Figure 3

(a) Accounting for the expression coefficients of all protein pairs in Yeast, we observe a bell shaped frequency distribution of the expression correlation coefficient r _P , peaking around 0.0 (initial). Focusing on interacting pairs of Yeast proteins that both have an ortholog in P. falciparum and score above a certain threshold t of the respective hypergeometric clustering coefficient C _vw we observe shifted frequency distributions of the expression correlation coefficients r _P . This observation is further indicated by significant Students t-test scores [see Additional file 1]. (b) Assuming that those interactions constituted by Yeast proteins with an ortholog are conserved as well in P. falciparum, we determined frequency distributions of expression correlation coefficients r _P in this organism. Similarly to (a), we find significant shifts toward enforced coexpression if we focus on conserved interactions in Plasmodium that were embedded in an increasingly cohesive neighborhood in Yeast. Comparing our results to a background distribution of coexpression correlations of all protein pairs in P. falciparum Students t-test scores indicate the significance of our results [see Additional file 1]. (c) The significant shifts toward elevated levels of coexpression allow us to assume that there exists a pronounced correlation between the local cohesiveness of an interaction and the tendency that the involved proteins are coexpressed. Logarithmically binning data points according to their hypergeometric clustering coefficient C _vw in Yeast, we determined the mean expression correlation r _P in each bin, allowing us to observe a positive and significant trend that interacting Yeast proteins having an ortholog in P. falciparum are increasingly coexpressed if they are placed in a cohesive neighborhood (inset, Pearson's r = 0.38, P = 8.8 × 10^-44, Spearman's rank ρ = 0.41, P = 2.8 × 10^-47). Similarly, we observe qualitatively the same trend considering interactions in P. falciparum that have been inferred from Yeast protein interactions which have an ortholog in P. falciparum (Pearson's r = 0.25, P = 1.9 × 10^-27, Spearman's rank ρ = 0.27, P = 2.1 × 10^-30). Error bars indicate the standard deviation from the mean coexpression coefficient in each bin. (d) Concluding, we observe a perturbation persistent coincidence of (i) coexpression of interacting proteins, (ii) an enhanced clustering of their immediate neighborhood and (iii) their elevated tendency to be evolutionary conserved (yellow circles) in S. cerevisiae. Since high clustering around a certain protein interaction coincide well with an elevated reliability the integration of knowledge about the local clustering of an interacting pair of conserved proteins and their tendency to be coexpressed can be used to infer evolutionary core protein interactions in other organisms for which orthologs can be identified.