Automatic construction of Petri net models for computational simulations of molecular interaction network.

Petri nets are commonly applied in modeling biological systems. However, construction of a Petri net model for complex biological systems is often time consuming, and requires expertise in the research area, limiting their application. To address this challenge, we developed GINtoSPN, an R package that automates the conversion of multi-omics molecular interaction network extracted from the Global Integrative Network (GIN) into Petri nets in GraphML format. These GraphML files can be directly used for Signaling Petri Net (SPN) simulation. To demonstrate the utility of this tool, we built a Petri net model for neurofibromatosis type I. Simulation of NF1 gene knockout, compared to normal skin fibroblast cells, revealed persistent accumulation of Ras-GTPs as expected. Additionally, we identified several other genes substantially affected by the loss of NF1's function, exhibiting individual-specific variability. These results highlight the effectiveness of GINtoSPN in streamlining the modeling and simulation of complex biological systems.