Abstract
Although it is increasingly being recognized that drug-target interaction networks can be powerful tools for the interrogation of systems biology and the rational design of multitargeted drugs, there is no generalized, statistically validated approach to harmonizing sequence-dependent and pharmacology-dependent networks. Here we demonstrate the creation of a comprehensive kinome interaction network based not only on sequence comparisons but also on multiple pharmacology parameters derived from activity profiling data. The framework described for statistical interpretation of these network connections also enables rigorous investigation of chemotype-specific interaction networks, which is critical for multitargeted drug design.
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Authors and Affiliations
Contributions
J.T.M. performed all of the statistical analyses and created the network visualizations; E.F.J. designed the initial kinome screening panel and supervised the enzymology; N.B.S., P.J.M. and L.K. performed all kinase assays; P.J.H. supervised the research and wrote the manuscript.
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All authors are currently employed by and obtain their salary from Abbott Laboratories.
Supplementary information
Supplementary Text and Figures
Supplementary Methods, Supplementary Figures 1–6 and Supplementary Tables 1 & 2 descriptions (PDF 1153 kb)
Supplementary Table 1
Kinome pKi data with clusters (xls) (XLS 3912 kb)
Supplementary Table 2
Kinome pharmacology interactions (csv) (CSV 3218 kb)
Supplementary Dataset
Kinome pharmacology analysis, .txt file for Pipeline Pilot (XML 557 kb)
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Metz, J., Johnson, E., Soni, N. et al. Navigating the kinome. Nat Chem Biol 7, 200–202 (2011). https://doi.org/10.1038/nchembio.530
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DOI: https://doi.org/10.1038/nchembio.530
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