Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions

We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual-guide RNAs in three cell lines, altogether comprising 141,912 tests of interaction. Numerous t...

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Detalles Bibliográficos
Autores principales: Shen, John Paul, Zhao, Dongxin, Sasik, Roman, Luebeck, Jens, Birmingham, Amanda, Bojorquez-Gomez, Ana, Licon, Katherine, Klepper, Kristin, Pekin, Daniel, Beckett, Alex, Sanchez, Kyle, Thomas, Alex, Kuo, Chih-Chung, Du, Dan, Roguev, Assen, Lewis, Nathan E., Chang, Aaron N., Kreisberg, Jason F., Krogan, Nevan, Qi, Lei, Ideker, Trey, Mali, Prashant
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449203/
https://www.ncbi.nlm.nih.gov/pubmed/28319113
http://dx.doi.org/10.1038/nmeth.4225
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author Shen, John Paul
Zhao, Dongxin
Sasik, Roman
Luebeck, Jens
Birmingham, Amanda
Bojorquez-Gomez, Ana
Licon, Katherine
Klepper, Kristin
Pekin, Daniel
Beckett, Alex
Sanchez, Kyle
Thomas, Alex
Kuo, Chih-Chung
Du, Dan
Roguev, Assen
Lewis, Nathan E.
Chang, Aaron N.
Kreisberg, Jason F.
Krogan, Nevan
Qi, Lei
Ideker, Trey
Mali, Prashant
author_facet Shen, John Paul
Zhao, Dongxin
Sasik, Roman
Luebeck, Jens
Birmingham, Amanda
Bojorquez-Gomez, Ana
Licon, Katherine
Klepper, Kristin
Pekin, Daniel
Beckett, Alex
Sanchez, Kyle
Thomas, Alex
Kuo, Chih-Chung
Du, Dan
Roguev, Assen
Lewis, Nathan E.
Chang, Aaron N.
Kreisberg, Jason F.
Krogan, Nevan
Qi, Lei
Ideker, Trey
Mali, Prashant
author_sort Shen, John Paul
collection PubMed
description We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual-guide RNAs in three cell lines, altogether comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified and these patterns replicated with combinatorial drugs at 75% precision. Based on these results we anticipate cellular context will be critical to synthetic-lethal therapies.
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spelling pubmed-54492032017-09-20 Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions Shen, John Paul Zhao, Dongxin Sasik, Roman Luebeck, Jens Birmingham, Amanda Bojorquez-Gomez, Ana Licon, Katherine Klepper, Kristin Pekin, Daniel Beckett, Alex Sanchez, Kyle Thomas, Alex Kuo, Chih-Chung Du, Dan Roguev, Assen Lewis, Nathan E. Chang, Aaron N. Kreisberg, Jason F. Krogan, Nevan Qi, Lei Ideker, Trey Mali, Prashant Nat Methods Article We developed a systematic approach to map human genetic networks by combinatorial CRISPR-Cas9 perturbations coupled to robust analysis of growth kinetics. We targeted all pairs of 73 cancer genes with dual-guide RNAs in three cell lines, altogether comprising 141,912 tests of interaction. Numerous therapeutically relevant interactions were identified and these patterns replicated with combinatorial drugs at 75% precision. Based on these results we anticipate cellular context will be critical to synthetic-lethal therapies. 2017-03-20 2017-06 /pmc/articles/PMC5449203/ /pubmed/28319113 http://dx.doi.org/10.1038/nmeth.4225 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Shen, John Paul
Zhao, Dongxin
Sasik, Roman
Luebeck, Jens
Birmingham, Amanda
Bojorquez-Gomez, Ana
Licon, Katherine
Klepper, Kristin
Pekin, Daniel
Beckett, Alex
Sanchez, Kyle
Thomas, Alex
Kuo, Chih-Chung
Du, Dan
Roguev, Assen
Lewis, Nathan E.
Chang, Aaron N.
Kreisberg, Jason F.
Krogan, Nevan
Qi, Lei
Ideker, Trey
Mali, Prashant
Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions
title Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions
title_full Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions
title_fullStr Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions
title_full_unstemmed Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions
title_short Combinatorial CRISPR-Cas9 screens for de novo mapping of genetic interactions
title_sort combinatorial crispr-cas9 screens for de novo mapping of genetic interactions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5449203/
https://www.ncbi.nlm.nih.gov/pubmed/28319113
http://dx.doi.org/10.1038/nmeth.4225
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