Modularisation of published and novel models toward a complex KIR2DL4 pathway in pbNK cell

KIR2DL4 is an interesting receptor expressed on the peripheral blood natural killer (pbNK) cell as it can be either activating or inhibitory depending on the amino acid residues in the domain. This model uses mathematical modelling to investigate the downstream effects of natural killer cells' activation (KIR2DL4) receptor after stimulation by key ligand (HLA-G) on pbNK cells. Development of this large pathway is based on a comprehensive qualitative description of pbNKs' intracellular signalling pathways leading to chemokine and cytotoxin secretion, obtained from the KEGG database (https://www.genome.jp/pathway/hsa04650). From this qualitative description we built a quantitative model for the pathway, reusing existing curated models where possible and implementing new models as needed. This model employs a composite approach for generating modular models. The approach allows for the construction of large-scale complex model by combining component of sub-models that can be modified individually. This large pathway consists of two published sub-models; the Ca²⁺ model and the NFAT model, and a newly built FCεRIγ sub-model. The full pathway was fitted to published dataset and fitted well to one of two secreted cytokines. The model can be used to predict the production of IFNγ and TNFα cytokines.•Development of pathway and mathematical model•Reusing existing curated models and implementing new models•Model optimization and analysis.