BMC Genomics 2008, 9:461 http://www.biomedcentral.com/1471-2164/9/461 system (v2.0) assigned scores to the 126,896 physical interactions in DroID (excluding genetic interactions). Of these, 28,259 (22.3%) interactions received a score above 0.5, distinguishing them as the high confidence set. These scores should help biologist focus on the most reliable subset of the data for future studies. For example, net- works and subnetworks can be filtered based on user- defined confidence limits to accommodate analyses that tolerate different levels of uncertainty. Gene expression correlation In addition to physical protein-protein interactions and genetic interactions, gene expression data can be a valua- ble tool for linking together genes that may function together. It has been shown, for example, that genes with correlated expression patterns are more likely to function together in common biological processes (e.g., [41,42]), and at least in yeast, proteins encoded by co-expressed genes are more likely to participate in direct physical inter- actions than random pairs [48]. To help reveal relevant functional linkages, every gene pair in DroID is annotated with gene expression correlation values. Consistent with findings in yeast, we found that the physical protein-pro- tein interactions in DroID are encoded by gene pairs with significantly higher expression correlations than random gene pairs (p-value < 2.2*10-16, Figure 2A and Figure 3). In addition, higher expression correlation values were seen for gene pairs that genetically interact, and therefore are likely to function in common biological processes (Figure 2A). Interestingly, the Drosophila physical interac- tions that overlap with interologs detected in other species have a significantly higher expression correlation than the remainder of the physical interactions (p-value < 2.2*10- 16, Figure 2B), suggesting that conserved interactions involve proteins that are more likely to be co-expressed than non-conserved interactions. It is noteworthy that the average correlation values are not very high (e.g., 0.13 for the DroID physical interactions) and that many gene pairs have a negative correlation. This result is not surprising for a multi-cellular organism in which functionally relevant interactions can occur between pairs of proteins even if they are only co-expressed during a fraction of develop- mental time or in just one or a few tissues. Viewing interaction data in the context of gene expression data Gene expression data can also be used to view interaction data in a dynamic context. Most gene and protein interac- EFxigpurersesi2on correlation comparison Expression correlation comparison. Boxplots of average expression correlations of different interaction sets. (A) Com- parison between random pairs of genes not known to interact (Random), all physical interactions in DroID (Physical), including interactions detected with Drosophila proteins and those predicted based on human, worm, and yeast physical interactions (Table 1), and genetic interactions (Genetic). (B) Difference of expression correlations between putative conserved and puta- tive non-conserved fly physical interactions. The conserved set includes Drosophila physical interactions that overlap with any of the three sets of predicted physical interactions, while the non-conserved set contains the rest of the physical interactions. Page 6 of 9 (page number not for citation purposes)