DOI: 10.1083/jcb.200910105. Automated microscopy for high-content RNAi screening

Automated microscopy for high-content RNAi screening

10.1083/jcb.200910105

Crossref journal-article

Rockefeller University Press

Journal of Cell Biology (291)

Abstract

Fluorescence microscopy is one of the most powerful tools to investigate complex cellular processes such as cell division, cell motility, or intracellular trafficking. The availability of RNA interference (RNAi) technology and automated microscopy has opened the possibility to perform cellular imaging in functional genomics and other large-scale applications. Although imaging often dramatically increases the content of a screening assay, it poses new challenges to achieve accurate quantitative annotation and therefore needs to be carefully adjusted to the specific needs of individual screening applications. In this review, we discuss principles of assay design, large-scale RNAi, microscope automation, and computational data analysis. We highlight strategies for imaging-based RNAi screening adapted to different library and assay designs.

Bibliography

Conrad, C., & Gerlich, D. W. (2010). Automated microscopy for high-content RNAi screening. Journal of Cell Biology, 188(4), 453â461.

Authors 2

Christian Conrad (first)
Daniel W. Gerlich (additional)

References 86 Referenced 121

10.1016/j.cbpa.2009.07.009 / Curr. Opin. Chem. Biol. / Fluorescent biosensors for real-time tracking of post-translational modification dynamics by Aye-Han (2009)
10.1126/science.1140324 / Science. / Quantitative morphological signatures define local signaling networks regulating cell morphology by Bakal (2007)
10.1016/j.cmet.2009.05.009 / Cell Metab. / Identification of cholesterol-regulating genes by targeted RNAi screening by Bartz (2009)
10.1038/nmeth854 / Nat. Methods. / 3′ UTR seed matches, but not overall identity, are associated with RNAi off-targets by Birmingham (2006)
10.1038/nmeth.1351 / Nat. Methods. / Statistical methods for analysis of high-throughput RNA interference screens by Birmingham (2009)
10.1093/bioinformatics/17.12.1213 / Bioinformatics. / A neural network classifier capable of recognizing the patterns of all major subcellular structures in fluorescence microscope images of HeLa cells by Boland (2001)
10.1126/science.1091266 / Science. / Genome-wide RNAi analysis of growth and viability in Drosophila cells by Boutros (2004)
10.1186/gb-2006-7-7-r66 / Genome Biol. / Analysis of cell-based RNAi screens by Boutros (2006)
10.1126/science.1152725 / Science. / Identification of host proteins required for HIV infection through a functional genomic screen by Brass (2008)
10.1038/ng1201-365 / Nat. Genet. / Minimum information about a microarray experiment (MIAME)-toward standards for microarray data by Brazma (2001)
10.1038/nmeth912 / Nat. Methods. / Enzymatically prepared RNAi libraries by Buchholz (2006)
10.1016/j.copbio.2008.06.003 / Curr. Opin. Biotechnol. / Fluorescence-based methods in the study of protein-protein interactions in living cells by Ciruela (2008)
10.1101/gr.2383804 / Genome Res. / Automatic identification of subcellular phenotypes on human cell arrays by Conrad (2004)
10.1186/gb-2007-8-9-r203 / Genome Biol. / A case study of the reproducibility of transcriptional reporter cell-based RNAi screens in Drosophila by DasGupta (2007)
10.1016/j.cell.2008.12.041 / Cell. / RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins by Doil (2009)
10.1038/ncb1569 / Nat. Cell Biol. / A functional genomic screen identifies a role for TAO1 kinase in spindle-checkpoint signalling by Draviam (2007)
10.1016/j.cub.2004.08.063 / Curr. Biol. / Terminal cytokinesis events uncovered after an RNAi screen by Echard (2004)
10.1038/nmeth1006-777 / Nat. Methods. / Minimizing the risk of reporting false positives in large-scale RNAi screens by Echeverri (2006)
10.1038/35078107 / Nature. / Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells by Elbashir (2001)
{'key': '2023072905032556200_bib20', 'first-page': '155', 'article-title': 'Production of siRNA- and cDNA-transfected cell arrays on noncoated chambered coverglass for high-content screening microscopy in living cells', 'volume': '360', 'author': 'Erfle', 'year': '2007', 'journal-title': 'Methods Mol. Biol.'} / Methods Mol. Biol. / Production of siRNA- and cDNA-transfected cell arrays on noncoated chambered coverglass for high-content screening microscopy in living cells by Erfle (2007)
10.2144/04373RT01 / Biotechniques. / siRNA cell arrays for high-content screening microscopy by Erfle (2004)
10.1038/nprot.2006.483 / Nat. Protoc. / Reverse transfection on cell arrays for high content screening microscopy by Erfle (2007)
10.1177/1087057108320133 / J. Biomol. Screen. / Work flow for multiplexing siRNA assays by solid-phase reverse transfection in multiwell plates by Erfle (2008)
10.1038/35888 / Nature. / Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans by Fire (1998)
10.1093/nar/gkj114 / Nucleic Acids Res. / FlyRNAi: the Drosophila RNAi screening center database by Flockhart (2006)
{'key': '2023072905032556200_bib26', 'first-page': 'S14', 'article-title': '4D imaging to assay complex dynamics in live specimens', 'volume': 'Suppl', 'author': 'Gerlich', 'year': '2003', 'journal-title': 'Nat. Cell Biol.'} / Nat. Cell Biol. / 4D imaging to assay complex dynamics in live specimens by Gerlich (2003)
10.1038/ncb0901-852 / Nat. Cell Biol. / Four-dimensional imaging and quantitative reconstruction to analyse complex spatiotemporal processes in live cells by Gerlich (2001)
10.1126/science.1124618 / Science. / The fluorescent toolbox for assessing protein location and function by Giepmans (2006)
10.1016/j.devcel.2006.12.007 / Dev. Cell. / Automated subcellular location determination and high-throughput microscopy by Glory (2007)
10.1186/gb-2005-6-5-r47 / Genome Biol. / The Open Microscopy Environment (OME) Data Model and XML file: open tools for informatics and quantitative analysis in biological imaging by Goldberg (2005)
10.1038/35042526 / Nature. / Functional genomic analysis of cell division in C. elegans using RNAi of genes on chromosome III by Gönczy (2000)
10.1038/nmeth1008 / Nat. Methods. / Single-cell quantification of molecules and rates using open-source microscope-based cytometry by Gordon (2007)
10.1126/science.1141314 / Science. / Genes required for mitotic spindle assembly in Drosophila S2 cells by Goshima (2007)
10.1093/nar/gkh110 / Nucleic Acids Res. / RNAiDB and PhenoBlast: web tools for genome-wide phenotypic mapping projects by Gunsalus (2004)
10.1109/TSMC.1973.4309314 / IEEE Trans. Syst. Man Cybern. / Textural features for image classification by Haralick (1973)
10.1101/gr.092494.109 / Genome Res. / Automatic analysis of dividing cells in live cell movies to detect mitotic delays and correlate phenotypes in time by Harder (2009)
10.1038/35011540 / Nature. / From molecular to modular cell biology by Hartwell (1999)
10.1146/annurev.biophys.36.040306.132612 / Annu. Rev. Biophys. Biomol. Struct. / Fluorescence correlation spectroscopy: novel variations of an established technique by Haustein (2007)
10.1261/rna.25706 / RNA. / Widespread siRNA “off-target” transcript silencing mediated by seed region sequence complementarity by Jackson (2006)
10.1093/nar/gkn760 / Nucleic Acids Res. / STRING 8—a global view on proteins and their functional interactions in 630 organisms by Jensen (2009)
10.1126/science.1175145 / Science. / Genome-wide RNAi screen identifies Letm1 as a mitochondrial Ca2+/H+ antiporter by Jiang (2009)
10.1038/nchembio0209-63 / Nat. Chem. Biol. / Visualizing biochemical activities in living cells by Johnsson (2009)
10.1186/1471-2105-9-482 / BMC Bioinformatics. / CellProfiler Analyst: data exploration and analysis software for complex image-based screens by Jones (2008)
10.1073/pnas.0808843106 / Proc. Natl. Acad. Sci. USA. / Scoring diverse cellular morphologies in image-based screens with iterative feedback and machine learning by Jones (2009)
10.1016/S0960-9822(98)70156-3 / Curr. Biol. / Histone-GFP fusion protein enables sensitive analysis of chromosome dynamics in living mammalian cells by Kanda (1998)
10.1126/science.1165620 / Science. / The automation of science by King (2009)
10.1038/ncb1659 / Nat. Cell Biol. / Genome-scale RNAi profiling of cell division in human tissue culture cells by Kittler (2007)
10.1038/nmeth1089 / Nat. Methods. / A probability-based approach for the analysis of large-scale RNAi screens by König (2007)
10.1038/nature07207 / Nature. / RNA interference screen for human genes associated with West Nile virus infection by Krishnan (2008)
{'key': '2023072905032556200_bib50', 'first-page': 'S7', 'article-title': 'Photobleaching and photoactivation: following protein dynamics in living cells', 'volume': 'Suppl', 'author': 'Lippincott-Schwartz', 'year': '2003', 'journal-title': 'Nat. Cell Biol.'} / Nat. Cell Biol. / Photobleaching and photoactivation: following protein dynamics in living cells by Lippincott-Schwartz (2003)
10.1186/gb-2009-10-3-r26 / Genome Biol. / Parallel RNAi screens across different cell lines identify generic and cell type-specific regulators of actin organization and cell morphology by Liu (2009)
10.1038/nmeth1032 / Nat. Methods. / Image-based multivariate profiling of drug responses from single cells by Loo (2007)
10.1016/j.cell.2007.08.031 / Cell. / Imaging in systems biology by Megason (2007)
10.1038/nature02873 / Nature. / Mechanisms of gene silencing by double-stranded RNA by Meister (2004)
10.1016/S0091-679X(08)85024-8 / Methods Cell Biol. / Open tools for storage and management of quantitative image data by Moore (2008)
10.1073/pnas.0604320103 / Proc. Natl. Acad. Sci. USA. / Genome-wide functional analysis of human cell-cycle regulators by Mukherji (2006)
10.1038/nature03869 / Nature. / Identification of JAK/STAT signalling components by genome-wide RNA interference by Müller (2005)
10.1038/nmeth876 / Nat. Methods. / High-throughput RNAi screening by time-lapse imaging of live human cells by Neumann (2006)
10.1038/nature08869 / Nature. / Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes by Neumann (2010)
10.1038/nature03571 / Nature. / Genome-wide analysis of human kinases in clathrin- and caveolae/raft-mediated endocytosis by Pelkmans (2005)
10.1038/nrm1979 / Nat. Rev. Mol. Cell Biol. / High-throughput fluorescence microscopy for systems biology by Pepperkok (2006)
10.1126/science.1100709 / Science. / Multidimensional drug profiling by automated microscopy by Perlman (2004)
10.1073/pnas.0802982105 / Proc. Natl. Acad. Sci. USA. / In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen by Plouffe (2008)
10.1038/nmeth.1199 / Nat. Methods. / BAC TransgeneOmics: a high-throughput method for exploration of protein function in mammals by Poser (2008)
10.1016/1049-9652(92)90027-U / CVGIP: Graphical Models and Image Processing. / A survey of moment-based techniques for unoccluded object representation and recognition by Prokop (1992)
10.1093/bioinformatics/btp524 / Bioinformatics. / CellClassifier: supervised learning of cellular phenotypes by Rämö (2009)
10.1038/nmeth924 / Nat. Methods. / Genome-scale loss-of-function screening with a lentiviral RNAi library by Root (2006)
10.1007/978-1-60327-993-2_7 / Methods Mol. Biol. / Automated live microscopy to study mitotic gene function in fluorescent reporter cell lines by Schmitz (2009)
10.1016/S0076-6879(06)14032-X / Methods Enzymol. / Digital autofocus methods for automated microscopy by Shen (2006)
10.1038/nmeth892 / Nat. Methods. / Dynamic proteomics in individual human cells uncovers widespread cell-cycle dependence of nuclear proteins by Sigal (2006)
10.1126/science.1097931 / Science. / Dissection of the mammalian midbody proteome reveals conserved cytokinesis mechanisms by Skop (2004)
10.1038/nature08282 / Nature. / Population context determines cell-to-cell variability in endocytosis and virus infection by Snijder (2009)
10.1038/nmeth927 / Nat. Methods. / Expressing short hairpin RNAs in vivo by Snøve (2006)
10.1038/nature03353 / Nature. / Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans by Sönnichsen (2005)
10.1016/j.cell.2008.12.020 / Cell. / Aurora B-mediated abscission checkpoint protects against tetraploidization by Steigemann (2009)
10.1126/science.1082602 / Science. / Informatics and quantitative analysis in biological imaging by Swedlow (2003)
10.1016/j.cbpa.2008.01.020 / Curr. Opin. Chem. Biol. / Fluorescent biosensors of protein function by VanEngelenburg (2008)
10.1109/ICPR.1996.546931 / Proceedings of the 13th International Conference on Pattern Recognition. / Statistical geometric features-extensions for cytological texture analysis by Walker (1996)
10.1016/j.jsb.2009.10.004 / J. Struct. Biol. / Automatic identification and clustering of chromosome phenotypes in a genome wide RNAi screen by time-lapse imaging by Walter (2009)
10.1038/nmeth914 / Nat. Methods. / Tuning silence: conditional systems for RNA interference by Wiznerowicz (2006)
10.1073/pnas.152327299 / Proc. Natl. Acad. Sci. USA. / Short RNA duplexes produced by hydrolysis with Escherichia coli RNase III mediate effective RNA interference in mammalian cells by Yang (2002)
10.1186/1471-2105-9-264 / BMC Bioinformatics. / Using iterative cluster merging with improved gap statistics to perform online phenotype discovery in the context of high-throughput RNAi screens by Yin (2008)
10.1177/108705719900400206 / J. Biomol. Screen. / A simple statistical parameter for use in evaluation and validation of high throughput screening assays by Zhang (1999)
10.1093/nar/gkn435 / Nucleic Acids Res. / Hit selection with false discovery rate control in genome-scale RNAi screens by Zhang (2008)
10.1109/TITB.2008.2007098 / IEEE Trans. Inf. Technol. Biomed. / A novel cell segmentation method and cell phase identification using Markov model by Zhou (2009)
10.1038/35075114 / Nature. / Microarrays of cells expressing defined cDNAs by Ziauddin (2001)

Dates

Type	When
Created	15 years, 6 months ago (Feb. 22, 2010, 3:03 p.m.)
Deposited	2 years ago (July 29, 2023, 1:06 a.m.)
Indexed	9 months ago (Nov. 19, 2024, 11:20 a.m.)
Issued	15 years, 6 months ago (Feb. 22, 2010)
Published	15 years, 6 months ago (Feb. 22, 2010)
Published Online	15 years, 6 months ago (Feb. 22, 2010)
Published Print	15 years, 6 months ago (Feb. 22, 2010)

Funders 0

None

BibTeX

@article{Conrad_2010, title={Automated microscopy for high-content RNAi screening}, volume={188}, ISSN={0021-9525}, url={http://dx.doi.org/10.1083/jcb.200910105}, DOI={10.1083/jcb.200910105}, number={4}, journal={Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Conrad, Christian and Gerlich, Daniel W.}, year={2010}, month=feb, pages={453–461} }

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      "DOI": "10.1038/nmeth854",
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      "volume": "3",
      "author": "Birmingham",
      "year": "2006",
      "journal-title": "Nat. Methods."
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      "doi-asserted-by": "publisher",
      "first-page": "569",
      "DOI": "10.1038/nmeth.1351",
      "article-title": "Statistical methods for analysis of high-throughput RNA interference screens",
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      "author": "Birmingham",
      "year": "2009",
      "journal-title": "Nat. Methods."
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    {
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      "first-page": "1213",
      "DOI": "10.1093/bioinformatics/17.12.1213",
      "article-title": "A neural network classifier capable of recognizing the patterns of all major subcellular structures in fluorescence microscope images of HeLa cells",
      "volume": "17",
      "author": "Boland",
      "year": "2001",
      "journal-title": "Bioinformatics."
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      "doi-asserted-by": "publisher",
      "first-page": "832",
      "DOI": "10.1126/science.1091266",
      "article-title": "Genome-wide RNAi analysis of growth and viability in Drosophila cells",
      "volume": "303",
      "author": "Boutros",
      "year": "2004",
      "journal-title": "Science."
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    {
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      "doi-asserted-by": "publisher",
      "first-page": "R66",
      "DOI": "10.1186/gb-2006-7-7-r66",
      "article-title": "Analysis of cell-based RNAi screens",
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      "author": "Boutros",
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      "article-title": "Minimum information about a microarray experiment (MIAME)-toward standards for microarray data",
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      "author": "Brazma",
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      "author": "Draviam",
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      "first-page": "1685",
      "DOI": "10.1016/j.cub.2004.08.063",
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      "first-page": "777",
      "DOI": "10.1038/nmeth1006-777",
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      "author": "Echeverri",
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      "first-page": "494",
      "DOI": "10.1038/35078107",
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      "author": "Elbashir",
      "year": "2001",
      "journal-title": "Nature."
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      "author": "Erfle",
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      "DOI": "10.2144/04373RT01",
      "article-title": "siRNA cell arrays for high-content screening microscopy",
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      "author": "Erfle",
      "year": "2004",
      "journal-title": "Biotechniques."
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      "first-page": "575",
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      "volume": "13",
      "author": "Erfle",
      "year": "2008",
      "journal-title": "J. Biomol. Screen."
    },
    {
      "key": "2023072905032556200_bib24",
      "doi-asserted-by": "publisher",
      "first-page": "806",
      "DOI": "10.1038/35888",
      "article-title": "Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans",
      "volume": "391",
      "author": "Fire",
      "year": "1998",
      "journal-title": "Nature."
    },
    {
      "key": "2023072905032556200_bib25",
      "doi-asserted-by": "publisher",
      "first-page": "D489",
      "DOI": "10.1093/nar/gkj114",
      "article-title": "FlyRNAi: the Drosophila RNAi screening center database",
      "volume": "34",
      "author": "Flockhart",
      "year": "2006",
      "journal-title": "Nucleic Acids Res."
    },
    {
      "key": "2023072905032556200_bib26",
      "first-page": "S14",
      "article-title": "4D imaging to assay complex dynamics in live specimens",
      "volume": "Suppl",
      "author": "Gerlich",
      "year": "2003",
      "journal-title": "Nat. Cell Biol."
    },
    {
      "key": "2023072905032556200_bib27",
      "doi-asserted-by": "publisher",
      "first-page": "852",
      "DOI": "10.1038/ncb0901-852",
      "article-title": "Four-dimensional imaging and quantitative reconstruction to analyse complex spatiotemporal processes in live cells",
      "volume": "3",
      "author": "Gerlich",
      "year": "2001",
      "journal-title": "Nat. Cell Biol."
    },
    {
      "key": "2023072905032556200_bib28",
      "doi-asserted-by": "publisher",
      "first-page": "217",
      "DOI": "10.1126/science.1124618",
      "article-title": "The fluorescent toolbox for assessing protein location and function",
      "volume": "312",
      "author": "Giepmans",
      "year": "2006",
      "journal-title": "Science."
    },
    {
      "key": "2023072905032556200_bib29",
      "doi-asserted-by": "publisher",
      "first-page": "7",
      "DOI": "10.1016/j.devcel.2006.12.007",
      "article-title": "Automated subcellular location determination and high-throughput microscopy",
      "volume": "12",
      "author": "Glory",
      "year": "2007",
      "journal-title": "Dev. Cell."
    },
    {
      "key": "2023072905032556200_bib30",
      "doi-asserted-by": "publisher",
      "first-page": "R47",
      "DOI": "10.1186/gb-2005-6-5-r47",
      "article-title": "The Open Microscopy Environment (OME) Data Model and XML file: open tools for informatics and quantitative analysis in biological imaging",
      "volume": "6",
      "author": "Goldberg",
      "year": "2005",
      "journal-title": "Genome Biol."
    },
    {
      "key": "2023072905032556200_bib31",
      "doi-asserted-by": "publisher",
      "first-page": "331",
      "DOI": "10.1038/35042526",
      "article-title": "Functional genomic analysis of cell division in C. elegans using RNAi of genes on chromosome III",
      "volume": "408",
      "author": "G\u00f6nczy",
      "year": "2000",
      "journal-title": "Nature."
    },
    {
      "key": "2023072905032556200_bib32",
      "doi-asserted-by": "publisher",
      "first-page": "175",
      "DOI": "10.1038/nmeth1008",
      "article-title": "Single-cell quantification of molecules and rates using open-source microscope-based cytometry",
      "volume": "4",
      "author": "Gordon",
      "year": "2007",
      "journal-title": "Nat. Methods."
    },
    {
      "key": "2023072905032556200_bib33",
      "doi-asserted-by": "publisher",
      "first-page": "417",
      "DOI": "10.1126/science.1141314",
      "article-title": "Genes required for mitotic spindle assembly in Drosophila S2 cells",
      "volume": "316",
      "author": "Goshima",
      "year": "2007",
      "journal-title": "Science."
    },
    {
      "key": "2023072905032556200_bib34",
      "doi-asserted-by": "publisher",
      "first-page": "D406",
      "DOI": "10.1093/nar/gkh110",
      "article-title": "RNAiDB and PhenoBlast: web tools for genome-wide phenotypic mapping projects",
      "volume": "32",
      "author": "Gunsalus",
      "year": "2004",
      "journal-title": "Nucleic Acids Res."
    },
    {
      "key": "2023072905032556200_bib35",
      "doi-asserted-by": "publisher",
      "first-page": "610",
      "DOI": "10.1109/TSMC.1973.4309314",
      "article-title": "Textural features for image classification",
      "volume": "3",
      "author": "Haralick",
      "year": "1973",
      "journal-title": "IEEE Trans. Syst. Man Cybern."
    },
    {
      "key": "2023072905032556200_bib36",
      "doi-asserted-by": "publisher",
      "first-page": "2113",
      "DOI": "10.1101/gr.092494.109",
      "article-title": "Automatic analysis of dividing cells in live cell movies to detect mitotic delays and correlate phenotypes in time",
      "volume": "19",
      "author": "Harder",
      "year": "2009",
      "journal-title": "Genome Res."
    },
    {
      "key": "2023072905032556200_bib37",
      "doi-asserted-by": "publisher",
      "first-page": "C47",
      "DOI": "10.1038/35011540",
      "article-title": "From molecular to modular cell biology",
      "volume": "402",
      "author": "Hartwell",
      "year": "1999",
      "journal-title": "Nature."
    },
    {
      "key": "2023072905032556200_bib38",
      "doi-asserted-by": "publisher",
      "first-page": "151",
      "DOI": "10.1146/annurev.biophys.36.040306.132612",
      "article-title": "Fluorescence correlation spectroscopy: novel variations of an established technique",
      "volume": "36",
      "author": "Haustein",
      "year": "2007",
      "journal-title": "Annu. Rev. Biophys. Biomol. Struct."
    },
    {
      "key": "2023072905032556200_bib39",
      "doi-asserted-by": "publisher",
      "first-page": "1179",
      "DOI": "10.1261/rna.25706",
      "article-title": "Widespread siRNA \u201coff-target\u201d transcript silencing mediated by seed region sequence complementarity",
      "volume": "12",
      "author": "Jackson",
      "year": "2006",
      "journal-title": "RNA."
    },
    {
      "key": "2023072905032556200_bib40",
      "doi-asserted-by": "publisher",
      "first-page": "D412",
      "DOI": "10.1093/nar/gkn760",
      "article-title": "STRING 8\u2014a global view on proteins and their functional interactions in 630 organisms",
      "volume": "37",
      "author": "Jensen",
      "year": "2009",
      "journal-title": "Nucleic Acids Res."
    },
    {
      "key": "2023072905032556200_bib41",
      "doi-asserted-by": "publisher",
      "first-page": "144",
      "DOI": "10.1126/science.1175145",
      "article-title": "Genome-wide RNAi screen identifies Letm1 as a mitochondrial Ca2+/H+ antiporter",
      "volume": "326",
      "author": "Jiang",
      "year": "2009",
      "journal-title": "Science."
    },
    {
      "key": "2023072905032556200_bib42",
      "doi-asserted-by": "publisher",
      "first-page": "63",
      "DOI": "10.1038/nchembio0209-63",
      "article-title": "Visualizing biochemical activities in living cells",
      "volume": "5",
      "author": "Johnsson",
      "year": "2009",
      "journal-title": "Nat. Chem. Biol."
    },
    {
      "key": "2023072905032556200_bib43",
      "doi-asserted-by": "publisher",
      "first-page": "482",
      "DOI": "10.1186/1471-2105-9-482",
      "article-title": "CellProfiler Analyst: data exploration and analysis software for complex image-based screens",
      "volume": "9",
      "author": "Jones",
      "year": "2008",
      "journal-title": "BMC Bioinformatics."
    },
    {
      "key": "2023072905032556200_bib44",
      "doi-asserted-by": "publisher",
      "first-page": "1826",
      "DOI": "10.1073/pnas.0808843106",
      "article-title": "Scoring diverse cellular morphologies in image-based screens with iterative feedback and machine learning",
      "volume": "106",
      "author": "Jones",
      "year": "2009",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072905032556200_bib45",
      "doi-asserted-by": "publisher",
      "first-page": "377",
      "DOI": "10.1016/S0960-9822(98)70156-3",
      "article-title": "Histone-GFP fusion protein enables sensitive analysis of chromosome dynamics in living mammalian cells",
      "volume": "8",
      "author": "Kanda",
      "year": "1998",
      "journal-title": "Curr. Biol."
    },
    {
      "key": "2023072905032556200_bib46",
      "doi-asserted-by": "publisher",
      "first-page": "85",
      "DOI": "10.1126/science.1165620",
      "article-title": "The automation of science",
      "volume": "324",
      "author": "King",
      "year": "2009",
      "journal-title": "Science."
    },
    {
      "key": "2023072905032556200_bib47",
      "doi-asserted-by": "publisher",
      "first-page": "1401",
      "DOI": "10.1038/ncb1659",
      "article-title": "Genome-scale RNAi profiling of cell division in human tissue culture cells",
      "volume": "9",
      "author": "Kittler",
      "year": "2007",
      "journal-title": "Nat. Cell Biol."
    },
    {
      "key": "2023072905032556200_bib48",
      "doi-asserted-by": "publisher",
      "first-page": "847",
      "DOI": "10.1038/nmeth1089",
      "article-title": "A probability-based approach for the analysis of large-scale RNAi screens",
      "volume": "4",
      "author": "K\u00f6nig",
      "year": "2007",
      "journal-title": "Nat. Methods."
    },
    {
      "key": "2023072905032556200_bib49",
      "doi-asserted-by": "publisher",
      "first-page": "242",
      "DOI": "10.1038/nature07207",
      "article-title": "RNA interference screen for human genes associated with West Nile virus infection",
      "volume": "455",
      "author": "Krishnan",
      "year": "2008",
      "journal-title": "Nature."
    },
    {
      "key": "2023072905032556200_bib50",
      "first-page": "S7",
      "article-title": "Photobleaching and photoactivation: following protein dynamics in living cells",
      "volume": "Suppl",
      "author": "Lippincott-Schwartz",
      "year": "2003",
      "journal-title": "Nat. Cell Biol."
    },
    {
      "key": "2023072905032556200_bib51",
      "doi-asserted-by": "publisher",
      "first-page": "R26",
      "DOI": "10.1186/gb-2009-10-3-r26",
      "article-title": "Parallel RNAi screens across different cell lines identify generic and cell type-specific regulators of actin organization and cell morphology",
      "volume": "10",
      "author": "Liu",
      "year": "2009",
      "journal-title": "Genome Biol."
    },
    {
      "key": "2023072905032556200_bib52",
      "doi-asserted-by": "crossref",
      "first-page": "445",
      "DOI": "10.1038/nmeth1032",
      "article-title": "Image-based multivariate profiling of drug responses from single cells",
      "volume": "4",
      "author": "Loo",
      "year": "2007",
      "journal-title": "Nat. Methods."
    },
    {
      "key": "2023072905032556200_bib53",
      "doi-asserted-by": "publisher",
      "first-page": "784",
      "DOI": "10.1016/j.cell.2007.08.031",
      "article-title": "Imaging in systems biology",
      "volume": "130",
      "author": "Megason",
      "year": "2007",
      "journal-title": "Cell."
    },
    {
      "key": "2023072905032556200_bib54",
      "doi-asserted-by": "publisher",
      "first-page": "343",
      "DOI": "10.1038/nature02873",
      "article-title": "Mechanisms of gene silencing by double-stranded RNA",
      "volume": "431",
      "author": "Meister",
      "year": "2004",
      "journal-title": "Nature."
    },
    {
      "key": "2023072905032556200_bib55",
      "doi-asserted-by": "publisher",
      "first-page": "555",
      "DOI": "10.1016/S0091-679X(08)85024-8",
      "article-title": "Open tools for storage and management of quantitative image data",
      "volume": "85",
      "author": "Moore",
      "year": "2008",
      "journal-title": "Methods Cell Biol."
    },
    {
      "key": "2023072905032556200_bib56",
      "doi-asserted-by": "publisher",
      "first-page": "14819",
      "DOI": "10.1073/pnas.0604320103",
      "article-title": "Genome-wide functional analysis of human cell-cycle regulators",
      "volume": "103",
      "author": "Mukherji",
      "year": "2006",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072905032556200_bib57",
      "doi-asserted-by": "publisher",
      "first-page": "871",
      "DOI": "10.1038/nature03869",
      "article-title": "Identification of JAK/STAT signalling components by genome-wide RNA interference",
      "volume": "436",
      "author": "M\u00fcller",
      "year": "2005",
      "journal-title": "Nature."
    },
    {
      "key": "2023072905032556200_bib58",
      "doi-asserted-by": "publisher",
      "first-page": "385",
      "DOI": "10.1038/nmeth876",
      "article-title": "High-throughput RNAi screening by time-lapse imaging of live human cells",
      "volume": "3",
      "author": "Neumann",
      "year": "2006",
      "journal-title": "Nat. Methods."
    },
    {
      "key": "2023072905032556200_bib59",
      "doi-asserted-by": "crossref",
      "DOI": "10.1038/nature08869",
      "article-title": "Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes",
      "author": "Neumann",
      "year": "2010",
      "journal-title": "Nature."
    },
    {
      "key": "2023072905032556200_bib60",
      "doi-asserted-by": "publisher",
      "first-page": "78",
      "DOI": "10.1038/nature03571",
      "article-title": "Genome-wide analysis of human kinases in clathrin- and caveolae/raft-mediated endocytosis",
      "volume": "436",
      "author": "Pelkmans",
      "year": "2005",
      "journal-title": "Nature."
    },
    {
      "key": "2023072905032556200_bib61",
      "doi-asserted-by": "publisher",
      "first-page": "690",
      "DOI": "10.1038/nrm1979",
      "article-title": "High-throughput fluorescence microscopy for systems biology",
      "volume": "7",
      "author": "Pepperkok",
      "year": "2006",
      "journal-title": "Nat. Rev. Mol. Cell Biol."
    },
    {
      "key": "2023072905032556200_bib62",
      "doi-asserted-by": "publisher",
      "first-page": "1194",
      "DOI": "10.1126/science.1100709",
      "article-title": "Multidimensional drug profiling by automated microscopy",
      "volume": "306",
      "author": "Perlman",
      "year": "2004",
      "journal-title": "Science."
    },
    {
      "key": "2023072905032556200_bib63",
      "doi-asserted-by": "publisher",
      "first-page": "9059",
      "DOI": "10.1073/pnas.0802982105",
      "article-title": "In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen",
      "volume": "105",
      "author": "Plouffe",
      "year": "2008",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072905032556200_bib64",
      "doi-asserted-by": "publisher",
      "first-page": "409",
      "DOI": "10.1038/nmeth.1199",
      "article-title": "BAC TransgeneOmics: a high-throughput method for exploration of protein function in mammals",
      "volume": "5",
      "author": "Poser",
      "year": "2008",
      "journal-title": "Nat. Methods."
    },
    {
      "key": "2023072905032556200_bib65",
      "doi-asserted-by": "publisher",
      "first-page": "438",
      "DOI": "10.1016/1049-9652(92)90027-U",
      "article-title": "A survey of moment-based techniques for unoccluded object representation and recognition",
      "volume": "54",
      "author": "Prokop",
      "year": "1992",
      "journal-title": "CVGIP: Graphical Models and Image Processing."
    },
    {
      "key": "2023072905032556200_bib66",
      "doi-asserted-by": "publisher",
      "first-page": "3028",
      "DOI": "10.1093/bioinformatics/btp524",
      "article-title": "CellClassifier: supervised learning of cellular phenotypes",
      "volume": "25",
      "author": "R\u00e4m\u00f6",
      "year": "2009",
      "journal-title": "Bioinformatics."
    },
    {
      "key": "2023072905032556200_bib67",
      "doi-asserted-by": "publisher",
      "first-page": "715",
      "DOI": "10.1038/nmeth924",
      "article-title": "Genome-scale loss-of-function screening with a lentiviral RNAi library",
      "volume": "3",
      "author": "Root",
      "year": "2006",
      "journal-title": "Nat. Methods."
    },
    {
      "key": "2023072905032556200_bib68",
      "doi-asserted-by": "publisher",
      "first-page": "113",
      "DOI": "10.1007/978-1-60327-993-2_7",
      "article-title": "Automated live microscopy to study mitotic gene function in fluorescent reporter cell lines",
      "volume": "545",
      "author": "Schmitz",
      "year": "2009",
      "journal-title": "Methods Mol. Biol."
    },
    {
      "key": "2023072905032556200_bib69",
      "doi-asserted-by": "publisher",
      "first-page": "620",
      "DOI": "10.1016/S0076-6879(06)14032-X",
      "article-title": "Digital autofocus methods for automated microscopy",
      "volume": "414",
      "author": "Shen",
      "year": "2006",
      "journal-title": "Methods Enzymol."
    },
    {
      "key": "2023072905032556200_bib70",
      "doi-asserted-by": "publisher",
      "first-page": "525",
      "DOI": "10.1038/nmeth892",
      "article-title": "Dynamic proteomics in individual human cells uncovers widespread cell-cycle dependence of nuclear proteins",
      "volume": "3",
      "author": "Sigal",
      "year": "2006",
      "journal-title": "Nat. Methods."
    },
    {
      "key": "2023072905032556200_bib71",
      "doi-asserted-by": "publisher",
      "first-page": "61",
      "DOI": "10.1126/science.1097931",
      "article-title": "Dissection of the mammalian midbody proteome reveals conserved cytokinesis mechanisms",
      "volume": "305",
      "author": "Skop",
      "year": "2004",
      "journal-title": "Science."
    },
    {
      "key": "2023072905032556200_bib72",
      "doi-asserted-by": "publisher",
      "first-page": "520",
      "DOI": "10.1038/nature08282",
      "article-title": "Population context determines cell-to-cell variability in endocytosis and virus infection",
      "volume": "461",
      "author": "Snijder",
      "year": "2009",
      "journal-title": "Nature."
    },
    {
      "key": "2023072905032556200_bib73",
      "doi-asserted-by": "publisher",
      "first-page": "689",
      "DOI": "10.1038/nmeth927",
      "article-title": "Expressing short hairpin RNAs in vivo",
      "volume": "3",
      "author": "Sn\u00f8ve",
      "year": "2006",
      "journal-title": "Nat. Methods."
    },
    {
      "key": "2023072905032556200_bib74",
      "doi-asserted-by": "publisher",
      "first-page": "462",
      "DOI": "10.1038/nature03353",
      "article-title": "Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans",
      "volume": "434",
      "author": "S\u00f6nnichsen",
      "year": "2005",
      "journal-title": "Nature."
    },
    {
      "key": "2023072905032556200_bib75",
      "doi-asserted-by": "publisher",
      "first-page": "473",
      "DOI": "10.1016/j.cell.2008.12.020",
      "article-title": "Aurora B-mediated abscission checkpoint protects against tetraploidization",
      "volume": "136",
      "author": "Steigemann",
      "year": "2009",
      "journal-title": "Cell."
    },
    {
      "key": "2023072905032556200_bib76",
      "doi-asserted-by": "publisher",
      "first-page": "100",
      "DOI": "10.1126/science.1082602",
      "article-title": "Informatics and quantitative analysis in biological imaging",
      "volume": "300",
      "author": "Swedlow",
      "year": "2003",
      "journal-title": "Science."
    },
    {
      "key": "2023072905032556200_bib77",
      "doi-asserted-by": "publisher",
      "first-page": "60",
      "DOI": "10.1016/j.cbpa.2008.01.020",
      "article-title": "Fluorescent biosensors of protein function",
      "volume": "12",
      "author": "VanEngelenburg",
      "year": "2008",
      "journal-title": "Curr. Opin. Chem. Biol."
    },
    {
      "key": "2023072905032556200_bib78",
      "doi-asserted-by": "crossref",
      "first-page": "790",
      "DOI": "10.1109/ICPR.1996.546931",
      "article-title": "Statistical geometric features-extensions for cytological texture analysis",
      "volume": "2",
      "author": "Walker",
      "year": "1996",
      "journal-title": "Proceedings of the 13th International Conference on Pattern Recognition."
    },
    {
      "key": "2023072905032556200_bib79",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/j.jsb.2009.10.004",
      "article-title": "Automatic identification and clustering of chromosome phenotypes in a genome wide RNAi screen by time-lapse imaging",
      "author": "Walter",
      "year": "2009",
      "journal-title": "J. Struct. Biol."
    },
    {
      "key": "2023072905032556200_bib80",
      "doi-asserted-by": "publisher",
      "first-page": "682",
      "DOI": "10.1038/nmeth914",
      "article-title": "Tuning silence: conditional systems for RNA interference",
      "volume": "3",
      "author": "Wiznerowicz",
      "year": "2006",
      "journal-title": "Nat. Methods."
    },
    {
      "key": "2023072905032556200_bib81",
      "doi-asserted-by": "publisher",
      "first-page": "9942",
      "DOI": "10.1073/pnas.152327299",
      "article-title": "Short RNA duplexes produced by hydrolysis with Escherichia coli RNase III mediate effective RNA interference in mammalian cells",
      "volume": "99",
      "author": "Yang",
      "year": "2002",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072905032556200_bib82",
      "doi-asserted-by": "publisher",
      "first-page": "264",
      "DOI": "10.1186/1471-2105-9-264",
      "article-title": "Using iterative cluster merging with improved gap statistics to perform online phenotype discovery in the context of high-throughput RNAi screens",
      "volume": "9",
      "author": "Yin",
      "year": "2008",
      "journal-title": "BMC Bioinformatics."
    },
    {
      "key": "2023072905032556200_bib83",
      "doi-asserted-by": "publisher",
      "first-page": "67",
      "DOI": "10.1177/108705719900400206",
      "article-title": "A simple statistical parameter for use in evaluation and validation of high throughput screening assays",
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