RT Journal Article SR Electronic T1 Context-specificity in causal signaling networks revealed by phosphoprotein profiling JF bioRxiv FD Cold Spring Harbor Laboratory SP 039636 DO 10.1101/039636 A1 Steven M. Hill A1 Nicole K. Nesser A1 Katie Johnson-Camacho A1 Mara Jeffress A1 Aimee Johnson A1 Chris Boniface A1 Simon E.F. Spencer A1 Yiling Lu A1 Laura M. Heiser A1 Yancey Lawrence A1 Nupur T. Pande A1 James E. Korkola A1 Joe W. Gray A1 Gordon B. Mills A1 Sach Mukherjee A1 Paul T. Spellman YR 2016 UL http://biorxiv.org/content/early/2016/02/15/039636.abstract AB Summary Signaling networks downstream of receptor tyrosine kinases are among the most extensively studied biological networks. However, it remains unclear whether signaling networks depend on biological context. Signaling networks encode causal influences – and not just correlations – between network components. Here, using a causal framework and systematic time-course assays of signaling proteins, we investigate the context-specificity of signaling networks in a cell line system. We focus on a well-defined set of signaling proteins profiled in four breast cancer cell lines under eight stimulus conditions and inhibition of specific kinases. The data, spanning multiple pathways and comprising approximately 70,000 phosphoprotein and 260,000 protein measurements, provide a wealth of testable, context-specific hypotheses, several of which we validate in independent experiments. Furthermore, the data provide a resource for computational methods development, permitting empirical assessment of causal network learning in a complex, mammalian setting.