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Profiles of Basal and Stimulated Receptor Signaling Networks Predict Drug Response in Breast Cancer Lines

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Mario Niepel1*, Marc Hafner1*, Emily A. Pace2*, Mirra Chung1, Diana H. Chai2, Lili Zhou1, Birgit Schoeberl2 and Peter K. Sorger1

1 HMS LINCS Center, Harvard Medical School, Boston, MA; 2 Merrimack Pharmaceuticals, Cambridge, MA

Sci Signal (2013) 6, ra84.
doi:10.1126/scisignal.2004379 / PMID:24065145 / PMCID:PMC3845839

Overview

This browser widget serves to explore the basal levels and activity of key receptor tyrosine kinases (RTKs) across the panel of 39 breast cancer cell lines studied in Niepel et al. (2013). The set of measurements comprises the abundance and basal phosphorylation of 22 receptors and 3 downstream kinases (ERK, Akt, and Src). Hovering the cursor over the names in the Selection Panel gives a rapid scan over the available data; clicking on a name fixes the choice. (For more info, click on the ⓘ icon.)

USAGE:

  • first, choose the target corresponding to the x-axis by clicking on its abbreviation in the Selection Panel (to the left of the plots); this choice serves as the "anchor" for all subsequent selections, but it can be changed easily, as described below;
  • next, select one or more entities for the y-axis, by clicking on their abbreviations; selecting an entity for the y-axis in this way amounts to selecting a new pair; each newly selected pair gets added to a running list of selected pairs, shown below the Selection Panel; this list of selected pairs persists until the clear button is pressed;
  • to select a different "anchor" for the x-axis, click on the previously selected one to deselect it (this will not affect any previously selected pairs), and then proceed as before; (it is possible to choose the x-axis identifier also for the y-axis, by holding down the shift key while clicking on the x-axis identifier the second time).

NOTES:

  • the thin marks along an axis correspond to cell lines for which the measurement was below the detection threshold for that axis;
  • cross-shaped marks correspond to cell lines for which the measurements were below the detection threshold for both axes (such a cross-shaped mark, when present, always appears on the diagonal, near the lower left corner of the plot);
  • grayed-out targets are those for which no above-threshhold data is available;
  • scatterplot points correspond to cell lines; hovering the cursor over a marker in the scatterplot highlights all the other markers (across all the plots) associated with the same cell line, and, after a short wait, it also brings up the name of this cell line;
  • marker type correspond to the clinical subtype of the cell line (circle for triple negative breast cancer, triangle for HER2-amplified lines, and squares for hormone receptor positive lines);
  • performance and appearance vary across web browsers; in our experience, Chrome is best, followed by Safari, Firefox, Internet Explorer (11+), and Opera, in roughly that order.
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plot type:
    TNBC HER2amp HR+

    Available data and software

    Data Basal profile of receptor tyrosine kinase signaling network measured by ELISA (HMS Dataset #20137). Details Download (.xlsx)
    Data Cell signaling response to growth factors measured by high-throughput microscopy (HMS Dataset #20138). Details Download (.xlsx)
    Data Cell signaling response to cytokines measured by high-throughput microscopy (HMS Dataset #20139). Details Download (.xlsx)
    Data Cell signaling response to growth factors measured by ELISA (HMS Dataset #20140). Details Download (.xlsx)
    Data Transformed datasets used for drug predictions. Details Download (.xlsx)
    Data Drug response data from Heiser et al. (2012) PNAS 109(8), 2724–2729. doi: 10.1073/pnas.1018854108 Download (.xlsx)
    Software A link to our HMS LINCS GitHub for access to the code underlying the interactive scatterplot browser available on this project exploration website. hmslincs at GitHub