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Context-specificity in causal signaling networks revealed by phosphoprotein profiling
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Hill, Steven M. (Mark), Nesser, Nicole K., Johnson-Camacho, Katie, Jeffress, Mara, Johnson, Aimee, Boniface, Chris, Spencer, Simon E. F., Lu, Yiling, Heiser, Laura M., Lawrence, Yancey, Pande, Nupur T., Korkola, James, Gray, Joe W., Mills, Gordon B., Mukherjee, Sach and Spellman, Paul T. (2017) Context-specificity in causal signaling networks revealed by phosphoprotein profiling. Cell Systems, 4 (1). 73-83.e10. doi:10.1016/j.cels.2016.11.013 ISSN 2405-4712.
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Official URL: http://dx.doi.org/10.1016/j.cels.2016.11.013
Abstract
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.
Item Type: | Journal Article | ||||||||||||||||||
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Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Statistics | ||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Protein-tyrosine kinase, Breast -- Cancer -- Research | ||||||||||||||||||
Journal or Publication Title: | Cell Systems | ||||||||||||||||||
Publisher: | Cell Press | ||||||||||||||||||
ISSN: | 2405-4712 | ||||||||||||||||||
Official Date: | 25 January 2017 | ||||||||||||||||||
Dates: |
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Volume: | 4 | ||||||||||||||||||
Number: | 1 | ||||||||||||||||||
Page Range: | 73-83.e10 | ||||||||||||||||||
DOI: | 10.1016/j.cels.2016.11.013 | ||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||
Date of first compliant deposit: | 22 December 2016 | ||||||||||||||||||
Date of first compliant Open Access: | 21 June 2017 | ||||||||||||||||||
Funder: | National Institutes of Health (U.S.) National Cancer Institute (NIH/NCI), Medical Research Council (Great Britain) (MRC), Royal Society (Great Britain). Wolfson Research Merit Award (RSWRMA) | ||||||||||||||||||
Grant number: | Grant U54 CA112970, Core Grant CA16672 (NIH/NCI), MC_UP_1302/1, MC_UP_1302/3 (MRC) | ||||||||||||||||||
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