Fig. 6: The protein network underlying MM drug sensitivity.
a, STRING-db interaction network for the proteins whose abundance in myeloma cells most strongly correlates with myeloma drug responses across all proteins and drugs. Unconnected nodes in the network are not shown for simplicity. Node color represents the Spearmanās rank correlation with bortezomib response across the discovery cohort. More details are at https://myelomics.com. b, Zoom into the network region around RPS6 and DEPTOR. Legend shows signed ālog10(P) per protein, sorted by their Spearmanās rank correlation coefficients. No adjustments for multiple comparisons were made. c, Box-plots (as in Fig. 2c) showing RPS6 abundance as a function of bortezomib sensitivity (nā=ā76 patient samples). d, Box-plots (as in Fig. 2c) showing DEPTOR abundance as a function of bortezomib sensitivity (nā=ā53 patient samples). e, Zoom into the network region around EYA3. f, Box-plots (as in Fig. 2c) showing EYA3 abundance as a function of bortezomib sensitivity (nā=ā51 patient samples). g, Box-plots showing the percentage of Ī³H2AX-positive myeloma cells after 24āh of DMSO or bortezomib treatment across six newly diagnosed myeloma samples (nā=ā6 patient samples). Box-plots as in Fig. 2c. P values shown are from a two-tailed paired Studentās t-test. h, STRING-db interaction network colored by their elotuzumab drug response associations, as in a. i, Zoom into the network region around HLA-DRB5. j, Box-plots (as in Fig. 2c) showing HLA-DRB5 abundance as a function of elotuzumab sensitivity (nā=ā41 patient samples). k, Box-plots (as in Fig. 2c) showing the elotuzumab-induced activated T cell interactions with myeloma cells as a function of HLA-DRB5 abundance (nā=ā40 patient samples). Example images on the right of the plot show an activated T cell with close contact to a myeloma cell (top) and a conventional T cell without cellācell contact to a myeloma cell (bottom). Scale bar, 10āĪ¼m. All P values depicted on box-plots (c,d,f,g,j,k) are from unpaired two-tailed Studentās t-tests. The tests were not adjusted for multiple comparisons. All box-plots (c,d,f,g,j,k) as in Fig. 2c.
