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Fig. 2 | BMC Bioinformatics

Fig. 2

From: Identification, visualization, statistical analysis and mathematical modeling of high-feedback loops in gene regulatory networks

Fig. 2

Example high-feedback topologies. Overall network structure and representative subnetworks are shown for the T cell (ae) and EMT (fj) networks. Left column: Overviews of the strongly connected components of the (a) T cell, (f) EMT, and (k) TRRUST2 networks. be Examples in the T cell network. gj Examples in the EMT network. Each positive feedback loop (e.g. mutual inhibition between PU1 and Bcl11b in b) used by HiLoop to extract the subnetwork is highlighted in a different color. Edges with the same source and target nodes denote a single regulation involved in multiple loops (e.g. repression of PU1 by Runx1 in c). Additional edges induced by the set of nodes involved in the selected, colored cycles are shown in black (e.g. repression of GATA3 by PU1 in e). b A simple Type-I subnetwork of the T cell network. The node involved in all three loops is bolded. c A Type-I subnetwork that is more difficult to notice intuitively. Some regulations are involved in multiple feedback loops and are therefore shown multiple times. HiLoop can add a “logo” (gray panel) summarizing the motif: here, three positive feedback loops joined through PU1. d A Type-II subnetwork of the T-cell network. The gold-colored positive feedback loop connects the red and blue loops. e A Type-II subnetwork that is difficult to notice intuitively, again presented with multiedges and a logo, which for Type-II topologies shows a node from the intersection of each cycle pair. g, h Type-I subnetworks of the EMT network. i, j Type II subnetworks of the EMT network. l A mixed-sign high-feedback subnetwork found in the TRRUST2 network, with logo. Edges involved in negative feedback loops are dashed. m Positive feedback loop (PFL) and high-positive-feedback topology count in each searched network

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