ArticlePloS one2015
Morphological Profiles of RNAi-Induced Gene Knockdown Are Highly Reproducible but Dominated by Seed Effects.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Imaging phenotype reveals that disulfirams induce protein insolubility in the mitochondrial matrix.Scientific reports · 2024Article
- A Decade in a Systematic Review: The Evolution and Impact of Cell Painting.bioRxiv : the preprint server for biology · 2024Article
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- Image-based profiling for drug discovery: due for a machine-learning upgrade?Nature reviews. Drug discovery · 2021Review
- Virtual organelle self-coding for fluorescence imaging via adversarial learning.Journal of biomedical optics · 2020Article
- Deep learning predicts function of live retinal pigment epithelium from quantitative microscopy.The Journal of clinical investigation · 2020Article
- Heterogeneous response of endothelial cells to insulin-like growth factor 1 treatment is explained by spatially clustered sub-populations.Biology open · 2019Article
- Systematic exploration of cell morphological phenotypes associated with a transcriptomic query.Nucleic acids research · 2018Article
- Growth-restricting effects of siRNA transfections: a largely deterministic combination of off-target binding and hybridization-independent competition.Nucleic acids research · 2018Article
- Evaluation and control of miRNA-like off-target repression for RNA interference.Cellular and molecular life sciences : CMLS · 2018Review
- RNA Interference (RNAi) Screening inGenetics · 2018Article
- Am I ready for CRISPR? A user's guide to genetic screens.Nature reviews. Genetics · 2018Review
- Large-scale image-based profiling of single-cell phenotypes in arrayed CRISPR-Cas9 gene perturbation screens.Molecular systems biology · 2018Article
- Evaluation of RNAi and CRISPR technologies by large-scale gene expression profiling in the Connectivity Map.PLoS biology · 2017Article
- High-Throughput Imaging for the Discovery of Cellular Mechanisms of Disease.Trends in genetics : TIG · 2017Review
- Genome-scale CRISPR pooled screens.Analytical biochemistry · 2017Article
- Data-analysis strategies for image-based cell profiling.Nature methods · 2017Article
- RIsearch2: suffix array-based large-scale prediction of RNA-RNA interactions and siRNA off-targets.Nucleic acids research · 2017Article
- Article
- Profiling DNA damage response following mitotic perturbations.Nature communications · 2016Article
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Authors and funding
9 authors.
Funding
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Abstract
RNA interference and morphological profiling-the measurement of thousands of phenotypes from individual cells by microscopy and image analysis-are a potentially powerful combination. We show that morphological profiles of RNAi-induced knockdown using the Cell Painting assay are in fact highly sensitive and reproducible. However, we find that the magnitude and prevalence of off-target effects via the RNAi seed-based mechanism make morphological profiles of RNAi reagents targeting the same gene look no more similar than reagents targeting different genes. Pairs of RNAi reagents that share the same seed sequence produce image-based profiles that are much more similar to each other than profiles from pairs designed to target the same gene, a phenomenon previously observed in small-scale gene-expression profiling experiments. Various strategies have been used to enrich on-target versus off-target effects in the context of RNAi screening where a narrow set of phenotypes are measured, mostly based on comparing multiple sequences targeting the same gene; however, new approaches will be needed to make RNAi morphological profiling (that is, comparing multi-dimensional phenotypes) viable. We have shared our raw data and computational pipelines to facilitate research.
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