(710f) Cybernetic Modeling of the Inflammatory Response in Mouse Bone Marrow Derived Machrophage Cells

The goal-oriented control policies of cybernetic models have been used to predict metabolic phenomena ranging from complex substrate uptake patterns and dynamic metabolic flux distributions to the behavior of gene knockout strains. Cybernetic theory builds on the perspective that metabolic regulation is organized towards achieving goals relevant to an organism’s survival or displaying a specific phenotype in response to a stimulus. While cybernetic models have previously been established by prior work carried out in bacterial systems, we have shown that cybernetic modeling can be applied to complex biological systems with a predefined goal [1].

Here, we have modeled eicosanoid inflammatory mediators, the Prostaglandins (PG) and Leukotrienes (LT), in mouse bone marrow derived macrophage (BMDM) cells stimulated by Kdo2-Lipid A (KLA) and adenosine triphosphate (ATP) using cybernetic control variables. Transcriptomic and lipidomic data for eicosanoid biosynthesis and conversion was obtained from the LIPID MAPS database. We validated our model by predicting an independent data set, the response of KLA primed ATP stimulated BMDM cells. We show that the cybernetic model captures the complex regulation of eicosanoid metabolism and provides a reliable description of PG and LT formation.

References:

1. L. Aboulmouna; Gupta, S.; Maurya, M.R.; Subramaniam, S.; Ramkrishna, D. Processes, 6(8):126, 2018.

Acknowledgements:

This work is supported by the Center for Science of Information (CSoI), a National Science Foundation Science and Technology Center, under grant agreement CCF-0939370.