A map of directional genetic interactions in a metazoan cell
Gene–gene interactions shape complex phenotypes and modify the effects of mutations during development and disease. The effects of statistical gene–gene interactions on phenotypes have been used to assign genes to functional modules. However, directional, epistatic interactions, which reflect regula...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2015-03-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/05464 |
| _version_ | 1811180451754147840 |
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| author | Bernd Fischer Thomas Sandmann Thomas Horn Maximilian Billmann Varun Chaudhary Wolfgang Huber Michael Boutros |
| author_facet | Bernd Fischer Thomas Sandmann Thomas Horn Maximilian Billmann Varun Chaudhary Wolfgang Huber Michael Boutros |
| author_sort | Bernd Fischer |
| collection | DOAJ |
| description | Gene–gene interactions shape complex phenotypes and modify the effects of mutations during development and disease. The effects of statistical gene–gene interactions on phenotypes have been used to assign genes to functional modules. However, directional, epistatic interactions, which reflect regulatory relationships between genes, have been challenging to map at large-scale. Here, we used combinatorial RNA interference and automated single-cell phenotyping to generate a large genetic interaction map for 21 phenotypic features of Drosophila cells. We devised a method that combines genetic interactions on multiple phenotypes to reveal directional relationships. This network reconstructed the sequence of protein activities in mitosis. Moreover, it revealed that the Ras pathway interacts with the SWI/SNF chromatin-remodelling complex, an interaction that we show is conserved in human cancer cells. Our study presents a powerful approach for reconstructing directional regulatory networks and provides a resource for the interpretation of functional consequences of genetic alterations. |
| first_indexed | 2024-04-11T09:02:21Z |
| format | Article |
| id | doaj.art-041f5fa32d464532bec0192fb7eb5ee0 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:02:21Z |
| publishDate | 2015-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-041f5fa32d464532bec0192fb7eb5ee02022-12-22T04:32:43ZengeLife Sciences Publications LtdeLife2050-084X2015-03-01410.7554/eLife.05464A map of directional genetic interactions in a metazoan cellBernd Fischer0https://orcid.org/0000-0001-9437-2099Thomas Sandmann1Thomas Horn2Maximilian Billmann3Varun Chaudhary4Wolfgang Huber5Michael Boutros6Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, GermanyDivision of Signaling and Functional Genomics, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Cell and Molecular Biology, Faculty of Medicine Mannheim, Heidelberg University, Heidelberg, GermanyDivision of Signaling and Functional Genomics, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Cell and Molecular Biology, Faculty of Medicine Mannheim, Heidelberg University, Heidelberg, GermanyDivision of Signaling and Functional Genomics, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Cell and Molecular Biology, Faculty of Medicine Mannheim, Heidelberg University, Heidelberg, GermanyDivision of Signaling and Functional Genomics, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Cell and Molecular Biology, Faculty of Medicine Mannheim, Heidelberg University, Heidelberg, GermanyGenome Biology Unit, European Molecular Biology Laboratory, Heidelberg, GermanyDivision of Signaling and Functional Genomics, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Cell and Molecular Biology, Faculty of Medicine Mannheim, Heidelberg University, Heidelberg, GermanyGene–gene interactions shape complex phenotypes and modify the effects of mutations during development and disease. The effects of statistical gene–gene interactions on phenotypes have been used to assign genes to functional modules. However, directional, epistatic interactions, which reflect regulatory relationships between genes, have been challenging to map at large-scale. Here, we used combinatorial RNA interference and automated single-cell phenotyping to generate a large genetic interaction map for 21 phenotypic features of Drosophila cells. We devised a method that combines genetic interactions on multiple phenotypes to reveal directional relationships. This network reconstructed the sequence of protein activities in mitosis. Moreover, it revealed that the Ras pathway interacts with the SWI/SNF chromatin-remodelling complex, an interaction that we show is conserved in human cancer cells. Our study presents a powerful approach for reconstructing directional regulatory networks and provides a resource for the interpretation of functional consequences of genetic alterations.https://elifesciences.org/articles/05464genetic interactionepistasisimage-based phenotyping |
| spellingShingle | Bernd Fischer Thomas Sandmann Thomas Horn Maximilian Billmann Varun Chaudhary Wolfgang Huber Michael Boutros A map of directional genetic interactions in a metazoan cell eLife genetic interaction epistasis image-based phenotyping |
| title | A map of directional genetic interactions in a metazoan cell |
| title_full | A map of directional genetic interactions in a metazoan cell |
| title_fullStr | A map of directional genetic interactions in a metazoan cell |
| title_full_unstemmed | A map of directional genetic interactions in a metazoan cell |
| title_short | A map of directional genetic interactions in a metazoan cell |
| title_sort | map of directional genetic interactions in a metazoan cell |
| topic | genetic interaction epistasis image-based phenotyping |
| url | https://elifesciences.org/articles/05464 |
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