A map of directional genetic interactions in a metazoan cell
- European Molecular Biology Laboratory, Germany
- German Cancer Research Center (DKFZ), Germany
- Heidelberg University, Germany
Figures
Figure 1 with 3 supplements
Combinatorial RNAi to map multi-phenotype genetic interactions.
(A) Workflow for multi-phenotype genetic interaction analysis by RNAi. (B) Reproducibility of phenotypic measurements. Plot shows replicate measurements for 1293 target genes at the beginning and …
Figure 1—figure supplement 1
Experimental design.
Re-analysis of the multi-parametric genetic interaction data set of Horn et al. (2010), a square matrix of all pairwise combinations of 93 genes. Matrix columns (playing the role of query genes) …
Figure 1—figure supplement 2
Selection of query genes.
Pairwise scatter plots of the first five principal components of the feature space (multivariate phenotypes) of the single-dsRNA effects against all target genes are shown. The genes selected as …
Figure 1—figure supplement 3
Comparison of phenotypes.
The measured single gene phenotypes were compared between this study and the study by Rohn et al. (2011) on the overlapping set of genes. The y-axis shows single gene phenotypes of this study. The …
Figure 2
Genetic interactions across multiple phenotypes.
(A) On top, the fraction of genetic interactions over all gene pairs (at FDR 0.01) for each feature is shown. Blue: negative interactions, yellow: positive interactions. The lower panel shows the …
Figure 3 with 2 supplements
A landscape of statistical genetic interactions.
(A) Correlation network of genetic interaction profiles. Pearson correlation coefficients were computed for each pair of genes using the profile of all genetic interactions of these two genes to all …
Figure 3—figure supplement 1
Heatmap of multi-parametric genetic interactions.
Heatmap of all interaction coefficients between 1293 target genes and 72 query genes for nine of the phenotypic features. Blue colour indicates negative genetic interactions and yellow are positive …
Figure 3—figure supplement 2
Genetic interaction profiles and protein complexes.
Distribution of pairwise Pearson correlation coefficients across 21 phenotypes for gene pairs detected by co-purification and mass spectrometry according to the DPiM dataset (Guruharsha et al., 2011)…
Figure 4 with 2 supplements
Deriving directional genetic interactions.
(A) Multiparametric phenotypes are extracted for single and double knockdowns. Genetic interaction scores are computed for each double knockdown experiment. The schematic plots in the third column …
Figure 4—figure supplement 1
Directed genetic interactions.
Example when a direction of the genetic interaction is not determined. The pairwise interaction (π) is not parallel to one of the single gene effects.
Figure 4—figure supplement 2
Inference of directed genetic interaction of Cdc23 and sti.
Testing for directed genetic interactions for the gene pair Cdc23 and sti. Fit of the 21-dimensional π-score vector as linear function of the single gene effects. Each dot shows the π-score and …
Figure 5
An epistatic network of mitotic genes.
(A) Graph showing data-derived epistatic interactions of genes that are key regulators of cell cycle events, including polo, and members of the γTuRC, SAC, APC/C, the dynein/dynactin complex, sister …
Figure 6 with 1 supplement
Genetic interactions between Ras signalling and chromatin remodelling.
(A) Edges show the detected genetic interactions in the interaction screen of members of the SWI/SNF complex with RasGAP1 and members of the Ras pathway. An edge is drawn if a significant …
Figure 6—figure supplement 1
Ras-induced cell growth requires SWI/SNF complex function.
Cell viability of parental HCT116 KRAS mutant cells (KRASG13D/+) and isogenic HCT116 KRAS wild type cells (KRASKO/+).
Figure 7
Recurrently mutated genes.
(A–E) Subnetworks showing detected directional genetic interactions of recurrently mutated cancer genes. Recurrently mutated genes as reported by Tamborero et al. (2013) are coloured dark. Red …
Tables
Table 1
siRNAs
| Gene | Target sequence | Cat # |
|---|---|---|
| CTRL/control | SIGENOME NON TARGET POOLNO2 | D-00120614-20 |
| ARID1A | GCAACGACAUGAUUCCUAU | MU-017263-01 (siGENOME) D-017263-01 |
| ARID1A | GAAUAGGGCCUGAGGGAAA | MU-017263-01 (siGENOME) D-017263-02 |
| ARID1A | AGAUGUGGGUGGACCGUUA | MU-017263-01 (siGENOME) D-017263-03 |
| ARID1A | UAGUAUGGCUGGCAUGAUC | MU-017263-01 (siGENOME) D-017263-04 |
| SMARCA4 | GAAAGGAGCUGCCCGAGUA | MU-010431-00 (siGENOME) D-010431-01 |
| SMARCA4 | CCAAGGAUUUCAAGGAAUA | MU-010431-00 (siGENOME) D-010431-02 |
| SMARCA4 | GAAAGUGGCUCAGAAGAAG | MU-010431-00 (siGENOME) D-010431-03 |
| SMARCA4 | AGACAGCCCUCAAUGCUAA | MU-010431-00 (siGENOME) D-010431-04 |
| SMARCB1 | GAAACUACCUCCGUAUGUU | MU-010536-01 (siGENOME) D-010536-01 |
| SMARCB1 | CCACAACCAUCAACAGGAA | MU-010536-01 (siGENOME) D-010536-02 |
| SMARCB1 | GUGACGAUCUGGAUUUGAA | MU-010536-01 (siGENOME) D-010536-03 |
| SMARCB1 | AGACCUACGCCUUCAGCGA | MU-010536-01 (siGENOME) D-010536-04 |
Additional files
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Supplementary file 1
A table of primer and dsRNA sequences for all targeted genes.
- https://doi.org/10.7554/eLife.05464.019
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Supplementary file 2
A table of query genes.
- https://doi.org/10.7554/eLife.05464.020
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Supplementary file 3
A table of extracted features.
- https://doi.org/10.7554/eLife.05464.021
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Supplementary file 4
A table of selected non-redundant features.
- https://doi.org/10.7554/eLife.05464.022
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Supplementary file 5
A table of genes passed quality control.
- https://doi.org/10.7554/eLife.05464.023
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Supplementary file 6
A table of directed genetic interactions.
- https://doi.org/10.7554/eLife.05464.024
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Source code 1
Documented source code for reproducing all figures and tables.
- https://doi.org/10.7554/eLife.05464.025
