Dual gene activation and knockout screen reveals directional dependencies in genetic networks
| العنوان: | Dual gene activation and knockout screen reveals directional dependencies in genetic networks |
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| المؤلفون: | Ryan T. Wagner, Haian Fu, Frank McCormick, Xiulei Mo, Michael T. McManus, James Blau, Martin Kampmann, Anne Biton, Ruilin Tian, David Wu, Evan Markegard, Michael Boettcher, Noah Zaitlen |
| المصدر: | Nature Biotechnology. 36:170-178 |
| بيانات النشر: | Springer Science and Business Media LLC, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Regulation of gene expression, Cas9, Biomedical Engineering, Bioengineering, Computational biology, Biology, Applied Microbiology and Biotechnology, Phenotype, 03 medical and health sciences, 030104 developmental biology, Interaction network, Gene Knockout Techniques, Molecular Medicine, Directionality, Epistasis, Gene, Biotechnology |
| الوصف: | Understanding the direction of information flow is essential for characterizing how genetic networks affect phenotypes. However, methods to find genetic interactions largely fail to reveal directional dependencies. We combine two orthogonal Cas9 proteins from Streptococcus pyogenes and Staphylococcus aureus to carry out a dual screen in which one gene is activated while a second gene is deleted in the same cell. We analyze the quantitative effects of activation and knockout to calculate genetic interaction and directionality scores for each gene pair. Based on the results from over 100,000 perturbed gene pairs, we reconstruct a directional dependency network for human K562 leukemia cells and demonstrate how our approach allows the determination of directionality in activating genetic interactions. Our interaction network connects previously uncharacterized genes to well-studied pathways and identifies targets relevant for therapeutic intervention. |
| تدمد: | 1546-1696 1087-0156 |
| DOI: | 10.1038/nbt.4062 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::8722e8cb80bb8dfc772576a41abd7b8a https://doi.org/10.1038/nbt.4062 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi...........8722e8cb80bb8dfc772576a41abd7b8a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15461696 10870156 |
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| DOI: | 10.1038/nbt.4062 |