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

David B. Blumenthal, Marta Lucchetta, Linda Kleist, Sándor P. Fekete, Markus List, Martin H. Schaefer

Research output: Contribution to journalArticlepeer-review

Abstract

Degree distributions in protein-protein interaction (PPI) networks are believed to follow a power law (PL). However, technical and study biases affect the experimental procedures for detecting PPIs. For instance, cancer-associated proteins have received disproportional attention. Moreover, bait proteins in large-scale experiments tend to have many false-positive interaction partners. Studying the degree distributions of thousands of PPI networks of controlled provenance, we address the question if PL distributions in observed PPI networks could be explained by these biases alone. 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 topology of 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.

Original languageEnglish
JournaleLife
Volume13
DOIs
StatePublished - 11 Dec 2024

Keywords

  • computational biology
  • human
  • power law distributions
  • protein-protein interaction networks
  • study bias
  • systems biology

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