Data Supplement

• 331_Supp_PDF.pdf -

  Fig. S1: Principal Component Analysis of resistant cell line samples and tumor tissue samples. 

  Fig S2. Drug sensitivity correlates with sRGES drug response predictions.

  Fig S3. Single-agent activity of compounds identified in the computational screen.

  Fig. S4. A BRAFi resistance signature is inversely correlated with melanoma overall survival.

  Fig. S5 Identification of compounds that reverse a BRAFi resistance gene expression signature.

  Fig S6. Identification of compounds which re-sensitize BRAFi-resistant cells to vemurafenib.

  Fig. S7. The combination of ibrutinib and vemurafenib reduces colony formation in M229R cells.

  Fig S8. The combination of vemurafenib and ibrutinib increases the number of Annexin V-positive cells but does
  not alter caspase3/7 activity or PARP cleavage.

  Fig S9. BTK mRNA is weakly expressed in M229P/R cells.

  Fig S10. Quantification of BTK knockout efficiency.

  Fig S11. Differential gene expression networks are associated with developmental gene signatures
  
  Fig S12. Expression of ibrutinib targets in M229P/R cells. 

  Fig S13. Ibrutinib does not alter TAZ localization in BRAFi-resistant cells.
  

• Data Supplement 1 -

  Supplemental Data 1: Primers used for PCR amplification of BTK. The PCR primers listed in Supplemental Data 1 were used to amplify the region of the BTK gene which contained the CRISPR cut site. Sequencing was performed with the indicated nested primers. The data from this experiment are summarized in Fig. 2A.
  

• Data Supplement 2 -

  Supplemental Data 2: Results from sRGES analysis. This data table summarizes the results from the computational sRGES analysis. The analytical steps used to generate these data are described in the Materials and Methods section under “OCTAD Datasets and RNA-Sequence processing”, “Disease signature creation”, and “Drug prediction. The results of this analysis are summarized in Figure 1A.