LAPSE:2018.0430
Published Article
LAPSE:2018.0430
A Cybernetic Approach to Modeling Lipid Metabolism in Mammalian Cells
Lina Aboulmouna, Shakti Gupta, Mano R. Maurya, Frank T. DeVilbiss, Shankar Subramaniam, Doraiswami Ramkrishna
August 28, 2018
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.
Keywords
cybernetic modeling, lipids, metabolic objective functions, omics data, Optimization, prostaglandin metabolism
Suggested Citation
Aboulmouna L, Gupta S, Maurya MR, DeVilbiss FT, Subramaniam S, Ramkrishna D. A Cybernetic Approach to Modeling Lipid Metabolism in Mammalian Cells. (2018). LAPSE:2018.0430
Author Affiliations
Aboulmouna L: The Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA
Gupta S: Department of Bioengineering and San Diego Supercomputer Center, University of California San Diego, La Jolla, CA 92093, USA [ORCID]
Maurya MR: Department of Bioengineering and San Diego Supercomputer Center, University of California San Diego, La Jolla, CA 92093, USA
DeVilbiss FT: The Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA
Subramaniam S: Department of Bioengineering and San Diego Supercomputer Center, University of California San Diego, La Jolla, CA 92093, USA; Departments of Computer Science and Engineering, Cellular and Molecular Medicine, and the Graduate Program in Bioinformatics, Uni
Ramkrishna D: The Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN 47907, USA
[Login] to see author email addresses.
Journal Name
Processes
Volume
6
Issue
8
Article Number
E126
Year
2018
Publication Date
2018-08-12
Published Version
ISSN
2227-9717
Version Comments
Original Submission
Other Meta
PII: pr6080126, Publication Type: Journal Article
Record Map
Published Article

LAPSE:2018.0430
This Record
External Link

doi:10.3390/pr6080126
Publisher Version
Download
Files
[Download 1v1.pdf] (1.4 MB)
Aug 28, 2018
Main Article
License
CC BY 4.0
Meta
Record Statistics
Record Views
809
Version History
[v1] (Original Submission)
Aug 28, 2018
 
Verified by curator on
Aug 28, 2018
This Version Number
v1
Citations
Most Recent
This Version
URL Here
https://psecommunity.org/LAPSE:2018.0430
 
Original Submitter
Auto Uploader for LAPSE
Links to Related Works
Directly Related to This Work
Publisher Version