Distinctive Behaviors of Druggable Proteins in Cellular Networks

27Citations
Citations of this article
82Readers
Mendeley users who have this article in their library.

Abstract

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/.

Cite

CITATION STYLE

APA

Mitsopoulos, C., Schierz, A. C., Workman, P., & Al-Lazikani, B. (2015). Distinctive Behaviors of Druggable Proteins in Cellular Networks. PLoS Computational Biology, 11(12). https://doi.org/10.1371/journal.pcbi.1004597

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free