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Genome Biol DOI:10.1186/s13059-021-02540-7

Chronos: a cell population dynamics model of CRISPR experiments that improves inference of gene fitness effects.

Publication TypeJournal Article
Year of Publication2021
AuthorsDempster, JM, Boyle, I, Vazquez, F, Root, DE, Boehm, JS, Hahn, WC, Tsherniak, A, McFarland, JM
JournalGenome Biol
Volume22
Issue1
Pages343
Date Published2021 12 20
ISSN1474-760X
Abstract

CRISPR loss of function screens are powerful tools to interrogate biology but exhibit a number of biases and artifacts that can confound the results. Here, we introduce Chronos, an algorithm for inferring gene knockout fitness effects based on an explicit model of cell proliferation dynamics after CRISPR gene knockout. We test Chronos on two pan-cancer CRISPR datasets and one longitudinal CRISPR screen. Chronos generally outperforms competitors in separation of controls and strength of biomarker associations, particularly when longitudinal data is available. Additionally, Chronos exhibits the lowest copy number and screen quality bias of evaluated methods. Chronos is available at https://github.com/broadinstitute/chronos .

DOI10.1186/s13059-021-02540-7
Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/34930405?dopt=Abstract

Alternate JournalGenome Biol
PubMed ID34930405
PubMed Central IDPMC8686573