genome-scale Metabolic Networks
 
conference poster not in proceedings

iSCHRUNK – in Silico Approach to Characterization and Reduction of Uncertainty in the Kinetic Models of Genome-scale Metabolic Networks

Andreozzi, Stefano  
•
Miskovic, Ljubisa  
•
Hatzimanikatis, Vassily  
2015
Biochemical and Molecular Engineering XIX

Accurate determination of physiological states of cellular metabolism requires detailed information about metabolic fluxes, metabolite concentrations and distribution of enzyme states. Integration of fluxomics and metabolomics data, and thermodynamics-based metabolic flux analysis contribute to improved understanding of steady-state properties of metabolism. However, knowledge about kinetics and enzyme activities though essential for quantitative understanding of metabolic dynamics remains scarce and involves uncertainty. Here, we present a novel computational methodology that allow us to determine and quantify the kinetic parameters that correspond to a certain physiology as it is described by a given metabolic flux profile and a given metabolite concentration vector. Though we initially determine kinetic parameters that involve a high degree of uncertainty, through the use of kinetic modeling and machine learning principles we are able to obtain more accurate ranges of kinetic parameters, and hence we are able to reduce the uncertainty in the model analysis. We computed the distribution of kinetic parameters for glucose-fed E. coli producing 1,4-butanediol and we discovered that the observed physiological state corresponds to a narrow range of kinetic parameters of only a few enzymes, whereas the kinetic parameters of other enzymes can vary widely. Furthermore, this analysis suggests which are the enzymes that should be manipulated in order to engineer the reference state of the cell in a desired way. The proposed approach also sets up the foundations of a novel type of approaches for efficient, non-asymptotic, uniform sampling of solution spaces.

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Type
conference poster not in proceedings
Author(s)
Andreozzi, Stefano  
Miskovic, Ljubisa  
Hatzimanikatis, Vassily  
Date Issued

2015

Subjects

kinetic models

•

uncertainty

•

machine learning

•

metabolic engineering

•

synthetic biology

•

systems biology

Written at

EPFL

EPFL units
LCSB  
Event nameEvent placeEvent date
Biochemical and Molecular Engineering XIX

Puerto Vallarta, Mexico

July 12-16, 2015

Available on Infoscience
September 3, 2015
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/117575
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