fig4

Figure 4. Transkingdom network analysis points to potential bacterial regulators of cholestyramine effects on the host. (A) Transkingdom network between genes, phenotypes, and ASVs. ASV outlines reflect the heatmap group from Figure 3 to which the microbes belong (heatmap #1 = black, #2 = purple, #3 = orange). Edges represent significant Spearman correlations (Spearman P-value < 0.05) and are colored based on Spearman’s rho coefficients (blue: negative correlation, red: positive correlation). Nodes are colored based on the fold-change direction (red: up, blue: down) of the node between the WD+Ch group and the WD group (Mann-Whitney U P-value < 0.05). ASV node size is based on log-transformed abundance; (B) BiBC-degree distribution of all nodes, the highest of which are labeled; (C) Heatmap of abundances of top five ASVs ranked on BiBC-degree distribution; (D) Abundances of the top two ASVs, ***P < 0.001; (E) 2D-contour histogram of the nodes with the highest BiBC and degree from 10,000 randomly generated networks. Darker areas indicate higher probabilities of randomly finding a node with that degree and BiBC. Family assignment of the top ASVs in the network: ASV1, Muribaculaceae; ASV49, Lachnospiraceae. ASVs: Amplicon sequence variants; WD: Western diet; WD+Ch: WD with cholestyramine; BiBC: bipartite betweenness centrality.