We compute the BC gene enrichments of central and noncentral genes. We find that with respect to GDC, enrichments in each of the four BC gene categories are much higher for central genes, ranging between 23.5% and 36.4%, than enrichments for [57] , and the authors describe the algorithm as follows. In phase 1, nodes 1, 4, 8, 12, and 16 are colored black as members of an independent DS. In phase 2, nodes 2, 9, and 11 are colored dark grey as connectors that connect nodes in the independent DS resulting from phase 1. In phase 3, the connected DS resulting from phase 2 is pruned to reduce it size by removing node 16 from the DS (no other nodes can be removed without violating the requirement of producing a connected DS of the graph). In panel B, all nodes are initially in the DS and then nodes are visited in order of their increasing degrees and removed from the DS if the resulting DS is a valid connected DS of the graph. That is, nodes are removed in the following order: 3, 16, 2, 4, 7, 10, 13, 14, 15, and 9. The resulting DS therefore contains the remaining nodes: 1, 5, 6, 8, 11, and 12. Clearly, the DS produced by DS-DC (black nodes in panel B) is smaller than the DS produced by DS-RAI (black and dark grey nodes in panel A). doi:10.1371/journal.pone.0023016.g004 non-central genes, ranging between 1.6% and 9.5% (Figure 6 A) . These enrichments are statistically significant for central genes, with p-valuesƒ10 {11 , while for non-central genes they are not, with p-values~1 (see Methods). As expected, if we choose lower k, e.g., 1%, precision is even higher (although recall is lower): out of the top 1%~91 of the most GDC-central proteins in the network, 55% (i.e., 47 of them) are aging genes, 45% (i.e., 41 of them) are cancer genes, 71.5% (i.e., 65 of them) are HIV genes, and 42.9% (i.e., 39 of them) are PI genes (Figure 7) . Also, we measure the enrichment in drug targets of BC genes (i.e., of each of the four BC gene categories: ''A'', ''C'', ''HIV'', and ''PI'' defined above) that are GDC-central and of BC genes that are non-GDC-central. We hypothesize that higher GDC of nodes in the PPI network reflects their functional importance. Proteins that are targeted by drugs are clearly functionally important. Hence, we examine whether the sets of BC genes that are GDC-central contain more drug targets than the sets of BC genes that are non-GDC-central. Indeed, we find that enrichments in drug targets are higher for BC genes that are GDC-central than for BC genes that are non-GDC-central (Figure 6 B) . Furthermore, these enrichments in drug targets are statistically significant for GDC-central BC genes (with the exception of GDC-central HIV genes), with p-valuesƒ0:047, while for non-GDC-central BC genes they are not, with p-values §0:9 (see Methods).