Boolean Model of Yeast Apoptosis

Abstract

Programmed cell death (apoptosis) is mediated through various pathways based on different stimuli and like most biological processes it is a result of sequential activation/inhibition signals acting as input to downstream components. In the simplest possible way this input/output feature of any cellular process like apoptosis can be represented by a discrete model called Boolean model in which the state of one node, can be a gene or a cellular function, is determined by all inputs to that node. Based on extensive literature study we have developed a yeast apoptosis network. By converting a schematic network into the Boolean model several steady states were identified. Each steady state was tested with corresponding stimuli which was expected to activate the associated pathway. Less complex genetic network and conservation of apoptotic mechanisms among eukaryotes provide the possibility of including genes from different organisms into yeast apoptotic network. Based on these facts we selected three crucial players of human apoptotic pathway and insert them into the pre-existing yeast apoptotic network. Such "humanized yeast" (which can also be created experimentally) demonstrates model functionality according to experimental data. the other, expected, outcome of our model is the estimate of quantitative effect of each node in the network which is achieved by dynamic simulation from steady states of the network. Steady state predicted by both discrete and continues models are in agreement in all responses, except in response to osmotic shock as stimuli. Further investigation of the system behavior showed different levels of concentration for HOG1 gene, is experimentally well known for its activity in response to osmotic shock. Change in concentration of this specific gene in model confirms the experimentally stimulated cell follows, which proofs the accuracy of model prediction.