Network Neighbors of Drug Targets Contribute to Drug Side-Effect Similarity
2011

Understanding Drug Side Effects Through Protein Networks

Sample size: 1534 publication Evidence: moderate

Author Information

Author(s): Brouwers Lucas, Iskar Murat, Zeller Georg, van Noort Vera, Bork Peer

Primary Institution: Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany

Hypothesis

How much do drug side effects relate to the proximity of their target proteins in a molecular network?

Conclusion

Only a small fraction of drug side-effect similarities is due to drugs targeting proteins that are close in the network, while most similarities arise from shared drug targets.

Supporting Evidence

  • 5.8% of side-effect similarities are due to drugs targeting proteins close in the network.
  • 64% of side-effect similarities arise from overlapping drug targets.
  • Drugs targeting proteins with fewer interactions are more likely to have similar side effects.

Takeaway

This study looks at how drugs can have similar side effects if their target proteins are close together in a network, but it turns out that most similarities come from drugs sharing the same target.

Methodology

The study used a pathway neighborhood measure to assess the closeness of drug pairs based on their target proteins in the human protein-protein interaction network.

Limitations

The study only accounts for direct neighbors in the network, potentially underestimating the role of protein interactions in causing adverse drug effects.

Statistical Information

P-Value

p<0.01

Statistical Significance

p<0.01

Digital Object Identifier (DOI)

10.1371/journal.pone.0022187

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