A statistical simulation model to guide the choices of analytical methods in arrayed CRISPR screen experiments.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2024
Historique:
received: 06 05 2024
accepted: 03 07 2024
medline: 20 8 2024
pubmed: 20 8 2024
entrez: 20 8 2024
Statut: epublish

Résumé

An arrayed CRISPR screen is a high-throughput functional genomic screening method, which typically uses 384 well plates and has different gene knockouts in different wells. Despite various computational workflows, there is currently no systematic way to find what is a good workflow for arrayed CRISPR screening data analysis. To guide this choice, we developed a statistical simulation model that mimics the data generating process of arrayed CRISPR screening experiments. Our model is flexible and can simulate effects on phenotypic readouts of various experimental factors, such as the effect size of gene editing, as well as biological and technical variations. With two examples, we showed that the simulation model can assist making principled choice of normalization and hit calling method for the arrayed CRISPR data analysis. This simulation model is implemented in an R package and can be downloaded from Github.

Identifiants

pubmed: 39163294
doi: 10.1371/journal.pone.0307445
pii: PONE-D-24-18117
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0307445

Informations de copyright

Copyright: © 2024 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

All authors are employees of AstraZeneca and has stock ownership and/or stock options or interests in the company. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Auteurs

Chang Sik Kim (CS)

Data Sciences & Quantitative Biology, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, England.

Jonathan Cairns (J)

Data Sciences & Quantitative Biology, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, England.

Valentina Quarantotti (V)

Functional Genomics, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, England.

Bogumil Kaczkowski (B)

Data Sciences & Quantitative Biology, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, England.

Yinhai Wang (Y)

Data Sciences & Quantitative Biology, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, England.

Peter Konings (P)

Data Sciences & Quantitative Biology, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, England.

Xiang Zhang (X)

Data Sciences & Quantitative Biology, Discovery Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, England.

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Classifications MeSH