Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations
Author(s)
Type
Journal Article
Abstract
Network-based methods are playing an increasingly important role in drug design. Our main question in this paper was whether the efficiency of drug target proteins to spread perturbations in the human interactome is larger if the binding drugs have side effects, as compared to those which have no reported side effects. Our results showed that in general, drug targets were better spreaders of perturbations than non-target proteins, and in particular, targets of drugs with side effects were also better spreaders of perturbations than targets of drugs having no reported side effects in human protein-protein interaction networks. Colorectal cancer-related proteins were good spreaders and had a high centrality, while type 2 diabetes-related proteins showed an average spreading efficiency and had an average centrality in the human interactome. Moreover, the interactome-distance between drug targets and disease-related proteins was higher in diabetes than in colorectal cancer. Our results may help a better understanding of the network position and dynamics of drug targets and disease-related proteins, and may contribute to develop additional, network-based tests to increase the potential safety of drug candidates.
Date Issued
2015-05-11
Date Acceptance
2015-04-01
Citation
Scientific Reports, 2015, 5, pp.1-9
ISSN
2045-2322
Publisher
Nature Publishing Group
Start Page
1
End Page
9
Journal / Book Title
Scientific Reports
Volume
5
Copyright Statement
© 2015 The Author(s). This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/25960144
PII: srep10182
Subjects
Colorectal Neoplasms
Diabetes Mellitus, Type 2
Drug Delivery Systems
Drug-Related Side Effects and Adverse Reactions
Humans
Neoplasm Proteins
Protein Interaction Maps
Time Factors
Publication Status
Published
Coverage Spatial
England
Article Number
ARTN 10182
Date Publish Online
2015-05-11