A one-step tRNA-CRISPR system for genome-wide genetic interaction mapping in mammalian cells

Mapping genetic interactions in mammalian cells is limited due to technical obstacles. Here we describe a method called TCGI (tRNA-CRISPR for genetic interactions) to generate a high-efficient, barcode-free and scalable pairwise CRISPR libraries in mammalian cells for identifying genetic interaction...

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Autores principales: Zhao, Yulei, Tyrishkin, Kathrin, Sjaarda, Calvin, Khanal, Prem, Stafford, Jeff, Rauh, Michael, Liu, Xudong, Babak, Tomas, Yang, Xiaolong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787096/
https://www.ncbi.nlm.nih.gov/pubmed/31601883
http://dx.doi.org/10.1038/s41598-019-51090-3
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author Zhao, Yulei
Tyrishkin, Kathrin
Sjaarda, Calvin
Khanal, Prem
Stafford, Jeff
Rauh, Michael
Liu, Xudong
Babak, Tomas
Yang, Xiaolong
author_facet Zhao, Yulei
Tyrishkin, Kathrin
Sjaarda, Calvin
Khanal, Prem
Stafford, Jeff
Rauh, Michael
Liu, Xudong
Babak, Tomas
Yang, Xiaolong
author_sort Zhao, Yulei
collection PubMed
description Mapping genetic interactions in mammalian cells is limited due to technical obstacles. Here we describe a method called TCGI (tRNA-CRISPR for genetic interactions) to generate a high-efficient, barcode-free and scalable pairwise CRISPR libraries in mammalian cells for identifying genetic interactions. We have generated a genome- wide library to identify genes genetically interacting with TAZ in cell viability regulation. Validation of candidate synergistic genes reveals the screening accuracy of 85% and TAZ-MCL1 is characterized as combinational drug targets for non-small cell lung cancer treatments. TCGI has dramatically improved the current methods for mapping genetic interactions and screening drug targets for combinational therapies.
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spelling pubmed-67870962019-10-17 A one-step tRNA-CRISPR system for genome-wide genetic interaction mapping in mammalian cells Zhao, Yulei Tyrishkin, Kathrin Sjaarda, Calvin Khanal, Prem Stafford, Jeff Rauh, Michael Liu, Xudong Babak, Tomas Yang, Xiaolong Sci Rep Article Mapping genetic interactions in mammalian cells is limited due to technical obstacles. Here we describe a method called TCGI (tRNA-CRISPR for genetic interactions) to generate a high-efficient, barcode-free and scalable pairwise CRISPR libraries in mammalian cells for identifying genetic interactions. We have generated a genome- wide library to identify genes genetically interacting with TAZ in cell viability regulation. Validation of candidate synergistic genes reveals the screening accuracy of 85% and TAZ-MCL1 is characterized as combinational drug targets for non-small cell lung cancer treatments. TCGI has dramatically improved the current methods for mapping genetic interactions and screening drug targets for combinational therapies. Nature Publishing Group UK 2019-10-10 /pmc/articles/PMC6787096/ /pubmed/31601883 http://dx.doi.org/10.1038/s41598-019-51090-3 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Zhao, Yulei
Tyrishkin, Kathrin
Sjaarda, Calvin
Khanal, Prem
Stafford, Jeff
Rauh, Michael
Liu, Xudong
Babak, Tomas
Yang, Xiaolong
A one-step tRNA-CRISPR system for genome-wide genetic interaction mapping in mammalian cells
title A one-step tRNA-CRISPR system for genome-wide genetic interaction mapping in mammalian cells
title_full A one-step tRNA-CRISPR system for genome-wide genetic interaction mapping in mammalian cells
title_fullStr A one-step tRNA-CRISPR system for genome-wide genetic interaction mapping in mammalian cells
title_full_unstemmed A one-step tRNA-CRISPR system for genome-wide genetic interaction mapping in mammalian cells
title_short A one-step tRNA-CRISPR system for genome-wide genetic interaction mapping in mammalian cells
title_sort one-step trna-crispr system for genome-wide genetic interaction mapping in mammalian cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787096/
https://www.ncbi.nlm.nih.gov/pubmed/31601883
http://dx.doi.org/10.1038/s41598-019-51090-3
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