d DATA AND SOFTWARE AVAILABILITY br SUPPLEMENTAL INFORMATION
d DATA AND SOFTWARE AVAILABILITY
Supplemental Information can be found online at https://doi.org/10.1016/j.
We would like to thank the Bodenmiller lab for support and fruitful discussions, the Sommer lab for sharing experimental materials, the Lehner lab and the Mo-simann lab for sharing equipment, and Dr. Vinko Tosevski and Dr. Tess Brodie
at the Mass Cytometry Facility, University of Zurich,€ for support and trouble-shooting help. We would especially like to thank Dr. A.-C. Gingras, Lunen-feld-Tanenbaum Research Institute, for sharing the pDEST vectors used in this study. This work was supported by a Swiss National Science Foundation (SNSF) R’Equip grant, an SNSF Assistant Professorship grant (PP00P3-144874), the European Research Council (ERC) under the European Union’s Seventh Framework Program (FP/2007-2013)/ERC Grant Agreement no. 336921, and an NIH grant (UC4 DK108132).
X.-K.L. and B.B. conceived the study. X.-K.L. performed the experiments, the data processing, and the data analysis. D.S. performed the functional enrich-ment and functional association analysis. A.G. performed the OmniPath anal-ysis. N.D. cloned the phosphatase Malonyl Coenzyme A library. V.R.T.Z. implemented the BP-R2 platform and helped with the data analysis. X.-K.L., D.S., A.G., N.D., V.R.T.Z., J.S.-R., C.v.M., and B.B. performed the biological interpreta-tion. X.-K.L. and B.B. wrote the manuscript with input from all of the authors.
DECLARATION OF INTERESTS
The authors declare no competing interests.
Du, W., and Elemento, O. (2015). Cancer systems biology: embracing complexity to develop better anticancer therapeutic strategies. Oncogene 34, 3215–3225.
Guan, K.L., and Butch, E. (1995). Isolation and characterization of a novel dual specific phosphatase, HVH2, which selectively dephosphorylates the mitogen-activated protein kinase. J. Biol. Chem. 270, 7197–7203.
Krumsiek, J., Suhre, K., Illig, T., Adamski, J., and Theis, F.J. (2011). Gaussian graphical modeling reconstructs pathway reactions from high-throughput metabolomics data. BMC Syst. Biol. 5, 21.
Mattila, E., Pellinen, T., Nevo, J., Vuoriluoto, K., Arjonen, A., and Ivaska, J. (2005). Negative regulation of EGFR signalling through integrin-a1b1-medi-ated activation of protein tyrosine phosphatase TCPTP. Nat. Cell Biol. 7, 78–85.
A census of amplified and overexpressed human cancer genes. Nat. Rev.
controlling growth and sensitivity to therapy-implications for cancer and aging.
Ward, J.H. (1963). Hierarchical Grouping to Optimize an Objective Function.
KEY RESOURCES TABLE
REAGENT or RESOURCE SOURCE IDENTIFIER
Cell Signaling Technology
Chemicals, Peptides, and Recombinant Proteins
Paraformaldehyde Electron Microscopy Sciences Cat# 15710
Maleimido mono amide DOTA (mDOTA) Macrocyclics Cat# B-272
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REAGENT or RESOURCE SOURCE IDENTIFIER
Iridium Fluidigm Cat# 201192A
Maxpar X8 Multimetal labeling kit Fluidigm Cat# 201300
Lanthanide (III) metal isotopes as chloride salts Fluidigm N/A
jetPRIME PolyPlus Cat# 114-15
Recombinant Murine EGF Peprotech Cat# 315-09
vemurafenib Selleckchem Cat# S1267
Integrated raw data and preprocessed data
Experimental Models: Cell Lines
A gift from Dr. Lukas Sommer
The human kinase library plasmid kit Addgene Kit# 1000000014
ORFeome Human Entry Collection Phosphatase Dharmacon Cat# OHS4941
pDEST pcDNA5 FRT TO-eGFP A gift from Dr. Anne-Claude Gingras N/A
pDEST 30 Triple Flag pcDNA5 FRT TO A gift from Dr. Anne-Claude Gingras N/A
Software and Algorithms
Cytobank Cytobank https://www.cytobank.org/
Concatenation tool Cytobank https://support.cytobank.org/hc/en-us/articles/
Normalizer Finck et al., 2013 https://github.com/nolanlab/bead-
Single cell debarcoder Zunder et al., 2015 https://github.com/nolanlab/single-cell-
Lun et al., 2017 https://github.com/BodenmillerGroup/Adnet
t-SNE van der Maaten and Hinton, 2008 https://github.com/jkrijthe/Rtsne
STRING Szklarczyk et al., 2017 https://string-db.org/
Shape-based clustering Genolini et al., 2015 R package ‘kml’
CONTACT FOR REAGENT AND RESOURCE SHARING
Further information and requests for resources and reagents should be directed to and will be fulfilled by the Lead Contact, Bernd Bodenmiller ([email protected]).
EXPERIMENTAL MODEL AND SUBJECT DETAILS