Fig. 2

The interplay between multiple alignments and synthetic lethality in the Avana library. a Genomic mapping of the Avana guides targeting MYL12A and MYL12B. Guides A1 and A2 map uniquely to MYL12A and guides B1 and B2 map uniquely to MYL12B. Guides B3 and B4 map to MYL12B, but also to additional non-functional pseudogenes. Guides AB1 and AB2 map to both MYL12A and MYL12B. b Copy number-corrected LFCs for guides mapping to either MYL12A or MYL12B, or to both, in the Avana library, across 391 cell lines; each dot represents a cell line. c First panel: scatterplot of the log-fold changes between the two guides mapping to both MYL12A and MYL12B. Second and third panels: relationship between guide-specific log-fold changes and MYL9 expression for guide AB1 and AB2, respectively. d Same as b, but after adjusting for cell-specific cleavage toxicity; on-target cleavage toxicity induced by multiple on-targets was first estimated for each cell line using the fitting curves from Fig. 1f and then subtracted from each guide’s log-fold change according to their respective number of multiple on-target alignments