Intracellular Information Processing through Encoding and Decoding of Dynamic Signaling Features
Fig 5
Combination of activation and deactivation kinetics of signaling dynamics stratify late response transcription factor phenotypes.
(A) Late response (58 min) phenotypes for Total AP-1 transcription factor (TF) shown as High, Mid, and Low, represented by red, green, and blue colors, respectively. The red and blue phenotypes were selected from upper and lower margins of the distribution at the late time point, respectively (distribution is illustrated on the right side of the figure), and mid phenotype profiles where selected from the median region of the distribution. The first 250 profiles are shown for each response TF phenotype, selected from their representative statistical regions. The gray background corresponds to spanning of the 100,000 simulations resulting from a dense simultaneous randomization of signaling features (see Methods section for details). (B) The corresponding upstream signaling kinase profiles for FRK, ERK and JNK responsible for shaping the Total AP-1 response TF phenotypes displayed in A. (C) Decision tree displaying the combination rules of signaling features essential to stratify late Total AP-1 downstream response TF phenotypes (red, green and blue). The tree root node represents the most dominant feature, the next branch nodes represent relatively less dominant features, and so on. The width of the tree branch represents the number of cells, and the percentage in each leaf constitutes the proportion of those cells belonging to the respective phenotype, represented via red (High), green (Mid) or blue (Low) color. (D) Scatter plot of the first two dominant signaling features distinctively separating the three Total AP-1 phenotypes in feature-space, shown through dotted lines. These dotted lines are the classifiers estimated by the root, and the first significant branch of the decision tree in C. τ2J and τ1J splices out Total AP-1 late response phenotypes for Total AP-1. (E) Late response phenotypes for ppc-FOS:ppc-JUN TF, shown as red, green and blue. See A for details. (F) The corresponding 250 signaling kinase profiles which shaped ppc-FOS:ppc-JUN TF phenotypes. (G) Decision tree displaying the combination rules of signaling features necessary to stratify the late ppc-FOS:ppc-JUN downstream responses. See C for figure details. (H) Plot showing dominant signaling feature, τ3F, distinctively separating three ppc-FOS:ppc-JUN phenotypes. (I) Late response phenotypes for late ppc-JUN:ppc-JUN response, shown as red, green and blue, respectively. See A for figure details. (J) The corresponding signaling profiles that shaped ppc-JUN:ppc-JUN TF phenotypes. (K) Decision tree displaying the combination rules of signaling features necessary to splice late ppc-JUN:ppc-JUN downstream phenotypes. See C for details. (L) Scatter plot of the first two dominant signaling features, τ1J and τ2J distinctively separating three ppc-JUN:ppc-JUN phenotypes in their feature-space, shown via dotted lines.