Abundance in Protein Networks Figure 2. Relationship between protein degree and abundance in the raw E. coli TAP Butland PPI network [10] using the gene expression measurements of Covert et al. [48]. (A)–(D), see Figure 1 legend. doi:10.1371/journal.pone.0005815.g002 and the GE measurement data set of Covert et al. (Figure 2C and D), where the degree/abundance relationship appears more pronounced. Therefore, it is possible that the TAP method is detecting interactions that are influenced by the cellular concentrations of the proteins. While this finding may not be surprising, as the TAP method expresses tagged bait and potential prey ORFs from their natural chromosomal locations, it does imply that raw TAP-determined PPI networks incorporate a probabilistic, or random, element. The higher the cellular abundance of a protein, the more often it is likely to be detected in purifications and, therefore, the more interactions it will be construed to be involved in. Although the correlation coefficients given here are not large, it is known that mRNA and protein abundance measurements contain many sources of variation due to technical and biological factors. The HMS-PCI technique to isolate and identify co-purifying proteins [6] is very similar to that used in the TAP studies [5,8], as it uses an affinity purification method to isolate complexes. However, rather than express tagged ORFs from their native environments, as in the TAP studies, Ho et al. express tagged ORFs from plasmids containing GAL1 promoters. It is unclear how this latter non-native delivery system affects the cellular abundances of tagged baits but one might expect the prey proteins to have concentrations similar to those of normal growth conditions. Not surprisingly, perhaps, we also find statistically significant correlations between degree and abundance for the Ho PPI data set. Correlation coefficients are again modest, lying between 0.17 and 0.28 (Table 1), but all P-values are less than 0.0001, suggesting a statistically significant relationship between degree and abundance for the Ho data set. Therefore, it would seem that general affinity purification methods are detecting interactions that are somewhat mediated by the proteins’ cellular abundances. Without counter-example PPI data sets that show no correlation between degree and abundance, one might expect the findings here to be biologically relevant, i.e., on the average, PLoS ONE | www.plosone.org 5 June 2009 | Volume 4 | Issue 6 | e5815