Fig. 1. Overview and SLIdR workflow.
a Definition of a synthetic lethal pair: Aberration of gene A (driver gene) or knockdown of gene B (SL partner gene) alone does not affect the viability of the cell. However, the combination of mutated gene A and knockdown of gene B is lethal to the cell. b Distribution of the number of cell lines with copy number data from CCLE across 23 different cancer types used in this study. Since most cancers have small sample sizes, the figure indicates the necessity of developing a computational tool with sufficient statistical power on small sample size data. c Illustration of the SLIdR algorithm with a toy example. The data consists of driver genes DG 1-DG 4 and perturbed genes PG 1-PG 15 across cell lines CL 1-CL 10. Cell lines CL 2-5 are mutated in the driver gene DG 1 (Mut), while the remaining cell lines are DG 1 wild-type (WT). Comparison of viability distributions across all perturbed genes PG 1-PG 15 in the DG 1 mutated (Mut) and WT cell lines shows that perturbation of gene 8 (PG 8) results in reduced viability only in CL 2-5 and not the WT cell lines. Thus, PG 8 is a SL partner of DG 1. d The computational pipeline illustrating the different steps performed to obtain the candidate SL pairs from mutation profiles and perturbation screen data.