Fig. 1.

Screening data show an asymmetric distribution of gRNA abundance fold changes. a Screen setup for measurement of gRNA effect on cell fitness. b–d KBM7 screen [1] with highlight on non-targeting controls. e–g HCT116 screen [2] with highlight on gRNAs targeting non-essential genes (defined according to Hart et al. [25]). b, e gRNA abundance at T1 compared to T0 for one of the replicates (R1). Non-targeting control gRNAs (b) and gRNAs targeting non-essential genes (e) are shown by large symbols, all other gRNAs as small grey points. LFC: logarithm of base 2 of inverted before/after ratio calculated as -log2((normalized count at T0 + 1)/(normalized count at T1 + 1)). Colors indicate LFC <−1 (pink) and LFC > + 1 (green). c, f Fraction of non-targeting gRNAs (c) or gRNAs targeting non-essential genes (f) with LFC 1 (pink) and LFC > + 1 (green). The gRNAs were sorted according to their abundance at T0, and the frequencies were calculated within each quintile of the abundance distribution (mean over two replicates). d, g Comparison of observed LFC for two replicates R1 and R2. Colors correspond to LFC in replicate R1 as in panels b and e