A Modular Model of the Apoptosis Machinery
Using a modular principle of computer hardware as a metaphor, we defined and implemented in the BioUML platform a module concept for biological pathways. BioUML provides a user interface to create modular models and convert them automatically into plain models for further simulations. Using this approach, we created the apoptosis model including 13 modules: death stimuli (TRAIL, CD95L, and TNF-α)-induced activation of caspase-8; survival stimuli (p53, EGF, and NF-κB) regulation; the mitochondria level; cytochrome C- and Smac-induced activation of caspase-3; direct activation of effector caspases by caspase-8 and − 12; PARP and apoptosis execution phase modules. Each module is based on earlier published models and extended by data from the Reactome and TRANSPATH databases. The model ability to simulate the apoptosis-related processes was checked; the modules were validated using experimental data. Availability: http://www.biouml.org/apoptosis.shtml.
KeywordsOutput Port Type Rule Diagram Type Substitution Rule Modular Model
- 3.Hamada H, Tashima Y, Kisaka Y, Iwamoto K, Hanai T, Eguchi Y, Okamoto M (2008) Sophisticated framework between cell cycle arrest and apoptosis induction based on p53 dynamics. PLoS One 4(3):e4795:1–7Google Scholar
- 5.Legewie S, Bluthgen N, Herzel H (2006) Mathematical modeling identifies inhibitors of apoptosis as mediators of positive feedback and bistability. PLoS Comput Biol 2(9):e120:1061–1073Google Scholar
- 18.Farfan A, Yeager T, Moravec R, Niles A (2004) Multiplexing homogeneous cell-based assays. Cell Notes 10:15–18Google Scholar