<p>(A) Hierarchical clustering and heat-map of relative cell viabilities after 28 different treatments. Simulated treatment responses (cell viability changes) were clustered using an unbiased hierarchical method with a Euclidian distance function, resulting in 7 different clusters (pink, black, blue, green, purple, cyan, and orange color) indicated by color bar on the top of heat-map. Each row indicates an individual therapy. Each column indicates an individual in silico cell. Blue to yellow bars: decrease to increase. The asterisk [*] indicates relative cell viability after a combination therapy of AKTi with MEKi. (B–C) Chord diagrams and weighted network diagrams of the representative in silico cells <b>a</b> and <b>b</b>. Chord diagram: each node in the circle represents each protein node in the network model, represented by different colors. The thickness of chord between two protein nodes represents a weight between two protein nodes (weight, <i>w</i><sub><i>ij</i></sub>). The chords are directed, colored by originating sector color. For example, the interaction between <i>RAS_m</i> and RAF is depicted as a light blue chord because the direction is from <i>RAS_m</i> to RAF (<i>RAS_m</i> → RAF; color of <i>RAS_m</i> sector: light blue). Weighted network diagram: the width of each edge represents the weight. A thicker edge represents a larger weight between two proteins. The numerical data used in Fig 4 are included in the third sheet <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.2002930#pbio.2002930.s013" target="_blank">S1 Data</a>. AKT (PKB), protein kinase B; EGFR, epidermal growth factor receptor; ERK, extracellular receptor kinase; HGF, hepatocyte growth factor; MEK, mitogen-activated protein kinase kinase; MET (c-MET), tyrosine-protein kinase Met or hepatocyte growth factor receptor (HGFR); PI3K, phosphoinositide 3-kinase; RAF, rapidly accelerated fibrosarcoma; RAS, rat sarcoma; RAS_m, mutated RAS; RAS_w, wild-type RAS; RSK, ribosomal S6 kinase.</p
