Z-Scores Outperform Similar Methods for Analyzing CRISPR Paralog Synthetic Lethality Screens

Authors

Juihsuan Chou
Nazanin Esmaeili Anvar
Reem Elghaish
Junjie Chen
Traver Hart

Publication Date

7-2-2025

Journal

Genome Biology

DOI

10.1186/s13059-025-03660-0

PMID

40605002

PMCID

PMC12217507

PubMedCentral® Posted Date

7-2-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Genetic screens offer a promising strategy for identifying tumor-specific therapeutic targets, but single-gene knockout screens often miss functionally redundant paralogs. Multiplex Cas9 and Cas12a CRISPR systems have been deployed to assay genetic interactions, but analysis pipelines vary considerably. Here we evaluate data from four in4mer CRISPR/Cas12a screens in cancer cell lines, using delta log fold change, Z-transformed dLFC, and rescaled dLFC approaches to identify synthetic lethal interactions. Both ZdLFC and RdLFC provide more consistent identification of synthetic lethal pairs across cell lines compared to the unscaled dLFC method, while ZdLFC benefits from not requiring a training set of known interactors.

Keywords

Humans, CRISPR-Cas Systems, Synthetic Lethal Mutations, Cell Line, Tumor

Published Open-Access

yes

Recommended Citation

Chou, Juihsuan; Esmaeili Anvar, Nazanin; Elghaish, Reem; et al., "Z-Scores Outperform Similar Methods for Analyzing CRISPR Paralog Synthetic Lethality Screens" (2025). Faculty, Staff and Student Publications. 4299.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/4299