Integrative Approach for Combining TNFα-NFκB Mathematical Model to a Protein Interaction Connectivity Map

We have investigated different mathematical models for signaling pathways and built a new pathway model for TNFα-NFκB signaling using an integrative analytical approach. This integrative approach consists of a knowledgebase, model designing/visualization and simulation environments. In particular, our new TNFα-NFκB signaling pathway model was developed based on literature studies and the use of ordinary differential equations and a detailed protein-protein interaction connectivity map within this approach. Using the most detailed mathematical model as a base model, three new relevant proteins --- TRAF1, FLIP, and MEKK3 --- were identified and included in our new model. Our results show that this integrative approach offers the most detailed and consistent mathematical description for TNFα-NFκB signaling and further increases the understanding of TNFα-NFκB signaling pathway.