Protein–protein interaction network reflecting the molecules and pathways implicated in megakaryopoiesis, the formation of platelets, thrombosis, and hemostasis. (A) PPIN of 1684 nodes (proteins) connected by 5360 edges (biochemical reactions). The 1517 first-order interacting nodes and all but 24 of the 5360 edges were obtained from the Reactome (n = 3625) and IntAct (n = 1711) databases. The 24 edges were added on the basis of manual literature curation. (B) The 200 baits are colored as per the Venn diagram, except for the 8 baits present in >1 category, which are pink, and the 8 prototype proteins involved in the synthesis of thromboxane and signaling via the thromboxane receptor (Tbxa2r) pathway. The Venn diagram shows the 3 gene sets in ochre, blue, and purple for the ThromboGenomics HTS test platform gene set,⁸²  the platelet volume and count GWAS gene set,¹  or the gene set identified by ChIP-seq in human megakaryocytes and showing binding of all 5 transcription factors (Fli1, Gata1, Gata2, Runx1, and Tal1) at their promoter,¹¹⁰  respectively. (C-D) Subnetworks retrieved from the PPIN in A. (C) A subnetwork of 156 nodes and 874 edges obtained by retrieving the first-order interactors of Tbxa2r, the receptor for thromboxane. (D) A subnetwork of 26 nodes and 42 edges involved in the synthesis of thromboxane and obtained by selecting the first-order interactors of Tbxas1 (thromboxane synthase 1) and Pla2g4a (phospholipase A2). The red nodes in C and D are a set of prototype proteins related to thromboxane synthesis and signaling and the other colored nodes are baits. The surface areas of the red colored nodes in A and all colored nodes in C and D reflect their transcript level determined by sequencing of RNA from human megakaryocytes (data retrieved from Chen et al).¹⁰³  An interactive version of the network, containing gene expression levels and other annotation features, is available for download in Cytoscape format from the supplemental Data.