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Processes 2018, 6(8), 126; https://doi.org/10.3390/pr6080126

A Cybernetic Approach to Modeling Lipid Metabolism in Mammalian Cells

1
The Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA
2
Department of Bioengineering and San Diego Supercomputer Center, University of California San Diego, La Jolla, CA 92093, USA
3
Departments of Computer Science and Engineering, Cellular and Molecular Medicine, and the Graduate Program in Bioinformatics, University of California San Diego, La Jolla, CA 92093, USA
*
Authors to whom correspondence should be addressed.
Received: 16 July 2018 / Revised: 3 August 2018 / Accepted: 7 August 2018 / Published: 12 August 2018
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Abstract

The goal-oriented control policies of cybernetic models have been used to predict metabolic phenomena such as the behavior of gene knockout strains, complex substrate uptake patterns, and dynamic metabolic flux distributions. Cybernetic theory builds on the principle that metabolic regulation is driven towards attaining goals that correspond to an organism’s survival or displaying a specific phenotype in response to a stimulus. Here, we have modeled the prostaglandin (PG) metabolism in mouse bone marrow derived macrophage (BMDM) cells stimulated by Kdo2-Lipid A (KLA) and adenosine triphosphate (ATP), using cybernetic control variables. Prostaglandins are a well characterized set of inflammatory lipids derived from arachidonic acid. The transcriptomic and lipidomic data for prostaglandin biosynthesis and conversion were obtained from the LIPID MAPS database. The model parameters were estimated using a two-step hybrid optimization approach. A genetic algorithm was used to determine the population of near optimal parameter values, and a generalized constrained non-linear optimization employing a gradient search method was used to further refine the parameters. We validated our model by predicting an independent data set, the prostaglandin response of KLA primed ATP stimulated BMDM cells. We show that the cybernetic model captures the complex regulation of PG metabolism and provides a reliable description of PG formation. View Full-Text
Keywords: lipids; prostaglandin metabolism; omics data; cybernetic modeling; optimization; metabolic objective functions lipids; prostaglandin metabolism; omics data; cybernetic modeling; optimization; metabolic objective functions
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Aboulmouna, L.; Gupta, S.; Maurya, M.R.; DeVilbiss, F.T.; Subramaniam, S.; Ramkrishna, D. A Cybernetic Approach to Modeling Lipid Metabolism in Mammalian Cells. Processes 2018, 6, 126.

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