RT Journal
A1 Cho, Kwang-Hyun
A1 Shin, Sung-Young
A1 Lee, Hyeon-Woo
A1 Wolkenhauer, Olaf
T1 Investigations Into the Analysis and Modeling of the TNFα-Mediated NF-κB-Signaling Pathway
JF Genome Research 
JO Genome Research 
YR 2003 
FD November 01 
VO 13 
IS 11 
SP 2413 
OP 2422 
DO 10.1101/gr.1195703 
UL http://genome.cshlp.org/content/13/11/2413.abstract 
AB In this study, we propose a system-theoretic approach to the analysis and quantitative modeling of the TNFα-mediated NF-κB-signaling pathway. Tumor necrosis factor α (TNFα) is a potent proinflammatory cytokine that plays an important role in immunity and inflammation, in the control of cell proliferation, differentiation, and apoptosis. To date, there have been numerous approaches to model cellular dynamics. The most prominent uses ordinary differential equations (ODEs) to describe biochemical reactions. This approach can provide us with mathematically well-founded and tractable interpretations regarding pathways, especially those best described by enzyme reactions. This work first introduces a graphical method to intuitively represent the TNFα-mediated NF-κB-signaling pathway and then utilizes ODEs to quantitatively model the pathway. The simulation study shows qualitative validation of the proposed model compared with experimental results for this pathway. The proposed system-theoretic approach is expected to be further applicable to predict the signaling behavior of NF-κB in a quantitative manner for any variation of the ligand, TNFα.