Red: stable co-clustering Blue: no co-clustering Supplementary Figure 1 Red: stable co-clustering Blue: no co-clustering 2-cluster 3-cluster Results of NMF in 74 samples from the WG dataset These plots show how often each pair of samples (74x74 pairings) were in the same cluster during 20 iterations of NMF. Dark red means the samples were always in the same cluster and dark blue means they never were. There is support for 2, 3, and 4 stable cluster assignments by NMF. K5 and K6 are unstable. 4-cluster 5-cluster

Supplementary Figure 2

Supplementary Figure 3

Supplementary Figure 4 P=0.16 EGFR mutation

Supplementary Figure 5

Supplementary Figure 6 EGFR mutation KRAS mutation

26 10 16 14 5 7 17 104 n=199 DUSP4 deletion p16 deletion EGFR mutation Supplementary Figure 7 p=0.0001 DUSP4 deletion p16 deletion 26 10 16 14 5 7 p=0.00003 p=0.007 17 104 EGFR mutation n=199

Wild type EGFR EGFR del19 EGFR L858R Supplementary Figure 8 6E-16 Wild type EGFR EGFR del19 EGFR L858R 5E-16 4E-16 DUSP4 mRNA conc (uM) 3E-16 2E-16 1E-16 WT - No EGF WT - 2 hrs WT - 4 hrs WT - 30 min WT - 1 hr WT - 6 hrs del19 - No EGF del19 - 30 min del19 - 2 hrs del19 - 4 hrs del19 - 6 hrs L858R - No EGF del19 - 1 hr L858R - 30 min L858R - 2 hrs L858R - 4 hrs L858R - 1 hr L858R - 6 hrs

Supplementary Figure 9 A B GFP DUSP4-GFP H358 H1650 H1650 DUSP4 Vector 70KD DUSP4-GFP 27KD GFP ACTIN H358 H1650 H1650

Supplementary Figure 10 H1650 cells 24hrs after electroporation H1650 cells after one week selection GFP DUSP4-GFP