Research Paper Volume 16, Issue 17 pp 12168—12190

Figure 4. Mechanistic insights from a combined approach of all tools used by SINGULAR. (A) Recapitulation of well documented cell communication pathway for Macrophage recruitment under the Parabiosis condition. Ccr2 recognizes Ccl2, which initiates a signaling cascade to activate the AP-1 complex, which leads to the activation of chemotaxis genes. (B) Further validation of this well-known pathway from gene set Enrichment analysis of the members of the connected component of TRN and signaling cascade crosstalk for Gnai2 as a signalling intermediate and Fos, Jun and Cepbp as TRN TFs. Values have been averaged from several related functions, full results in Supplementary Table 4. (C) Novel signaling cascade. In Purkinje cells of the cerebellum, Fgf10 binds to Fgfr2, initiating a cascade in which Pkrca leads to the activation of Mapk1, which recruits Runx2 for further expression of the Fgfr2 receptor, as well as a separate Creppb-mediated signaling cascade that ends with Tcf12 activating Pax6, a transcription factor known for its neuroprotective properties. (D) Intersection between druggable activating TFs in DrugBank and the master regulators uncovered in this study. (E) Number of druggable key signaling molecules for every integrated TRN and signalling cascade.