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Research output: Contribution in Book/Report/Proceedings - With ISBN/ISSN › Conference contribution/Paper › peer-review
Research output: Contribution in Book/Report/Proceedings - With ISBN/ISSN › Conference contribution/Paper › peer-review
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TY - GEN
T1 - Investigating IKK Dynamics in the NF-κB Signalling Pathway using X-Machines
AU - Williams, Richard Alun
AU - Timmis, Jon
AU - Qwarnstrom, Eva E.
PY - 2017/6/5
Y1 - 2017/6/5
N2 - The transcription factor NF-κB is a biological component that is central to the regulation of genes involved in the innate immune system. Dysregulation of the pathway is known to be involved in a large number of inflammatory diseases. Although considerable research has been performed since its discovery in 1986, we are still not in a position to control the signalling pathway, and thus limit the effects of NF-κB within promotion of inflammatory diseases. We have developed an agent-based model of the IL-1 stimulated NF-κB signalling pathway, which has been calibrated to wet-lab data at the single-cell level. Through rigorous software engineering, we believe our model provides an abstracted view of the underlying real-world system, and can be used in a predictive capacity through in silico experimentation. In this study, we have focused on the dynamics of the IKK complex and its activation of NF-κB. Our agent-based model suggests that the pathway is sensitive to: variations in the binding probability of IKK to the inhibited NF-κB-IκBα complex; and variations in the temporal rebinding delay of IKK.
AB - The transcription factor NF-κB is a biological component that is central to the regulation of genes involved in the innate immune system. Dysregulation of the pathway is known to be involved in a large number of inflammatory diseases. Although considerable research has been performed since its discovery in 1986, we are still not in a position to control the signalling pathway, and thus limit the effects of NF-κB within promotion of inflammatory diseases. We have developed an agent-based model of the IL-1 stimulated NF-κB signalling pathway, which has been calibrated to wet-lab data at the single-cell level. Through rigorous software engineering, we believe our model provides an abstracted view of the underlying real-world system, and can be used in a predictive capacity through in silico experimentation. In this study, we have focused on the dynamics of the IKK complex and its activation of NF-κB. Our agent-based model suggests that the pathway is sensitive to: variations in the binding probability of IKK to the inhibited NF-κB-IκBα complex; and variations in the temporal rebinding delay of IKK.
U2 - 10.1109/CEC.2017.7969320
DO - 10.1109/CEC.2017.7969320
M3 - Conference contribution/Paper
SN - 9781509046027
SP - 249
EP - 256
BT - Proceedings of the 2017 IEEE Congress on Evolutionary Computation
PB - IEEE
ER -