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  • br d QUANTIFICATION AND STATISTICAL ANALYSIS B Data preprocessing and

    2022-05-18


    d QUANTIFICATION AND STATISTICAL ANALYSIS B Data preprocessing and BP-R2 analysis
    B Hierarchical clustering B t-SNE analysis
    B Functional enrichment and association analysis using STRING database
    B Shortest signed directed path analysis using OmniPath B Shape-based clustering
    B Selection of strong signaling dynamic influencing POIs
    B Signaling amplitudes analysis
    d DATA AND SOFTWARE AVAILABILITY
    SUPPLEMENTAL INFORMATION
    Supplemental Information can be found online at https://doi.org/10.1016/j.
    ACKNOWLEDGMENTS
    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).
    AUTHOR CONTRIBUTIONS
    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 SP 600125 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.
    REFERENCES
    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.
    STAR+METHODS
    KEY RESOURCES TABLE
    REAGENT or RESOURCE SOURCE IDENTIFIER
    Antibodies
    Clone D8E9
    Cell Signaling Technology
    Chemicals, Peptides, and Recombinant Proteins
    Paraformaldehyde Electron Microscopy Sciences Cat# 15710
    Maleimido mono amide DOTA (mDOTA) Macrocyclics Cat# B-272
    (Continued on next page)
    Continued
    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
    Selleckchem
    Deposited Data