The context-dependent, combinatorial logic of BMP signaling
Cell-cell communication systems typically comprise families of ligand and receptor variants that function together in combinations. Pathway activation depends in a complex way on which ligands are present and what receptors are expressed by the signal-receiving cell. To understand the combinatorial logic of such a system, we systematically measured pairwise Bone Morphogenetic Protein (BMP) ligand interactions in cells with varying receptor expression. Ligands could be classified into equivalence groups based on their profile of positive and negative synergies with other ligands. These groups varied with receptor expression, explaining how ligands can functionally replace each other in one context but not another. Context-dependent combinatorial interactions could be explained by a biochemical model based on competitive formation of alternative signaling complexes with distinct activities. Together, these results provide insights into the roles of BMP combinations in developmental and therapeutic contexts and establish a framework for analyzing other combinatorial, context-dependent signaling systems.
This deposit contains the data, code, and analysis to recreate the results in the manuscript, 'The combinatorial logic of BMP signaling across contexts.' The processed data and analysis are organized by figures, and the raw data are organized by data type. The code and analysis are written for Matlab 2019a and Python 3. Please see the related publication for more details, and contact the corresponding authors for any questions.
Klumpe, H., Langley, M.A., Linton, J.M., Su, C.J. Antebi, Y.E., Elowitz, M.B. (2020). The combinatorial logic of BMP signaling across contexts (Version 1.0) [Data set]. CaltechDATA. https://doi.org/10.22002/D1.1693 or choose a different citation style.
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