Design and Analysis of CRISPR Gene Editing Tests Focused on Specific Genome Areas Using FRACTEL

FRACTEL demonstrates improved power and replication rate in region-level analysis of CRISPR perturbation screens compared to gRNA-level analyses.

• FRACTEL aggregates gRNA p-values using a bounded minimum approach.
• The framework preserves scale and adapts sensitivity to varying effect sizes.
• Type I error control is achieved through simulation-based estimation of null distributions.
• Simulations and real datasets indicate enhanced performance over traditional analyses.
• FRACTEL aids in experimental design by highlighting gRNA redundancy and efficacy trade-offs.
• The method identifies limitations in single-cell repression screens for lowly expressed genes.

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