Fig. 6.

Putative dynamic PPI network for the exercise response. a The putative PPI network for exercise rest or ‘ground state’ contains 513 nodes (genes), after edgeless nodes were removed, and 514 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 exercise state, which contains 426 nodes (genes), after edgeless nodes are removed, and 390 edges (interactions). Nodes (genes) are both up (‘+’ nodes) and down-regulated (‘-’ nodes) and ‘re-wired’ (loss/gain of edges) in the exercise response compared to the rest state depicted in (a). Cluster membership from (a) is transposed onto (b) to highlight how each cluster changes in the exercise 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 1 (red circles), which is most enriched for the ‘Contractile fiber’ functional category becomes extensively fragmented into 10 (mostly two-node) clusters and most genes are down-regulated (19/26) signifying possible dysregulation of this functional modules in the exercise response. Conversely we also see that the Cluster 6 (yellow 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 exercise response. c Depicts the sub-network of (b) whose nodes (genes) are exclusive to the exercise response (i.e. not associated with the training response)