A genome-wide CRISPR screen tests every gene in the genome for its effect on a phenotype simultaneously, then relies on statistics — not prior biological hypotheses — to separate real hit genes from the inevitable background noise.
hit if |phenotypeScore_gene| > stringency * background_sd
- Gene nodes screened — every gene in the genome-wide library, each independently knocked out across the cell pool.
- Guide coverage per gene — how many independent guide RNAs target each gene — more guides means more confidence in a hit.
- Phenotypic signal strength — how strongly a true target gene's knockout actually shifts the measured phenotype.
- Hit-calling stringency — the statistical threshold separating a real hit from background noise across thousands of genes tested at once.
Genome-wide CRISPR screens identified SLFN11 as a predictive biomarker for DNA-damaging chemotherapy response and uncovered whole new classes of synthetic-lethal cancer targets that candidate-gene studies had missed for decades.