Context Specificity in Causal Signaling Networks Revealed by Phosphoprotein Profiling.
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Hill, S., Nesser, N., Johnson-Camacho, K., Jeffress, M., Johnson, A., Boniface, C., Spencer, S., et al. (2017). Context Specificity in Causal Signaling Networks Revealed by Phosphoprotein Profiling.. Cell Systems, 4 (1), 73-83.e10. https://doi.org/10.1016/j.cels.2016.11.013
Signaling networks downstream of receptor tyrosine kinases are among the most extensively studied biological networks, but new approaches are needed to elucidate causal relationships between network components and understand how such relationships are influenced by biological context and disease. Here, we investigate the context specificity of signaling networks within a causal conceptual framework using reverse-phase protein array time-course assays and network analysis approaches. We focus on a well-defined set of signaling proteins profiled under inhibition with five kinase inhibitors in 32 contexts: four breast cancer cell lines (MCF7, UACC812, BT20, and BT549) under eight stimulus conditions. The data, spanning multiple pathways and comprising ∼70,000 phosphoprotein and ∼260,000 protein measurements, provide a wealth of testable, context-specific hypotheses, several of which we experimentally validate. Furthermore, the data provide a unique resource for computational methods development, permitting empirical assessment of causal network learning in a complex, mammalian setting.
breast cancer cell lines, casual networks, computational systems biology, context-specific networks, data resource, empirical assessment, network inference, protein signaling networks, reverse-phase protein array data
This work was supported by the National Institutes of Health National Cancer Institute (grant U54 CA112970 to J.W.G., G.B.M., S.M., and P.T.S.). S.M.H. and S.M. were supported by the UK Medical Research Council (unit program numbers MC_UP_1302/1 and MC_UP_1302/3). S.M. was a recipient of a Royal Society Wolfson Research Merit Award. The MD Anderson Cancer Center RPPA Core Facility is funded by the National Institutes of Health National Cancer Institute (Cancer Center Core Grant CA16672).
External DOI: https://doi.org/10.1016/j.cels.2016.11.013
This record's URL: https://www.repository.cam.ac.uk/handle/1810/262697