Figure 3.

Schematic demonstrating how Orthrus accounts for guide orientation during combinatorial scoring by scoring guides from different orientations separately. Orientation is represented as guides that occupy different positions along a guide construct that targets both gene A and gene B. For both orientations, combinatorial knockouts are compared to expected effects derived from the sum of matching single knockout LFCs. After hypothesis testing, filters for absolute value of effect size, FDR and whether or not both orientations’ effects have the same effect sign are applied to call significant hits.