Figure 1

Simulation workflow for in silico tumor model. A, This illustration depicts a representative simulation protocol used for retrospective analysis of gene mutation-drug sensitivity association reported in the Garnett study. The simulation protocol included 3 states: Control or Untriggered state is simulated for 50,000 seconds to allow the biological entities to attain a steady-state concentration. At 50,000 seconds, mutation data is introduced and simulated for an additional 1,25,000 seconds to attain Disease state. For Drug-treated state, we introduce a drug into the system by perturbing the target reaction nodes and simulate the model for 2,00,000 seconds. At the end of this state, we calculate percent change in the indices for cell survival. B, This schematic demonstrates the simulation workflow for creation, optimization and testing of patient-derived GBM cell line profiles in silico. The key steps involved in developing the simulation avatars of the patient-derived GBM cell lines include: Input profiling data reporting relative expression of the different proteins in the cell lines; Iterative testing and alignment of simulation avatars to match experimental data on drugs used for alignment of the network (erlotinib, sorafenib and dasatinib); Locking the simulation avatars; In silico predictions and in vitro testing.