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  4. Integrating omics data into metabolic models of lipids: a platform for the identification of gene mutations from lipidomics data
 
conference presentation

Integrating omics data into metabolic models of lipids: a platform for the identification of gene mutations from lipidomics data

Savoglidis, Georgios  
•
Angelino, Paolo  
•
Riezman, Howard
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2013
2013 AIChE Annual Meeting

Kinetic models of metabolic networks are mapping the biochemical reactions taking part in a cell to a mathematical representation. They are the blueprints of the biochemical network, connecting enzymatic activities and metabolic compounds. Kinetic models have been used in systems biology to produce estimates of response of an organism to stress and to reveal potentially efficient targets for cellular engineering. Lipids are major constituents of the cell membrane. They are responsible for major properties of the cellular membranes: hydrophobicity, selective permeability and being the scaffold of signaling proteins. Many diseases are associated with alterations in the lipid distribution in the cell and the composition of membrane domains. Metabolic syndrome, obesity, atherosclerosis, as well as Alzheimer’s, Huntington’s diseases and cancer, all originate from alterations in some stage of lipid biosynthesis. Therefore, advancement of knowledge in the field of lipid metabolism will provide novel insights for further biomedical research and potential strategies for drug development. In the current study we combine lipidomics data and metabolic models of lipid metabolism in yeast Saccharomyces cerevisiae. We use the models as platform for the application of sensitivity analysis and metabolic control analysis, which involves direct and inverse sensitivity analysis. In direct sensitivity analysis we quantify how the changes in enzymatic activities, either by gene deletion or RNAi, are mapped through the metabolic pathway model into variations in lipid profiles. This analysis allows us to identify the effects of the perturbations in enzyme activities (inhibition or overexpression) on the distribution of the lipids synthesized as the end products of the network. We further extend the analysis by casting the inverse problem. With the inverse sensitivity analysis framework, we consider as input an altered lipidomic profile and we are able to identify, the responsible perturbations in enzyme activities that account for such a change. The results of the analysis have been confirmed based on lipidomics analysis of mutant yeast cells. Although we demonstrate the application of the method in models of lipid metabolism it is possible to be applied to biochemical systems of various parts of metabolism and sizes creating a modular platform for identification of mutations.

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Type
conference presentation
Author(s)
Savoglidis, Georgios  
Angelino, Paolo  
Riezman, Howard
Hatzimanikatis, Vassily  
Date Issued

2013

Written at

EPFL

EPFL units
LCSB  
Event nameEvent placeEvent date
2013 AIChE Annual Meeting

San Fransisco, California, USA

November 3-8, 2013

Available on Infoscience
October 31, 2014
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/108112
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