Finding intervention points in the pathogenesis of Dengue viral infection.
We use probabilistic Boolean networks to simulate the pathogenesis of Dengue Hemorraghic Fever (DHF). Based on Chaturvedi's work, the strength of cytokine influences are modeled stochastically as inducement probabilities. We use an aggregated function approach to derive the DHF Infection Model. Two basins of attractors are observed with synchronous updating; the Null Infection cycle attractor shows an expected cross-regulation of Th1 and Th2 cytokines corresponding to the homeostasis of an uninfected person, while the DHF Infection attractor shows the onset of DHF. With asynchronous updating, our model remains valid with clinical comparisons against qualitative changes in signal durations. In order to find intervention points that could prevent DHF we design a genetic algorithm to shift the DHF attractor to the DF attractor basin by using the DF final state as the fitness measure. Our simulation results identify TGF-beta, IL-8 and IL-13 as the intervention points which are consistent with known clinical results to prevent DHF from occurring.
Tay
Joc C
JC
Evolutionary & Complex Systems Programme, Nanyang Technological University, Singapore. asjctay@ntu.edu.sg
Tan
Philip
P
D000465:Algorithms; D003716:Dengue Virus / Q000378:metabolism*; D004196:Disease Outbreaks; D005786:Gene Expression Regulation; D006801:Humans; D018793:Interleukin-13 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008954:Models, Biological; D015233:Models, Statistical; D008962:Models, Theoretical; D011336:Probability; D011381:Programming Languages; D019595:Severe Dengue / Q000175:diagnosis* / Q000628:therapy*; D013269:Stochastic Processes; D016212:Transforming Growth Factor beta / Q000378:metabolism
D018793:Interleukin-13; D016209:Interleukin-8; D016212:Transforming Growth Factor beta