Apoptosis

Apoptosis is the process by which cells undergo cell death following some stimuli like DNA damage or contact with ligands like TNFα. This process is frequently deregulated in cancer cells. Schlatter et al. (Schlatter et al., 2009) have studied a Boolean model of apoptosis to investigate the effect of different stimuli on mouse hepatocytes. Their analysis highlights the importance of feedback loops and sheds light on the interconnectedness of pro- and anti-apoptotic molecules. This model was also used to benchmark the optPBN toolbox (Trairatphisan et al., 2014).

The apoptosis model is presented here in graphical form:

The model contains 138 nodes with 160 interactions (41 interactions optimized) and 44 logical gates (24 AND and 20 OR gates) and was fitted to 3 experimental measurements (level of apoptosis, concentration of activated caspase 3, concentration of NFκB). The model contains 6 experimental conditions with 11 inputs and 4 outputs.

Model Summary (Number of …)	Apoptosis
Nodes	138
(optimized) Parameters / Interactions	41
Logical gates	44
Inputs	11
Outputs	4
Experimental conditions	6
Optimisation time	< 15minutes

The input files for this study are provided as Excel (.xlsx) files. Model fitting should be completed in less than 15 minutes on a standard desktop computer. In our hands, the optimal fitting cost is 0.1375.