A. Comparison of topological measures in identification of important proteins. Networks were inferred as described in the text, varying parameters (see Additional file 3: Table S2), and topological measures calculated (X axis). The enrichment of known pathogen interactors in the top 20% of proteins ranked by each measure was calculated and is shown as the percentage enrichment in the group divided by the enrichment in background. The boxes represent the 25th and 75th percentiles, the bold bar represents the mean, and the dashed bars are at 1.5 times the interquartile range. The enrichment given by differential abundance is shown as a comparison. This figure shows that degree and betweeness perform much better than other, more sophisticated, measures of importance for these networks. B. Comparison of the enrichment of topological sub-types. For the cell culture co-abundance network integrated with PPIs we assessed statistical enrichment in pathogen targets for the following sub-types of topology: NH-NH, non-hub non-bottleneck nodes; HB, hubs; BN, bottlenecks; H-NB, hub non-bottlenecks; B-NH, bottleneck non-hubs; BH, bottleneck hubs. These sub-types were determined as the overlap of the top 20% of nodes ranked by degree (hubs) or betweenness (bottlenecks). The analysis shows that betweenness is the primary driver of importance in these networks similar to observations in directed regulatory networks.