Perturbation biology links temporal protein changes to drug responses in a melanoma cell line
Fig 2
Phenotypic and proteomic response to single and drug combinations.
The melanoma cell line A2058 was subjected to 54 drug combinations and the response of 124 (phospho-)proteins and two phenotypes (cell number and apoptosis) was measured at eight time points from 10 minutes to 67 hours. These data were used as input for model inference and prediction. The most informative data involved a subset of the proteins and phospho-proteins (black lines) that underwent the largest changes upon perturbation (AKT-pS473/474, ERK1/2-pT202/T204, cJUN-pS73, and p21) as well as apoptosis (blue line). The remaining 120 proteins and phospho-proteins together with cell counts had a less pronounced response to perturbation. Temporal response (vertical axis) is defined as log2(xperturbed(t)/xunperturbed(t)) where x(t) are concentrations or counts as in Eqs 1 and 2 and DMSO is the unperturbed control.