Key genes and signaling pathways involved in the crosstalk between islets and liver
(A) Network of trait-correlated islet and liver modules. In total, 8 islet (red circles) and 26 liver (blue circles) modules were defined as associated with insulin secretion traits. Among these 208 (8 × 26) pairs, 8 pairs of highly correlated modules were identified with Pearson coefficient >0.4 (linked with thick lines) and 17 pairs showed coefficient >0.35 and ≤0.4 (linked with thin lines).
(B) Examples of key gene identification between two highly related trait-correlated islet and liver modules (Pearson coefficient >0.4). Each dot represents one gene and “key genes” (the top right of each graph) are those most correlated to a counterpart partner module (correlation >0.5) and also displayed a high module connectivity (membership >0.9).
(C–E) Ingenuity network analyses using islet DEGs as the basis and sequentially adding liver DEGs encoded for proteins that can be secreted at the same time point. The most dominant networks of week 4 (C), 12 (D), and 24 (E) were depicted. The upregulated genes are in red and the downregulated are in green. The molecules marked with stars are derived from liver, and the rest are derived from islets.
See also Figures S4 and S7, and Table S2, S3, S4 and S5.