Fig. 7

Putative dynamic PPI network for the training response. a The putative PPI network for untrained or ‘ground state’ contains 199 nodes (genes), after edgeless nodes were removed, and 186 edges (interactions)(see also Fig. 5 and Methods). This network was partitioned by Newman’s fastgreedy community detection (based on network topology only and with no prior information relating to gene function) into forty-three communities or node ‘clusters’. A subset of twenty-eight of these clusters had greater than two nodes (genes) and were found to be significantly enriched for at least one functional category (described by KEGG, Reactome or Gene Ontology). Node colour and shape (i.e. circle, square, up-pointing triangle and down-pointing triangle) signifies cluster membership (only functionally enriched cluster shown in legend). Node size is proportional to node ‘betweeness’ score, with the largest nodes ‘controlling’ the most network ‘traffic’ (along shortest paths). The top twenty ‘bottleneck’ nodes have white labels. b The network for the trained state, which contains 188 nodes (genes), after edgeless nodes are removed, and 176 edges (interactions). Nodes (genes) are both up (‘+’ nodes) and down-regulated (‘-’ nodes) and ‘re-wired’ (loss/gain of edges) in the training response compared to the untrained state depicted in (a). Cluster membership from (a) is transposed onto (b) to highlight how each cluster changes in the trained network state (i.e. common nodes are given the same colour and shape with new nodes depicted by uncoloured circles). For example, it can be seen that Cluster 2 (green circles), which is most enriched for the ‘ErbB signaling pathway/Signaling by PDGF’ functional category becomes fragmented into 4 clusters and all visible genes (edgeless nodes are not depicted) are down-regulated. Conversely we see that the Cluster 1 (red circles), which is most enriched for ‘NADH dehydrogenase/ Mitochondrial respiratory chain complex I’, is mostly up-regulated and remains largely intact, signifying possible coordinated up-regulation of this functional module in the training response. c Depicts the sub-network of (b) whose nodes (genes) are exclusive to the training response (i.e. not associated with the exercise response)