The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
Single‐cell analysis of population context advances RNAi screening at multiple levels
Open accessAbstract
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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Cites
DAVID: Database for Annotation, Visualization, and Integrated Discovery
Dennis, G., Sherman, B. T., Hosack, D. A., Yang, J., Gao, W., Lane, H. C., & Lempicki, R. A. (2003) · Genome Biology · doi:10.1186/gb-2003-4-5-p3 · Cited by 9,327
Stochastic Gene Expression in a Single Cell
Elowitz, M. B., Levine, A. J., Siggia, E. D., & Swain, P. S. (2002) · Science · doi:10.1126/science.1070919 · Cited by 5,441
Hopkins, A. L., & Groom, C. R. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd892 · Cited by 3,305
Doherty, G. J., & McMahon, H. T. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.78.081307.110540 · Cited by 3,075
Expression profiling reveals off-target gene regulation by RNAi
Jackson, A. L., Bartz, S. R., Schelter, J., Kobayashi, S. V., Burchard, J., Mao, M., Li, B., Cavet, G., & Linsley, P. S. (2003) · Nature Biotechnology · doi:10.1038/nbt831 · Cited by 2,370
Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise
Newman, J. R. S., Ghaemmaghami, S., Ihmels, J., Breslow, D. K., Noble, M., DeRisi, J. L., & Weissman, J. S. (2006) · Nature · doi:10.1038/nature04785 · Cited by 1,483
High-throughput RNAi screening in cultured cells: a user's guide
Echeverri, C. J., & Perrimon, N. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1836 · Cited by 380 · cited 1×
“It is however currently unclear if and how population context effects contribute to the challenges present in RNA interference (RNAi) screens (Echeverri and Perrimon, 2006; Moffat and Sabatini, 2006; Cherry, 2009; Mohr et al, 2010).”
Cited by
Data-analysis strategies for image-based cell profiling
Caicedo, J. C., Cooper, S., Heigwer, F., Warchal, S., Qiu, P., Molnar, C., Vasilevich, A. S., Barry, J. D., Bansal, H. S., Kraus, O., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4397 · Cited by 739
Multiplexed protein maps link subcellular organization to cellular states
Gut, G., Herrmann, M. D., & Pelkmans, L. (2018) · Science · doi:10.1126/science.aar7042 · Cited by 510
Self-citationA Critical and Comparative Review of Fluorescent Tools for Live-Cell Imaging
Specht, E. A., Braselmann, E., & Palmer, A. E. (2017) · Annual Review of Physiology · doi:10.1146/annurev-physiol-022516-034055 · Cited by 444
Microscopy-Based High-Content Screening
Boutros, M., Heigwer, F., & Laufer, C. (2015) · Cell · doi:10.1016/j.cell.2015.11.007 · Cited by 396
Coronavirus Cell Entry Occurs through the Endo-/Lysosomal Pathway in a Proteolysis-Dependent Manner
Burkard, C., Verheije, M. H., Wicht, O., van Kasteren, S. I., van Kuppeveld, F. J., Haagmans, B. L., Pelkmans, L., Rottier, P. J. M., Bosch, B. J., & de Haan, C. A. M. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004502 · Cited by 388
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Metadata
- Authors
- Snijder, B., Sacher, R., Rämö, P., Liberali, P., Mench, K., Wolfrum, N., Burleigh, L., Scott, C. C., Verheije, M. H., Mercer, J., Moese, S., Heger, T., Theusner, K., Jurgeit, A., Lamparter, D., Balistreri, G., Schelhaas, M., De Haan, C. A. M., Marjomäki, V., Hyypiä, T., Rottier, P. J. M., Sodeik, B., Marsh, M., Gruenberg, J., Amara, A., Greber, U., Helenius, A., & Pelkmans, L.
- Venue
- Molecular Systems Biology
- Published
- 2012-01
- Volume
- 8
- Issue
- 1
- Pages
- 579-579
- ISSN
- 1744-4292 (ISSN-L)
- OpenAlex
- W2158900785
- Cited by
- 169
- References
- 7
- FWCI
- 9.56
- Type
- journal article
- Language
- en
- Open access
- gold
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