MAGeCK enables robust identification of essential  genes from genome-scale CRISPR/Cas9 knockout  screens

Wei Li; Han Xu; Tengfei Xiao; Le Cong; Michael I. Love; Feng Zhang; Rafael A. Irizarry; Jun S. Liu; Myles Brown; X. Shirley Liu

doi:10.1186/s13059-014-0554-4

MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens

Wei Li, Han Xu, Tengfei Xiao, Le Cong, Michael I. Love, Feng Zhang, Rafael A. Irizarry, Jun S. Liu, Myles Brown, X. Shirley Liu

Research output: Contribution to journal › Article › peer-review

1169 Scopus citations

Abstract

We propose the Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout (MAGeCK) method for prioritizing single-guide RNAs, genes and pathways in genome-scale CRISPR/Cas9 knockout screens. MAGeCK demonstrates better performance compared with existing methods, identifies both positively and negatively selected genes simultaneously, and reports robust results across different experimental conditions. Using public datasets, MAGeCK identified novel essential genes and pathways, including EGFR in vemurafenib-treated A375 cells harboring a BRAF mutation. MAGeCK also detected cell type-specific essential genes, including BCR and ABL1, in KBM7 cells bearing a BCR-ABL fusion, and IGF1R in HL-60 cells, which depends on the insulin signaling pathway for proliferation.

Original language	English (US)
Article number	554
Pages (from-to)	554
Number of pages	1
Journal	Genome biology
Volume	15
Issue number	12
DOIs	https://doi.org/10.1186/s13059-014-0554-4
State	Published - 2014
Externally published	Yes

ASJC Scopus subject areas

Ecology, Evolution, Behavior and Systematics
Genetics
Cell Biology

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title = "MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens",

abstract = "We propose the Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout (MAGeCK) method for prioritizing single-guide RNAs, genes and pathways in genome-scale CRISPR/Cas9 knockout screens. MAGeCK demonstrates better performance compared with existing methods, identifies both positively and negatively selected genes simultaneously, and reports robust results across different experimental conditions. Using public datasets, MAGeCK identified novel essential genes and pathways, including EGFR in vemurafenib-treated A375 cells harboring a BRAF mutation. MAGeCK also detected cell type-specific essential genes, including BCR and ABL1, in KBM7 cells bearing a BCR-ABL fusion, and IGF1R in HL-60 cells, which depends on the insulin signaling pathway for proliferation.",

author = "Wei Li and Han Xu and Tengfei Xiao and Le Cong and Love, {Michael I.} and Feng Zhang and Irizarry, {Rafael A.} and Liu, {Jun S.} and Myles Brown and Liu, {X. Shirley}",

note = "Funding Information: The authors would like to thank Drs Tim Wang, Eric Lander, David Sabatini, Ophir Shalem, Neville Sanjana, Graham McVicker and Clifford Meyer for providing the datasets and helpful discussions. This project was supported by the NIH R01 GM099409 (to XSL), and the Claudia Adams Barr Award in Innovative Basic Cancer Research from the Dana-Farber Cancer Institute.",

year = "2014",

doi = "10.1186/s13059-014-0554-4",

language = "English (US)",

volume = "15",

pages = "554",

journal = "Genome biology",

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AU - Li, Wei

AU - Xu, Han

AU - Xiao, Tengfei

AU - Cong, Le

AU - Love, Michael I.

AU - Zhang, Feng

AU - Irizarry, Rafael A.

AU - Liu, Jun S.

AU - Brown, Myles

AU - Liu, X. Shirley

N1 - Funding Information: The authors would like to thank Drs Tim Wang, Eric Lander, David Sabatini, Ophir Shalem, Neville Sanjana, Graham McVicker and Clifford Meyer for providing the datasets and helpful discussions. This project was supported by the NIH R01 GM099409 (to XSL), and the Claudia Adams Barr Award in Innovative Basic Cancer Research from the Dana-Farber Cancer Institute.

PY - 2014

Y1 - 2014

N2 - We propose the Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout (MAGeCK) method for prioritizing single-guide RNAs, genes and pathways in genome-scale CRISPR/Cas9 knockout screens. MAGeCK demonstrates better performance compared with existing methods, identifies both positively and negatively selected genes simultaneously, and reports robust results across different experimental conditions. Using public datasets, MAGeCK identified novel essential genes and pathways, including EGFR in vemurafenib-treated A375 cells harboring a BRAF mutation. MAGeCK also detected cell type-specific essential genes, including BCR and ABL1, in KBM7 cells bearing a BCR-ABL fusion, and IGF1R in HL-60 cells, which depends on the insulin signaling pathway for proliferation.

AB - We propose the Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout (MAGeCK) method for prioritizing single-guide RNAs, genes and pathways in genome-scale CRISPR/Cas9 knockout screens. MAGeCK demonstrates better performance compared with existing methods, identifies both positively and negatively selected genes simultaneously, and reports robust results across different experimental conditions. Using public datasets, MAGeCK identified novel essential genes and pathways, including EGFR in vemurafenib-treated A375 cells harboring a BRAF mutation. MAGeCK also detected cell type-specific essential genes, including BCR and ABL1, in KBM7 cells bearing a BCR-ABL fusion, and IGF1R in HL-60 cells, which depends on the insulin signaling pathway for proliferation.

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MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens

Abstract

ASJC Scopus subject areas

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