Extended Data Fig. 5. Comparisons with independent CRISPR-Cas13a datasets.

a, Each point is a guide-target pair from experiments in ref. ³⁷ measuring LbuCas13a nuclease activity. Horizontal axis is the measured, normalized percent cleavage rate relative to no mismatches and dashed line at 100 shows the value for no mismatches. Vertical axis is our model’s predicted LwaCas13a collateral cleavage activity. Colors indicate the number of mismatches in the guide-target pair. ρ, Spearman correlation; r, Pearson correlation coefficient. b, Same as a, but only for points where mismatches decrease the LbuCas13a cleavage rate—that is, points to the left of the dashed line. Considering this subset helps to mitigate differences arising from LbuCas13a’s higher overall collateral activity compared to LwaCas13a. c, Each point is a guide-target pair from experiments in ref. ³⁷ measuring LbuCas13a–RNA binding affinity. Horizontal axis is the measured, regularized fold-change enrichment for binding to a target. Vertical axis is our model’s predicted LwaCas13a collateral cleavage activity. d, Same as c, but only for points where mismatches decrease the binding affinity compared to no mismatches. e, Same data as c. Each row contains one quartile of pairs divided by our model’s predicted activity (top row, 4, is predicted most active). Colors in each bar indicate the fraction of pairs belonging to each quartile of the binding affinity measurements (4 is highest binding). f, Same data as c. Each row contains one quartile of pairs divided by binding affinity measurements (top row, 4, is highest binding). Colors in each bar indicate the fraction of pairs belonging to each quartile of the predicted activities (4 is predicted most active). We do not expect a high correlation in c–f owing to differences between the variables being compared and between LbuCas13a and LwaCas13a; nevertheless, the relationship is consistent with binding being necessary, though not sufficient, to achieve collateral activity. g, Each point is a guide-target pair from experiments in ref. ³⁶ measuring knockdown levels from LwaCas13a on-target cis cleavage. Horizontal axis is the measured knockdown level. In the normalized measurements, the non-targeting guide was set to a knockdown level of 1. Vertical axis is our model’s predicted LwaCas13a activity.