File Name : Figure4A_phases0_1_supplement.png
Caption : Fig. 4 A-D Validation:  PlateletWeb
ADP signalling networks visualized and colored according to the Boolean model phases (A: phase 0; B: phase 1; C: phase 2; D: phase 3). Key phosphorylation events according to experimental data are shown resolved next to each network (phase 0: subnetwork around PKA, phase 1: around Rap 1a/b; phase 2:  around Akt1; phase 3: around TbxA2R). The Boolean model (Fig. 2) is validated here by data on phosphorylation, kinases and substrates not used for setting up the Boolean model but according to experimental data available downloaded from the PlateletWeb knowledgebase (Boyanova et al., 2012). All shown interactions (grey lines), site-specific phosphorylation events (red arrows with labelled sites) and dephosphorylation events (green lines) are extracted from literature studies based on the PlateletWeb knowledge base. Kinase predictions (blue lines) were additionally considered. Kinases are presented as triangles and proteins as circles. Phosphorylated proteins are depicted in red and proteins from the initial ADP model network are shown with blue labels. High resolution pictures of the phases including the complete network with protein names are given in supplementary material, its part B gives experimental data references for all interactions and protein nodes modelled. The rest of the proteins were added for maintaining the network structure and improving the visualization of the signal flow (for example G-proteins). These were not part of the Boolean model. Metabolites and small molecules such as NO and Ca2+ are presented in light blue circles. A large size of the nodes denotes that the protein is associated with a genetic disease. Two important inhibitors of platelet function were additionally included: the P2RY12 receptor inhibitor ticagrelor and the ITGB3 inhibitor abciximab. 


File Name : Figure4B_phases2_3_supplement.png
Caption : Fig. 4 A-D Validation:  PlateletWeb
ADP signalling networks visualized and colored according to the Boolean model phases (A: phase 0; B: phase 1; C: phase 2; D: phase 3). Key phosphorylation events according to experimental data are shown resolved next to each network (phase 0: subnetwork around PKA, phase 1: around Rap 1a/b; phase 2:  around Akt1; phase 3: around TbxA2R). The Boolean model (Fig. 2) is validated here by data on phosphorylation, kinases and substrates not used for setting up the Boolean model but according to experimental data available downloaded from the PlateletWeb knowledgebase (Boyanova et al., 2012). All shown interactions (grey lines), site-specific phosphorylation events (red arrows with labelled sites) and dephosphorylation events (green lines) are extracted from literature studies based on the PlateletWeb knowledge base. Kinase predictions (blue lines) were additionally considered. Kinases are presented as triangles and proteins as circles. Phosphorylated proteins are depicted in red and proteins from the initial ADP model network are shown with blue labels. High resolution pictures of the phases including the complete network with protein names are given in supplementary material, its part B gives experimental data references for all interactions and protein nodes modelled. The rest of the proteins were added for maintaining the network structure and improving the visualization of the signal flow (for example G-proteins). These were not part of the Boolean model. Metabolites and small molecules such as NO and Ca2+ are presented in light blue circles. A large size of the nodes denotes that the protein is associated with a genetic disease. Two important inhibitors of platelet function were additionally included: the P2RY12 receptor inhibitor ticagrelor and the ITGB3 inhibitor abciximab.