Table 2.

In silico simulation portfolio of the Simulated Cell

Experiment	Purpose	Input parameters	Output parameters
Native simulation	To measure the native phenotypic behavior of the cell lines without intervention	• Node parameters: base activity, base concentration • Edge parameters: direction, type, strength	• Node effects • Attractor scores • In silico verdict on cell fate
Monotherapy response screen	To measure the response of a cell line to a single drug intervention	• Native simulation input parameters • Molecular target profile of compounds	• In silico predicted IC50 values of cell lines/drug • Cell viability
Combination therapy screen	To measure the synergistic effect of two compounds in given dose points	• Monotherapy response input parameters • Dose grid	• In silico predicted synergy scores • Doses in synergistic points • Cell viability
Combination specific biomarker screen	To measure the possible effect of node parameter alterations on synergy	• Combination therapy screen input parameters • Altered node parameters: Under- and overexpression, Loss-and gain-of-function mutations.	• Shift of synergy scores by node parameter perturbations • Shift of cell viability by node parameter perturbations

By using the Simulated Cell, we are able to interrogate the in silico simulatable tumor cells to gather information about their native, untreated behavior and the dose-dependent mono- and combination therapy sensitivity while introducing additional single-node perturbation to the system.