Simulating ATO Mechanism and EGFR Signaling with Fuzzy Logic and Petri Net

Background: Interactions of many key proteins or genes in signalling pathway have been studied qualitatively in the literature, but only little quantitative information is available. Objective: Although much has been done to clarify the biochemistry of transcriptional dynamics in signalling pathway, it remains difficult to find out and predict quantitative responses. The aim of this study is to construct a computational model of epidermal growth factor receptor (EGFR) signalling pathway as one of hallmarks of cancer so as to predict quantitative responses. Material and Methods: In this analytical study, we presented a computational model to investigate EGFR signalling pathway. Interaction of Arsenic trioxide (ATO) with EGFR signalling pathway factors has been elicited by systematic search in data bases, as ATO is one of the mysterious chemotherapy agents that control EGFR expression in cancer. ATO has dichotomous manner in vivo, dependent on its concentration. According to fuzzy rules based upon qualitative knowledge and Petri Net, we can construct a quantitative model to describe ATO mechanism in EGFR signalling pathway. Results: By Fuzzy Logic models that have the potential to trade with the loss of quantitative information on how different species interact, along with Petri net quantitatively describe the dynamics of EGFR signalling pathway. By this model the dynamic of different factors in EGFR signalling pathway is achieved. Conclusion: The use of Fuzzy Logic and PNs in biological network modelling causes a deeper understanding and comprehensive analysis of the biological networks.

Keywords:

Arsenic trioxide , EGFR , Fuzzy Logic model , Petri net , Signalling pathway , Logic , Algorithms , Theoretical