JACKS: joint analysis of CRISPR/Cas9 knockout screens.


Journal

Genome research
ISSN: 1549-5469
Titre abrégé: Genome Res
Pays: United States
ID NLM: 9518021

Informations de publication

Date de publication:
03 2019
Historique:
received: 27 04 2018
accepted: 16 01 2019
pubmed: 25 1 2019
medline: 14 6 2019
entrez: 25 1 2019
Statut: ppublish

Résumé

Genome-wide CRISPR/Cas9 knockout screens are revolutionizing mammalian functional genomics. However, their range of applications remains limited by signal variability from different guide RNAs that target the same gene, which confounds gene effect estimation and dictates large experiment sizes. To address this problem, we report JACKS, a Bayesian method that jointly analyzes screens performed with the same guide RNA library. Modeling the variable guide efficacies greatly improves hit identification over processing a single screen at a time and outperforms existing methods. This more efficient analysis gives additional hits and allows designing libraries with a 2.5-fold reduction in required cell numbers without sacrificing performance compared to current analysis standards.

Identifiants

pubmed: 30674557
pii: gr.238923.118
doi: 10.1101/gr.238923.118
pmc: PMC6396427
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

464-471

Subventions

Organisme : Wellcome Trust
Pays : United Kingdom

Informations de copyright

© 2019 Allen et al.; Published by Cold Spring Harbor Laboratory Press.

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Auteurs

Felicity Allen (F)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, United Kingdom.

Fiona Behan (F)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, United Kingdom.

Anton Khodak (A)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, United Kingdom.

Francesco Iorio (F)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, United Kingdom.

Kosuke Yusa (K)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, United Kingdom.

Mathew Garnett (M)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, United Kingdom.

Leopold Parts (L)

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, United Kingdom.
Department of Computer Science, University of Tartu, Tartu 50409, Estonia.

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Classifications MeSH