Region-Level Design and Analysis of CRISPR Perturbation Screens with FRACTEL

Authors

Doty, R. W., ter Weele, M. A., Barrera, A., Bounds, L. R., Gersbach, C. A., Allen, A. S.

Abstract

We present FRACTEL, a statistical framework for region-level analysis of CRISPR perturbation screens. FRACTEL aggregates gRNA p-values using a bounded minimum across order statistics, preserving scale and enabling adaptive sensitivity to sparse or diffuse effects. Region-level null distributions are estimated via simulation, ensuring precise type I error control. Simulations and real CRISPRi/a datasets demonstrate improved power and replication rate over gRNA-level analyses. FRACTEL also informs experimental design, revealing trade-offs between gRNA redundancy and efficacy and identifying inherent limits in single-cell repression screens of lowly expressed genes. The method integrates with existing pipelines and supports diverse CRISPR screening applications.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 08 Jul 2026.

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