Figure 5

Relative predictive power of functional and physical protein networks. (a) Median values of predictive power (area under the receiver operating characteristic [ROC] curve [AUC]) across 100 loss-of-function phenotypes are plotted versus the median fraction of each seed gene set covered by a network (coverage; measured as the fraction of seed genes with at least one linkage in the network). Five networks are compared: the functional yeast network (YeastNet v. 2 [24]) and four versions of the network of yeast physical protein interactions (Database of Interacting Proteins [DIP] [45], Probabilistic Integrated Co-complex [PICO] [29], Munich Information Center for Protein Sequences [MIPS] physical complexes [44], and Collins and coworkers [43]). DIP, PICO, and YeastNet are each evaluated at two reported confidence thresholds. The YeastNet functional gene network shows considerably higher predictive power than for the networks composed only of physical interactions; the full YeastNet shows higher predictive power than a more confident core set of the top 47,000 linkages, indicating that the lower confidence linkages nonetheless add predictive power. Error bars indicate the first and third quartiles. Panels b and c show example seed gene sets (green circles) and their network connections, indicating functional linkages in grey lines, physical interactions in thin black lines, and both functional and physical interactions in thick black lines. (b) Genes whose deletion increases cellular chitin levels [33] (AUC = 0.87), whose prediction relies upon a mix of physical and functional interactions. (c) Genes whose deletion confers sensitivity at 5 generations in synthetic complete medium lacking threonine [4] (AUC = 0.65), whose prediction derives predominantly from functional linkages.