We distinguish between interactions that form the main activation routes (“core model”; black edges in Fig 2) and interactions describing feedback and crosstalk mechanisms (“candidate mechanisms”; turquoise edges) that have been reported for special cell types or under certain experimental conditions (SI—$3 Tables).

To select the minimal model structures, we used the discretized fold change (‘increase’, ‘decrease’, ‘no change’, ‘not conclusive’) of the phosphorylation state of two experimental conditions , C1 and C2.

Overall, the ODE models were calibrated on 2200 data points and 25 experimental conditions including four targeted perturbations.

As shown in Fig 6B—6F, model 4_8_12 can reproduce the dynamic behavior of the measured species under diverse experimental conditions .

As shown in Fig 6B—6F, model 4_8_12 can reproduce the dynamic behavior of the measured species under diverse experimental conditions .

Given an interaction graph model, we can predict the possible qualitative responses of the considered proteins for the given experimental conditions using the concept of the dependency matrix [33].

The model was calibrated on 2200 data points and 25 experimental conditions .

For each protein, the fold change of the phosphorylation state measured by quantitative immunoblotting of two different experimental conditions is shown on a logarithmic scale at the indicated time points after 40 ng/ml of HGF stimulation.

Each row refers to one experiment; same experimental conditions are grouped with magenta lines.

Second, experimental conditions that perturb transitions between stem and progenitor states will also perturb the relative proportions of stem and progenitor cells in a heterogeneous population of cells.

Experimentally defining cell-state proportions would make it possible to assess, for each algorithm, how well it identified changes in cell-state proportions across experimental conditions .

To generate such idealized experimental conditions we mixed three different breast cancer cell lines (T47D, SUM159, MDA-MB-231) in defined proportions—for example 1:1:1, 1:2:2, 1:1:0—with 10 mixtures in total.

Accordingly, such screens are frequently performed under a very limited set of experimental conditions .

Since separate studies may often apply either subtly or grossly different experimental conditions , it is not ideal to simply take the accepted consensus of opinion to pair activators and inhibitors together on the basis of their literature defined targets, but it is of interest to reevaluate these relationships in a systematic way.

Rows: different experimental conditions .

In order to approach this problem with minimal reliance on specific experimental conditions , we note several consistent morphological differences between the head and the tail of the worm that are observable in bright-field imaging.

Changes in experimental conditions , the genetic background of the worms under study or changes to the imaging system, can cause significant variation in the features, and thus degrade the classifier performance due to overfitting that fails to take into account experimental variation (Fig 3).

First, in spite of morphological changes due to experimental conditions (Fig 4A), we show the resulting classification scheme operates with consistently high performance in distinguishing the head and the tail of the worm in the new data sets (Fig 4B).