Exploiting Hybrid Functional Petri Nets to Investigate Transcriptional Activity of Hemoglobin Switching

β-thalassemia, SCD and other human β-globin gene related diseases are the major sources of mortality in the world. Bone marrow transplantation, gene therapy and supporting care with transfusion of red blood cells are possible treatments of human β-globin gene related diseases. However, none of these treatments has progressed to the level of worldwide efficient clinical therapy. Reactivation of γ-globin gene in affected adults is known to be an efficient measure to ameliorate the severity of β-thalassemia and SCD. In this study, we propose new strategies for β-globin disorders. These approaches are centered upon induction of γ-globin gene expression. We use Cell Illustrator software tool to create HFPN model of hemoglobin switching network, validate the model with available qPCR data and perform simulations to compare the efficiency of the proposed strategies with the existing drug and RNAi-mediated therapies. Simulation results show that our drug and RNAi-mediated strategies have been postulated to lead to the potential induction of γ-globin gene expression. Keywords: Quantitative modeling, hybrid functional Petri net, β-thalassemia, hemoglobin switching network