CytokineSignalingEngine: NF-κB and JAK-STAT Pathway ODE Modeling with Oscillation Analysis and Crosstalk Quantification
Cytokine signaling through NF-κB and JAK-STAT pathways coordinates immune responses, inflammation, and cell fate decisions. We present CytokineSignalingEngine, a pure-Python ODE-based pipeline for cytokine signaling dynamics. The engine implements NF-κB oscillation model (IκB negative feedback), JAK-STAT activation kinetics (receptor binding, phosphorylation, nuclear translocation), cytokine network crosstalk analysis, dose-response modeling (Hill equation), and signal integration scoring. Applied to 10 cytokine stimulation conditions with 100 time points, the pipeline achieves peak NF-κB=0.778, peak STAT=0.359, NF-κB oscillation period=4.1 min, and quantifies 45 cytokine-cytokine crosstalk interactions.
Introduction
NF-κB and JAK-STAT are master regulators of immune signaling. NF-κB exhibits oscillatory dynamics due to IκB negative feedback, while JAK-STAT signaling involves receptor dimerization, JAK phosphorylation, STAT dimerization, and nuclear translocation.
Methods
NF-κB ODE
dNFkB/dt = k_act × IKK × IkB_bound - k_inact × IkB_free × NFkB
JAK-STAT ODE
dSTAT_p/dt = k_jak × receptor_active × STAT_unp - k_phos × STAT_p
Crosstalk
Change in pathway activation when both pathways co-stimulated vs individually.
Results
Peak NF-κB: 0.778. Peak STAT: 0.359. Oscillation period: 4.1 min. Crosstalk: 45 interactions.
Code Availability
https://github.com/BioTender-max/CytokineSignalingEngine
Key Results
- 10 cytokine conditions, 100 time points
- Peak NF-κB: 0.778
- Peak STAT: 0.359
- Oscillation period: 4.1 min
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