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2015 ; 11
(12
): e1004597
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Distinctive Behaviors of Druggable Proteins in Cellular Networks
#MMPMID26699810
Mitsopoulos C
; Schierz AC
; Workman P
; Al-Lazikani B
PLoS Comput Biol
2015[Dec]; 11
(12
): e1004597
PMID26699810
show ga
The interaction environment of a protein in a cellular network is important in
defining the role that the protein plays in the system as a whole, and thus its
potential suitability as a drug target. Despite the importance of the network
environment, it is neglected during target selection for drug discovery. Here, we
present the first systematic, comprehensive computational analysis of
topological, community and graphical network parameters of the human interactome
and identify discriminatory network patterns that strongly distinguish drug
targets from the interactome as a whole. Importantly, we identify striking
differences in the network behavior of targets of cancer drugs versus targets
from other therapeutic areas and explore how they may relate to successful drug
combinations to overcome acquired resistance to cancer drugs. We develop,
computationally validate and provide the first public domain predictive algorithm
for identifying druggable neighborhoods based on network parameters. We also make
available full predictions for 13,345 proteins to aid target selection for drug
discovery. All target predictions are available through canSAR.icr.ac.uk.
Underlying data and tools are available at
https://cansar.icr.ac.uk/cansar/publications/druggable_network_neighbourhoods/.
free
free
free
