Petri nets for the analysis of disease maps: applied to the TNFR1 signaling pathway

Ina Koch
2021 Zenodo  
The talk introduces Petri net (PN) basics and discusses their application to modeling signaling pathways. We explain our wok on the TNFR1 signaling pathway focusing on different outcomes for the cell, its survival, apoptosis and necroptosis. We applied the PN formalism and invariant-based analysis. Based on experimental findings in the current literature, we constructed a PN model in terms of detailed molecular reactions for the molecular players, protein complexes, post-translational
more » ... slational modifications, and cross talks. 279 manatee invariants resulted from the PN model represent the combinatorial diversity of complete functional pathways, describing signal flows from receptor activation to the cellular responses. The largest fraction of 120 pathways steers the cell to survival, whereas 58 and 35 pathways lead to apoptosis and necroptosis, respectively. For 65 pathways, the triggered response is not deterministic, leading to multiple possible outcomes. Based on the PN model, we investigated the detailed knockout behavior and identified important checkpoints of the TNFR1 signaling pathway in terms of ubiquitination within complex I and the gene expression dependent on NF-κB, which controls the caspase activity in complex II and apoptosis induction.
doi:10.5281/zenodo.4462577 fatcat:mbwnhrzu5jfx3cmsbxaki4xga4