ArticleMolecular systems biology2012
Single-cell analysis of population context advances RNAi screening at multiple levels.
Article in Molecular systems biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers.
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Who cites it
93 citing papers in PubMed.
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- Making Rift Valley Fever Viral Particles Fluorescent.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Learning single-cell perturbation responses using neural optimal transport.Nature methods · 2023Article
- Extended methods for spatial cell classification with DBSCAN-CellX.Scientific reports · 2023Article
- Cellular state landscape and herpes simplex virus type 1 infection progression are connected.Nature communications · 2023Article
- Modelling viral encephalitis caused by herpes simplex virus 1 infection in cerebral organoids.Nature microbiology · 2023Article
- Single therapeutic dose of an antiviral UL29 siRNA swarm diminishes symptoms and viral load of mice infected intranasally with HSV-1.Smart medicine · 2023Article
- Adenovirus entry: Stability, uncoating, and nuclear import.Molecular microbiology · 2022Review
- Swarms of chemically modified antiviral siRNA targeting herpes simplex virus infection in human corneal epithelial cells.PLoS pathogens · 2022Article
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- Two years into COVID-19 - Lessons in SARS-CoV-2 and a perspective from papers in FEBS Letters.FEBS letters · 2021Review
- Infection-induced chromatin modifications facilitate translocation of herpes simplex virus capsids to the inner nuclear membrane.PLoS pathogens · 2021Article
- Organoids in image-based phenotypic chemical screens.Experimental & molecular medicine · 2021Review
- Human IFITM3 restricts chikungunya virus and Mayaro virus infection and is susceptible to virus-mediated counteraction.Life science alliance · 2021Article
- High content genome-wide siRNA screen to investigate the coordination of cell size and RNA production.Scientific data · 2021Article
33 more citing papers are in PubMed but not listed here.
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28 authors.
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Abstract
Isogenic cells in culture show strong variability, which arises from dynamic adaptations to the microenvironment of individual cells. Here we study the influence of the cell population context, which determines a single cell's microenvironment, in image-based RNAi screens. We developed a comprehensive computational approach that employs Bayesian and multivariate methods at the single-cell level. We applied these methods to 45 RNA interference screens of various sizes, including 7 druggable genome and 2 genome-wide screens, analysing 17 different mammalian virus infections and four related cell physiological processes. Analysing cell-based screens at this depth reveals widespread RNAi-induced changes in the population context of individual cells leading to indirect RNAi effects, as well as perturbations of cell-to-cell variability regulators. We find that accounting for indirect effects improves the consistency between siRNAs targeted against the same gene, and between replicate RNAi screens performed in different cell lines, in different labs, and with different siRNA libraries. In an era where large-scale RNAi screens are increasingly performed to reach a systems-level understanding of cellular processes, we show that this is often improved by analyses that account for and incorporate the single-cell microenvironment.
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