Peer-Reviewed Publication
bioRxiv2026July 7, 2026Journal Article

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

Richard W Doty1,2, Maria A Ter Weele2,3, Alejandro Barrera2,3, Lexi R Bounds2,3,4, Charles A Gersbach2,3, Andrew S Allen1,2
1Department of Biostatistics & Bioinformatics, Duke University, Durham, 27705, NC, USA.
2Center for Advanced Genomic Technologies, Duke University, Durham, 27705, NC, USA.
3Department of Biomedical Engineering, Duke University, Durham, 27705, NC, USA.
4Xaira Therapeutics, South San Francisco, 94080, CA, USA.

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 dat…

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