Extended Data Fig. 2: HCR-FlowFISH screens display high similarity and increased sensitivity compared to growth screens at the GATA1 locus.

a, Overlap of the GATA1 guide library used in this study and Fulco et al.17 library. b, High correlation (Pearson r = 0.84, two-sided t-test P = 3.4 × 10−106) between individual guide scores for detected sgRNAs shared in the GATA1 HCR-FlowFISH screen and the Fulco et al.17 growth screen (black line is the ordinary least squares regression best fit, gray shaded band is 95% confidence interval). c, Guide-wise score comparison for all sgRNAs shared between growth and HCR-FlowFISH screens, showing read-depth of gRNA drives correlation more than off-target effects (cutting specificity). d, Individual gRNA guide scores plotted at the GATA1 promoter locus display the opposite direction CREs for GATA1 and HDAC6. e, Comparison of individual guide scores for guides shared between the HCR-FlowFISH and Fulco et al.17 growth screens. The distributions scores within CREs are more distinctly separated from those without when using HCR-FlowFISH. The minima, centers, and maxima of the boxes indicate the 25th, 50th, and 75th percentiles of the data distributions. Whiskers capture all remaining data, excluding outliers extending beyond 1.5 times the interquartile range below or above the 25th or 75th percentiles, respectively. n = 906 (grey boxes) and n = 313 (green boxes) shared guides analyzed outside and inside CRE boundaries, respectively.