Systems Biology Approach for Mapping TNF -NF B Mathematical Model to a Protein Interaction Map

We investigated different mathematical models concerning signaling pathways and built a new pathway model for TNF -NF B signaling using an integrative analytical approach. This integrative approach consists of a knowledgebase, model designing/visualization and simulation environments. In particular, our new TNF -NF B 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 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 TNF NF B signaling and further increases the understanding of TNF -NF B signaling pathway. This tool can be downloaded through the following link (http://sourceforge.net/projects/dmsp11/).