Reproducibility metrics for context-specific CRISPR screens

Maximilian Billmann; Henry N Ward; Michael Aregger; Michael Costanzo; Brenda J Andrews; Charles Boone; Jason Moffat; Chad L Myers

doi:10.1016/j.cels.2023.04.003

Reproducibility metrics for context-specific CRISPR screens

Cell Syst. 2023 May 17;14(5):418-422.e2. doi: 10.1016/j.cels.2023.04.003.

Authors

Maximilian Billmann¹, Henry N Ward², Michael Aregger³, Michael Costanzo⁴, Brenda J Andrews⁵, Charles Boone⁵, Jason Moffat⁶, Chad L Myers⁷

Affiliations

¹ Department of Computer Science and Engineering, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA; Institute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn 53127, Germany. Electronic address: maximilian.billmann@gmail.com.
² Bioinformatics and Computational Biology Graduate Program, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA.
³ National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA; Donnelly Centre, University of Toronto, Toronto, ON M5S3E1, Canada.
⁴ Donnelly Centre, University of Toronto, Toronto, ON M5S3E1, Canada.
⁵ Donnelly Centre, University of Toronto, Toronto, ON M5S3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S1A8, Canada.
⁶ Donnelly Centre, University of Toronto, Toronto, ON M5S3E1, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S1A8, Canada; Program in Genetics and Genome Biology, The Hospital for Sick Children, Peter Gilgan Research and Learning Centre, 686 Bay Street, Toronto, ON M5G0A4, Canada.
⁷ Department of Computer Science and Engineering, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA; Bioinformatics and Computational Biology Graduate Program, University of Minnesota, Twin Cities, Minneapolis, MN 55455, USA. Electronic address: chadm@umn.edu.

PMID: 37201508
PMCID: PMC10266068 (available on 2024-05-17)
DOI: 10.1016/j.cels.2023.04.003

Abstract

CRISPR screens are used extensively to systematically interrogate the phenotype-to-genotype problem. In contrast to early CRISPR screens, which defined core cell fitness genes, most current efforts now aim to identify context-specific phenotypes that differentiate a cell line, genetic background, or condition of interest, such as a drug treatment. While CRISPR-related technologies have shown great promise and a fast pace of innovation, a better understanding of standards and methods for quality assessment of CRISPR screen results is crucial to guide technology development and application. Specifically, many commonly used metrics for quantifying screen quality do not accurately measure the reproducibility of context-specific hits. We highlight the importance of reporting reproducibility statistics that directly relate to the purpose of the screen and suggest the use of metrics that are sensitive to context-specific signal. A record of this paper's transparent peer review process is included in the supplemental information.

Keywords: CRISPR screening; correlation coefficients; genetic interactions; replicate correlation; reproducibility.

Reproducibility metrics for context-specific CRISPR screens

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