Supplementary Figure 6: Disease map associated with the Loeys-Dietz syndrome and connected disease phenotypes.

The disease map associated to the Loeys-Dietz syndrome (LDS) is an example of annotated network reported by dSysMap (f). The network represents the proteins affected by mutations related to LDS and their first interactors. Different colors for the nodes and edges represent the different types of structural information available for proteins and interactions as detailed in the legend. Small colored circles on the edges and proteins represent mutations mapped on proteins and interactions. Three cases are enlarged from the network. (a) Interaction neighborhood of TGFBR1 (corresponding to the orange shaded circle in the network); structures are available for the kinase and the activin receptor domains. Mutated residues are shown in spheres-representation and colored based on their structural classification (black for buried residues, blue for surface residues and red for interface residues). The Activin receptor domain mediates the interactions with TGFB1, TGFB3 and TGFBR2. The kinase domain mediates the TGFBR1 homomeric interaction, the interaction with FKBP1A and is predicted to mediate the interaction with BMPR2. Red circles highlight the mutations that affect every interaction. (b) Interaction neighborhood of ACVR1 (corresponding to the gray shaded circle in the network). Mutations related to Fibrodysplasia ossificans progressive are located at the ACVR1 homodimeric interface, at the interface with FKBP1A and at the predicted interface with BMPR2 but not at the interface of the homology model for the ACVR1-TGFBR2 interaction. (c) Interaction neighborhood of SMAD3 (corresponding to the pink shaded oval in the network). Mutations for LDS on SMAD3 are found at the interface with SMAD4 (d). Also mutations for Juvenile polyposis syndrome on SMAD4 are found at the interface with SMAD3, even if on a different structural model (e).