Quantification of uncertainty in a new network model of pulmonary arterial adventitial fibroblast pro-fibrotic signalling.

ABSTRACT: Here, we present a novel network model of the pulmonary arterial adventitial fibroblast (PAAF) that represents seven signalling pathways, confirmed to be important in pulmonary arterial fibrosis, as 92 reactions and 64 state variables. Without optimizing parameters, the model correctly predicted 80% of 39 results of input-output and inhibition experiments reported in 20 independent papers not used to formulate the original network. Parameter uncertainty quantification (UQ) showed that this measure of model accuracy is robust to changes in input weights and half-maximal activation levels (EC₅₀), but is more affected by uncertainty in the Hill coefficient (n), which governs the biochemical cooperativity or steepness of the sigmoidal activation function of each state variabl

SUBMITTER: Wang A 

PROVIDER: S-EPMC7287331 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature