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. 2008 Jan 31;2:11.
doi: 10.1186/1752-0509-2-11.

Evidence of Probabilistic Behaviour in Protein Interaction Networks

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Free PMC article

Evidence of Probabilistic Behaviour in Protein Interaction Networks

Joseph Ivanic et al. BMC Syst Biol. .
Free PMC article

Abstract

Background: Data from high-throughput experiments of protein-protein interactions are commonly used to probe the nature of biological organization and extract functional relationships between sets of proteins. What has not been appreciated is that the underlying mechanisms involved in assembling these networks may exhibit considerable probabilistic behaviour.

Results: We find that the probability of an interaction between two proteins is generally proportional to the numerical product of their individual interacting partners, or degrees. The degree-weighted behaviour is manifested throughout the protein-protein interaction networks studied here, except for the high-degree, or hub, interaction areas. However, we find that the probabilities of interaction between the hubs are still high. Further evidence is provided by path length analyses, which show that these hubs are separated by very few links.

Conclusion: The results suggest that protein-protein interaction networks incorporate probabilistic elements that lead to scale-rich hierarchical architectures. These observations seem to be at odds with a biologically-guided organization. One interpretation of the findings is that we are witnessing the ability of proteins to indiscriminately bind rather than the protein-protein interactions that are actually utilized by the cell in biological processes. Therefore, the topological study of a degree-weighted network requires a more refined methodology to extract biological information about pathways, modules, or other inferred relationships among proteins.

Figures

Figure 1
Figure 1
Evidence of degree-weighted connectivity in nine PPI networks. a, Homo sapiens (human); b, Drosophila melanogaster (fruit fly); c-e, Saccharomyces cerevisiae (yeast): Yeast-DIP, Yeast-CORE, Yeast-Y2H; f, Escherichia coli (bacterium); g-h, Caenorhabditis elegans (nematode): Worm-Y2H, Worm-CORE; i, Plasmodium falciparum (malaria-causing parasite). For k1k2 > 10, probabilities of interaction P(k1, k2) were ordered by k1k2 and averaged in groups of 10.
Figure 2
Figure 2
Distance profiles in two protein-protein interaction networks. a, Homo sapiens; b, Drosophila melanogaster. Distances shown as average shortest path lengths L(k1, k2) between proteins of degrees k1 and k2.
Figure 3
Figure 3
Degree weighted connectivity in the Erdös-Rényi random graph model equivalent to the PPI network of P. falciparum (1304 nodes, 2745 edges). Probabilities of interaction P(k1, k2) are calculated for 104 realizations, which are then averaged over the number of simulated networks that contain nodes of degree k1 and k2.

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