Extended Data Fig. 7: C11orf53/OCA-T1 and COLCA2/OCA-T2 are selective dependencies in SCLC-P lines.

(a) Two-class comparison of gene dependencies of four SCLC-P versus 986 other cancer cell lines. The average essentiality of each gene from SCLC-P is subtracted to its mean in other cell lines. This difference is moderated with an empirical Bayes method using the adaptive shrinkage method described in CRNA package - ashr. (b) Scatter plot of C11orf53, COLCA2, and POU2F3 dependency scores across a panel of human cancer cell lines. Data obtained from DepMap (21Q2). (c) Control sgRNAs (2 negative controls or one sgCDK1) for the competition-based proliferation assays (related to Fig. 4a), (n = 3). Mean ± s.d. is plotted. (d) BrdU incorporation assays following CRISPR-based targeting of POU2F3, C11orf53, or COLCA2 or negative control in the indicated Cas9⁺ cell lines. Two technical replicates with two independent sgRNAs for each gene as biological replicates. Adjusted P value was calculated with two-way ANOVA with Tukey’s multiple comparison tests. (e-f) Tumour weights and imaging at the terminal timepoint of the xenograft experiments shown in Fig. 4b. Mean ± s.e.m. is plotted for (d-e). P-values are derived from two-tailed unpaired student’s t-test with Welch’s correction. (g) Controls for NCI-H211 gene complementation assay shown in Fig. 4c. (n = 3). Mean ± s.d. is plotted. (h) Competition-based proliferation assays in NCI-H1048 cells cotransduced with indicated cDNAs and sgRNAs lentivirally to assess functionality of indicated mutants. cDNAs were engineered to be resistant to Cas9/sgRNA-mediated cutting. Mean ± s.d. of normalized GFP percentage is plotted (n = 3). (i) anti-HA western blot of the indicated cDNAs from (h). Data are representative of two biological replicates. Source data for all GFP depletion assays, BrdU assays and tumour weights are provided in Supplementary Table 3-4, gating strategy for BrdU assay is provided in Supplementary Figure 2, sgRNA sequences are provided in Supplementary Table 4, uncropped gels are provided in Supplementary Fig. 1j.