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 to third neighbors of the central cascade (full: 1811 nodes and 11,527 edges; filtered: 411 nodes and 1959 edges). The combined central network separated into species results in 1618 nodes and 9406 edges in human (Fig. S2), as well as 1061 nodes and 5769 edges in mice (Fig. S3). The filtered combined central network results in 369 nodes and 1646 edges in human, as well as 277 nodes and 1119 edges in mice. The first to the third neighbor network was filtered according to clear genomic or transcriptomic differences (interspecies expression differences > 100 RPKM; expressed > 10 RPKM in one species whereas not in the other; no ortholog found between species according to Inparanoid⁸; connector between those proteins). The human and mouse network 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 evident 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 either species. Second messengers (e.g. Calcium, ATP, ADP) are also shown in grey. The node size increases with high expression differences. Edge colors indicate interactions in both species (grey), in human (blue), in mouse (red) and in the central cascade (dark grey). Selected high protein expression differences which are shown by transcriptomics and proteomics accordingly (Table 1 and Fig. 3) are highlighted by golden asterisks. High binders above 90% percentile were excluded. Abbreviations in the figure are the Entrez gene symbols and the full names are given for all genes in Supplemental Table 1. Supplemental Fig. 4 is a separate png file and a high-resolution version of Fig. 1. It allows to inspect better individual subnetworks around different proteins, in particular around interesting species differences (see asterisks in the figure) and the corresponding protein and gene expression differences between species