PDGF

Trairatphisan et al. (Trairatphisan et al., 2016) applied the optPBN toolbox to investigate the deregulated PDGF (Platelet-Derived Growth Factor) signalling in the context of GIST (Gastro-Intestinal Stromal Tumor, a type of mesenchymal neoplasm of the gastro-intestinal tract). Specifically, the way the constitutively active PDGF receptor maintains the cancer cells in a proliferative state is not known, because of the interlocking of the different signaling pathways involved. The study helped filling that gap, by identifying that significant cross-talk exists between the PI3K pathway and the MAPK pathway in this case. The study also demonstrated that it is possible to train the logical model on single perturbation experiments only and predict the behavior of the system under combined perturbations correctly. The diagram of the network considered for the study is reproduced here.

The model contains 30 nodes with 38 interactions (19 interactions are optimized). There exists one logical gate integrating the signal from Grb2SOS and GabSOS (OR gate).
The model contains 6 experimental conditions with 9 inputs and 6 outputs.

Model Summary (Number of …)	PDGF
Nodes	30
(optimized) Parameters / Interactions	19
Logical gates	1
Inputs	9
Outputs	6
Experimental conditions	6
Optimisation time	1.3 seconds

The input files for this study are provided as Excel (.xlsx) files. Model fitting should be completed in a few seconds on a standard desktop computer. In our hands, the optimal fitting cost is 0.1459.