Effect of sampling on topology predictions of protein-protein interaction networks

Currently available protein-protein interaction (PPI) network or 'interactome' maps, obtained with the yeast two-hybrid (Y2H) assay or by co-affinity purification followed by mass spectrometry (co-AP/MS), only cover a fraction of the complete PPI networks. These partial networks display scale-free topologies-most proteins participate in only a few interactions whereas a few proteins have many interaction partners. Here we analyze whether the scale-free topologies of the partial networks obtained from Y2H assays can be used to accurately infer the topology of complete interactomes. We generated four theoretical interaction networks of different topologies ( random, exponential, power law, truncated normal). Partial sampling of these networks resulted in sub-networks with topological characteristics that were virtually indistinguishable from those of currently available Y2H-derived partial interactome maps. We conclude that given the current limited coverage levels, the observed scale-free topology of existing interactome maps cannot be confidently extrapolated to complete interactomes.