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Deciphering Signaling Pathway Networks to Understand the Molecular Mechanisms of Metformin Action

Fig 3

Metformin-specific signaling pathway network (SPNetwork).

A) A four-way Venn diagram summarizes the number of shared genes among metformin upstream genes represented by ‘Upstream genes’, metformin downstream genes (‘TF genes’), metformin upstream extended genes in the metformin upstream network (‘Upstream extended genes’), and metformin downstream extended genes in the metformin downstream network (‘Downstream extended genes’). B) Metformin-specific SPNetwork with 477 nodes and 1366 edges. The nodes and edges in orange correspond to nodes and edges only in the metformin upstream network. The nodes and edges in green correspond to the nodes and edges only in the metformin downstream network. And the nodes and edges in red correspond to the nodes and edges common to the metformin upstream network and the metformin downstream network. C) Degree distributions and average degrees (vertical lines) of the four gene sets in the metformin-specific SPNetwork. The four gene sets are 41 common nodes, 174 nodes only in the metformin upstream network (SPNetwork_up), 262 nodes only in the metformin downstream network, all 477 nodes in the metformin-specific SPNetwork (SPNetwork_down). The Y-axis represents the proportion of proteins having a specific degree. D) The subnetwork of the 38 hub nodes extracted from metformin-specific SPNetwork. The legends for orange nodes and edges, red nodes and edges, and green nodes and edges are same as those in the subFig B. The nodes in yellow correspond to the genes that exist in the pathway ‘MAPK signaling pathway’ according to KEGG annotation.

Fig 3

doi: https://doi.org/10.1371/journal.pcbi.1004202.g003