Figure 4.
Synthetic lethal Big Papi screen. (a) Correlation between measured and expected log2-fold-change values for combinatorial targeting. Data points above (red) and below (blue) 2 standard deviations are highlighted, representing buffering and synthetic lethal interactions, respectively. Data from Meljuso cells are plotted as a representative cell line. (b) Distribution of all false discovery rates determined for buffering and synthetic lethal interactions using either data from individual cell lines (1 line) or combining data from 5 lines. When 5 lines are combined, more pairs score with either low FDRs or with an FDR = 1. (c) FDRs for synthetic lethal interactions for gene pairs within pre-defined groups at the day 21 time point. Results are shown from individual cell lines, all leave-one-out combinations, and the combination of all 6 lines. (d) Primary screening data showing the performance of sgRNAs for BCL2L1 and MCL1 when paired together or with 6T controls in Meljuso cells at day 21. Average is denoted with a line whereas each dot represents an sgRNA combination. Dotted line refers to 2 standard deviations (2SD) from the mean for individual sgRNAs paired with controls (black dots). P-values for depletion of the dual-targeting sets of sgRNA pairs are based on the Mann-Whitney test, **P<0.01; ***P<0.001; ****P<0.0001. (e) Comparisons of the estimated true positive rate to the calculated FDR for synthetic lethal and buffering interactions, using either individual cell lines or all leave-one-out combinations of 5 cell lines. (f) Estimation of the false negative rate based on analysis of same-gene buffering interactions, using either individual cell lines or all leave-one-out combinations of 5 cell lines, plotted against the FDR.