gwaybio
commented
3 years ago We can also calculate grit at the single cell level (scGrit).
This could have some pretty nifty applications. For example in broadinstitute/grit-benchmark#4, I applied grit to a perturb-seq dataset (specifically, from GEO accession GSE132080).
Jost M, Santos DA, Saunders RA, Horlbeck MA et al. Titrating gene expression using libraries of systematically attenuated CRISPR guide RNAs. Nat Biotechnol 2020 Mar;38(3):355-364. PMID: 31932729
A compelling example of scGrit is shown below:
This is compelling b/c we know that CRISPR will not work in every single cell. This is the "CRISPR penetrance" issue. Perhaps we can use grit to filter cells before making profiles.
shntnu
(Stubs for now, so we can add this documentation to code later)
Grit can be computed in many different contexts:
A replicate's grit is its average similarity to other replicates, z-scored against its similarity to negative control replicates.
A guide's grit is its average similarity to other guides targeting the same gene, z-scored against its similarity to negative control guides.
A compound's grit (in the context of MOA) is its average similarity to other compounds in the same MOA class, z-scored against its similarity to DMSO replicates.