Network-based tools for the identification of novel drug targets

I. Farkas, T. Korcsmáros, István A. Kovács, Ágoston Mihalik, Robin Palotai, Gábor I. Simkó, Kristóf Z. Szalay, M. Szalay, T. Vellai, Shijun Wang, P. Csermely

Research output: Article

66 Citations (Scopus)

Abstract

In the past few years, network-based tools have become increasingly important in the identification of novel molecular targets for drug development. Systems-based approaches to predict signal transduction-related drug targets have developed into an especially promising field. Here, we summarize our studies, which indicate that modular bridges and overlaps of protein-protein interaction and signaling networks may be of key importance in future drug design. Intermodular nodes are very efficient in mediating the transmission of perturbations between signaling modules and are important in network cooperation. The analysis of stress-induced rearrangements of the yeast interactome by the ModuLand modularization algorithm indicated that components of modular overlap are key players in cellular adaptation to stress. Signaling crosstalk was much more pronounced in humans than in Caenorhabditis elegans or Drosophila melanogaster in the SignaLink (http://www.SignaLink.org) database, a uniformly curated database of eight major signaling pathways. We also showed that signaling proteins that participate in multiple pathways included multiple established drug targets and drug target candidates. Lastly, we caution that the pervasive overlap of cellular network modules implies that wider use of multitarget drugs to partially inhibit multiple individual proteins will be necessary to modify specific cellular functions, because targeting single proteins for complete disruption usually affects multiple cellular functions with little specificity for a particular process. Tools for analyzing network topology and especially network dynamics have great potential to identify alternative sets of targets for developing multitarget drugs.

Original languageEnglish
Article numberpt3
JournalScience Signaling
Volume4
Issue number173
DOIs
Publication statusPublished - máj. 17 2011

Fingerprint

Pharmaceutical Preparations
Proteins
Databases
Protein Interaction Maps
Drug Design
Caenorhabditis elegans
Signal transduction
Protein Transport
Drosophila melanogaster
Crosstalk
Signal Transduction
Yeast
Yeasts
Topology

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Network-based tools for the identification of novel drug targets. / Farkas, I.; Korcsmáros, T.; Kovács, István A.; Mihalik, Ágoston; Palotai, Robin; Simkó, Gábor I.; Szalay, Kristóf Z.; Szalay, M.; Vellai, T.; Wang, Shijun; Csermely, P.

In: Science Signaling, Vol. 4, No. 173, pt3, 17.05.2011.

Research output: Article

Farkas, I. ; Korcsmáros, T. ; Kovács, István A. ; Mihalik, Ágoston ; Palotai, Robin ; Simkó, Gábor I. ; Szalay, Kristóf Z. ; Szalay, M. ; Vellai, T. ; Wang, Shijun ; Csermely, P. / Network-based tools for the identification of novel drug targets. In: Science Signaling. 2011 ; Vol. 4, No. 173.
@article{1f226e9e892e4c7288bfe3d4fe2b0d23,
title = "Network-based tools for the identification of novel drug targets",
abstract = "In the past few years, network-based tools have become increasingly important in the identification of novel molecular targets for drug development. Systems-based approaches to predict signal transduction-related drug targets have developed into an especially promising field. Here, we summarize our studies, which indicate that modular bridges and overlaps of protein-protein interaction and signaling networks may be of key importance in future drug design. Intermodular nodes are very efficient in mediating the transmission of perturbations between signaling modules and are important in network cooperation. The analysis of stress-induced rearrangements of the yeast interactome by the ModuLand modularization algorithm indicated that components of modular overlap are key players in cellular adaptation to stress. Signaling crosstalk was much more pronounced in humans than in Caenorhabditis elegans or Drosophila melanogaster in the SignaLink (http://www.SignaLink.org) database, a uniformly curated database of eight major signaling pathways. We also showed that signaling proteins that participate in multiple pathways included multiple established drug targets and drug target candidates. Lastly, we caution that the pervasive overlap of cellular network modules implies that wider use of multitarget drugs to partially inhibit multiple individual proteins will be necessary to modify specific cellular functions, because targeting single proteins for complete disruption usually affects multiple cellular functions with little specificity for a particular process. Tools for analyzing network topology and especially network dynamics have great potential to identify alternative sets of targets for developing multitarget drugs.",
author = "I. Farkas and T. Korcsm{\'a}ros and Kov{\'a}cs, {Istv{\'a}n A.} and {\'A}goston Mihalik and Robin Palotai and Simk{\'o}, {G{\'a}bor I.} and Szalay, {Krist{\'o}f Z.} and M. Szalay and T. Vellai and Shijun Wang and P. Csermely",
year = "2011",
month = "5",
day = "17",
doi = "10.1126/scisignal.2001950",
language = "English",
volume = "4",
journal = "Science Signaling",
issn = "1937-9145",
publisher = "American Association for the Advancement of Science",
number = "173",

}

TY - JOUR

T1 - Network-based tools for the identification of novel drug targets

AU - Farkas, I.

AU - Korcsmáros, T.

AU - Kovács, István A.

AU - Mihalik, Ágoston

AU - Palotai, Robin

AU - Simkó, Gábor I.

AU - Szalay, Kristóf Z.

AU - Szalay, M.

AU - Vellai, T.

AU - Wang, Shijun

AU - Csermely, P.

PY - 2011/5/17

Y1 - 2011/5/17

N2 - In the past few years, network-based tools have become increasingly important in the identification of novel molecular targets for drug development. Systems-based approaches to predict signal transduction-related drug targets have developed into an especially promising field. Here, we summarize our studies, which indicate that modular bridges and overlaps of protein-protein interaction and signaling networks may be of key importance in future drug design. Intermodular nodes are very efficient in mediating the transmission of perturbations between signaling modules and are important in network cooperation. The analysis of stress-induced rearrangements of the yeast interactome by the ModuLand modularization algorithm indicated that components of modular overlap are key players in cellular adaptation to stress. Signaling crosstalk was much more pronounced in humans than in Caenorhabditis elegans or Drosophila melanogaster in the SignaLink (http://www.SignaLink.org) database, a uniformly curated database of eight major signaling pathways. We also showed that signaling proteins that participate in multiple pathways included multiple established drug targets and drug target candidates. Lastly, we caution that the pervasive overlap of cellular network modules implies that wider use of multitarget drugs to partially inhibit multiple individual proteins will be necessary to modify specific cellular functions, because targeting single proteins for complete disruption usually affects multiple cellular functions with little specificity for a particular process. Tools for analyzing network topology and especially network dynamics have great potential to identify alternative sets of targets for developing multitarget drugs.

AB - In the past few years, network-based tools have become increasingly important in the identification of novel molecular targets for drug development. Systems-based approaches to predict signal transduction-related drug targets have developed into an especially promising field. Here, we summarize our studies, which indicate that modular bridges and overlaps of protein-protein interaction and signaling networks may be of key importance in future drug design. Intermodular nodes are very efficient in mediating the transmission of perturbations between signaling modules and are important in network cooperation. The analysis of stress-induced rearrangements of the yeast interactome by the ModuLand modularization algorithm indicated that components of modular overlap are key players in cellular adaptation to stress. Signaling crosstalk was much more pronounced in humans than in Caenorhabditis elegans or Drosophila melanogaster in the SignaLink (http://www.SignaLink.org) database, a uniformly curated database of eight major signaling pathways. We also showed that signaling proteins that participate in multiple pathways included multiple established drug targets and drug target candidates. Lastly, we caution that the pervasive overlap of cellular network modules implies that wider use of multitarget drugs to partially inhibit multiple individual proteins will be necessary to modify specific cellular functions, because targeting single proteins for complete disruption usually affects multiple cellular functions with little specificity for a particular process. Tools for analyzing network topology and especially network dynamics have great potential to identify alternative sets of targets for developing multitarget drugs.

UR - http://www.scopus.com/inward/record.url?scp=79956334133&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79956334133&partnerID=8YFLogxK

U2 - 10.1126/scisignal.2001950

DO - 10.1126/scisignal.2001950

M3 - Article

C2 - 21586727

AN - SCOPUS:79956334133

VL - 4

JO - Science Signaling

JF - Science Signaling

SN - 1937-9145

IS - 173

M1 - pt3

ER -