REN and cancer: We also spiked in a panel of 41 negative control sgRNAs (targeting nonhuman genes such as Luc, LacZ, Ren and Rosa26 and scrambled sequences) and 27 positive control sgRNAs (targeting cancer-essential genes such as MYC, PCNA and RPA3) (Extended Data Fig. 1a,b and Supplementary Table 2).