within up-regulated or down-regulated proteins (intraregulatory links) than between up-and down-regulated proteins (interregulatory links). Among the 5,713 links in the network, the majority (4,854 links, 84.96%) were intraregulatory links ( Figure 2B ). When we measured the fraction of links per protein, intraregulatory links were 3-fold more common than interregulatory links (Whitney-Mann U test, p-value = 7.55610 278 ; Figure 2C ). Furthermore, the shortest path length of proteins connected within intraregulatory links was smaller than that of proteins connected within interregulatory links (Whitney-Mann U test, p-value = 7.55610 2156 ; Figure 2D ). Shortest path length is the minimum number of links connecting one protein to another protein in the network, thus a smaller shortest path length implies that two proteins are more closely related [6] . This result indicates that up-regulated and down-regulated proteins tend to cluster themselves and might have distinct functional roles in the protein functional network.