Trares2022 - Canonical NF-kB pathway, Petri net

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  • The canonical and non-canonical NF-κB pathways and their crosstalk: A comparative study based on Petri nets.
  • Trares K, Ackermann J, Koch I
  • Bio Systems , 1/ 2022 , Volume 211 , pages: 104564 , PubMed ID: 34688841
  • Network Aging Research, Heidelberg University, Bergheimer Straße 20, 69115, Heidelberg, Germany; Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany. Johann Wolfgang Goethe-University Frankfurt am Main, Faculty of Computer Science and Mathematics, Institute of Computer Science, Dept. of Molecular Bioinformatics, Robert-Mayer-Straße 11-15, 60325, Frankfurt am Main, Germany.
  • NF-κB is a protein complex that occurs in almost all animal cell types. It regulates the cellular immune responses to stimuli in the nucleus. Dysregulation of NF-κB can cause severe diseases like chronic inflammation, autoimmune diseases or cancer. We modeled the two major pathways leading from the external cellular stimulation of the CD40 receptor to the nuclear translocation of NF-κB dimers, the canonical and non-canonical pathway. Based on literature data, we developed two Petri net models describing these pathways. In a third Petri net, we combined the two models, introducing crosstalk specific in CD40L-stimulated B cells. In terms of structural properties, we checked the Petri nets for their consistency and correctness. To explore differences and similarities, we compared structural properties and the simulation behavior of the models. The non-canonical NF-κB pathway exhibited a more diverse regulation than the canonical pathway. Applying in silico knockout analyses, we were able to quantify the relevance of individual biochemical processes. We predicted interrelationships, e.g., between the synthesis of the protein NF-κB-inducing kinase and the processing of the precursor protein p100. The activation of the transcription factors, p50-RelA and p52-RelB, was affected by most of the knockouts. The results of the in silico knockout were in accordance with experimental studies. The Petri net models provide a basis for further analyses and could be extended to include gene expression, additional pathways, molecular processes, and kinetic data.
Submitter of the first revision: Ann-Kathrin Otto
Submitter of this revision: Ann-Kathrin Otto
Modellers: Kira Trares
Others: Ann-Kathrin Otto

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Mathematical Modelling Ontology Petri net

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  • Model originally submitted by : Ann-Kathrin Otto
  • Submitted: Jul 21, 2022 1:37:03 PM
  • Last Modified: Jul 21, 2022 1:37:03 PM
  • Version: 1 public model Download this version
    • Submitted on: Jul 21, 2022 1:37:03 PM
    • Submitted by: Ann-Kathrin Otto
    • With comment: Import of Trares2022 - Canonical NF-kB pathway, Petri net