Hi I am curious to understand if guide RNA mediated edits are typically het/hom deletions in the Achilles screen? Or a mixture of both? In other words, does the gene dependency probability refer to complete absence of the particular gene or could it also be heterozygous deletion?
Presumably it’s some distribution over the possible range of editing outcomes, but we don’t know exactly what that distribution is. Achilles does not include any measure of the actual genomic alteration other than the viability phenotype we observe. For any particular guide we have to assume that its infected cells have an unknown mix of heterozygous LOF, homozygous LOF, and conserved function. To help mitigate this source of noise, dependency probability is always calculated from a summary measure of viability over multiple guides.