Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations

Áron R. Perez-Lopez, Kristóf Z. Szalay, Dénes Türei, Dezso Módos, Katalin Lenti, T. Korcsmáros, P. Csermely

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish
Article number10182
JournalScientific Reports
Volume5
DOIs
Publication statusPublished - May 11 2015

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Drug-Related Side Effects and Adverse Reactions
Pharmaceutical Preparations
Proteins
Colorectal Neoplasms
Protein Interaction Maps
Drug Design
Type 2 Diabetes Mellitus
Safety

ASJC Scopus subject areas

  • General

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Targets of drugs are generally, and targets of drugs having side effects are specifically good spreaders of human interactome perturbations. / Perez-Lopez, Áron R.; Szalay, Kristóf Z.; Türei, Dénes; Módos, Dezso; Lenti, Katalin; Korcsmáros, T.; Csermely, P.

In: Scientific Reports, Vol. 5, 10182, 11.05.2015.

Research output: Contribution to journalArticle

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