Protein network and pathway analyses of the 47 positively selected hits enriched for PI3K-mTOR signaling (such as PTEN, TSC1 and TSC2) and RAS-MAPK signaling (such as NF1, SPRY2 and LZTR1) pathways (Figure 1H and Figure 1—figure supplement 1G), two well-established modes of resistance to EGFR TKI in EGFR-mutant NSCLC (Pao and Chmielecki, 2010; Chong and Jänne, 2013; Niederst and Engelman, 2013; Rotow and Bivona, 2017), validating the good performance of our CRISPR screen. The gene discussed is PIK3CA; the disease is non-small cell lung carcinoma.