Comparison of the central human and mouse platelet signaling cascade by systems biological analysis

Figures

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  Fig. 1. Differences in the central regulatory cascade (CC) between mouse and human. The center of the human and murine signaling cascade (defined according to systems biological modelling) and its regulators are presented in a combined network including proteomic, transcriptomic, metabolic and ionic interactors (full data Fig. 2). In thick edges, the main regulatory interactions are highlighted. The neighbors up to degree 3 are presented (see methods overview for an exact definition of 1st to 3rd degree neighbors of the CC. Asterisks label confirmed key expression differences of platelet proteins between human and mouse. As the platelet transcript and validated protein content is around 10,181 (9811 protein-coding) in human and 5981 (5814 protein-coding) in mice, large interaction networks can be reconstructed (Human: 18618 high confident interactions and 3524 interactors, Mouse: 10337 high confident interactions and 2114 interactors). In order to outline the important direct and indirect regulators of the central cascade that mark a difference in both species, the combined network shows solely the clear differences (filtered) of a subset of the global interaction network from the first…

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  Fig. 2. Full Network of proteins in and around the central platelet signaling cascade. The human and mouse networks were combined. The differences in both network topologies are shown in color code. The border paint marks expression values (blue for high expression in human; red for high expression in mouse; grey for no considerable expression differences). The node paint marks proteins that occur only in human platelet network (blue), only in human (blue rectangle; non-ortholog proteins), only in murine platelet network (red), only in mouse (red rectangle; non-ortholog proteins), or in both (white). The grey fill color of nodes indicates proteins that are not expressed in platelets in both species, or second messenger (e.g. Calcium, ATP, ADP). The node size increases with high expression differences. Further, edge color indicates interactions in both species (grey), in human (blue), in mouse (red) and in the central cascade (dark grey). High binders above 90% percentile where excluded. Abbreviations in the figure are the Entrez gene symbols and the full names are given for all proteins in Supplemental Table 1. Supplemental Fig. 5 is a separate jpeg file and a high-resolution version of…

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  Fig. 3. Overview of the key expression differences between mouse and human platelet CC. Simplified overview on the found differences for the platelet CC: (i) The key set of proteins that have clear expression differences between mouse and human in the CC or its neighbors as confirmed by transcriptomics and proteomics data are shown (blue rings: higher in human, red rings: higher in mouse). Genetic differences are shown as black points (gene found only in human; for the mouse no such clear difference was found). Moreover, we found cases where there was only expression found in one of the species (“unique”) though in both species the gene was present (blue dot: unique in human; red dot: unique in mouse)