Emergence of power-law distributions in protein-protein interaction networks through study bias

Protein-protein interaction (PPI) networks are power-law-distributed. However, the experimental procedures for detecting PPIs are affected by technical and study bias. For instance, cancer-associated proteins have received disproportional attention. Moreover, bait proteins in large-scale experiments tend to have many false-positive interaction partners. This raises the question of whether PL distributions in observed PPI networks could be explained by these biases alone. To assess this question, we studied the degree distribution of thousands of PPI networks of controlled provenance. Our findings are supported by mathematical models and extensive simulations and indicate that study bias and technical bias suffice to produce the observed PL distribution. It is, hence, problematic to derive hypotheses about the degree distribution and the true biological interactome from the PL distributions in observed PPI networks. Our study casts doubt on the use of the PL property of biological networks as a modeling assumption or quality criterion in network biology.