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gene, cell, dependency, genes, data, lines, estimates, fig, model, rnai, effects, datasets, achilles, dataset, shrna, line, differences, methods, dependencies, average, article, parameters, drive, correlation, essential, cancer, compared, number, screen, relationships, supplementary, screens, demeter, combined, expression, shrnas, quality, scores, models, google, scholar, genetic, relative, sigma, analysis, nature, correlations, copy, estimated, common,

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         description:The availability of multiple datasets comprising genome-scale RNAi viability screens in hundreds of diverse cancer cell lines presents new opportunities for understanding cancer vulnerabilities. Integrated analyses of these data to assess differential dependency across genes and cell lines are challenging due to confounding factors such as batch effects and variable screen quality, as well as difficulty assessing gene dependency on an absolute scale. To address these issues, we incorporated cell line screen-quality parameters and hierarchical Bayesian inference into DEMETER2, an analytical framework for analyzing RNAi screens ( https://depmap.org/R2-D2 ). This model substantially improves estimates of gene dependency across a range of performance measures, including identification of gold-standard essential genes and agreement with CRISPR/Cas9-based viability screens. It also allows us to integrate information across three large RNAi screening datasets, providing a unified resource representing the most extensive compilation of cancer cell line genetic dependencies to date. Integrated analyses of multiple large-scale screenings can be complicated by batch effects and technical artefacts. McFarland et al. introduce DEMETER2, a hierarchical model coupled with model-based normalization, which allows the assessment of differential dependencies across genes and cell lines.
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            name:Dana-Farber Cancer Institute
            address:
               name:Dana-Farber Cancer Institute, Boston, USA
               type:PostalAddress
            type:Organization
      name:Jesse S. Boehm
      url:http://orcid.org/0000-0002-6795-6336
      affiliation:
            name:Broad Institute of MIT and Harvard
            address:
               name:Broad Institute of MIT and Harvard, Cambridge, USA
               type:PostalAddress
            type:Organization
      name:Todd R. Golub
      url:http://orcid.org/0000-0003-0113-2403
      affiliation:
            name:Broad Institute of MIT and Harvard
            address:
               name:Broad Institute of MIT and Harvard, Cambridge, USA
               type:PostalAddress
            type:Organization
            name:Dana-Farber Cancer Institute
            address:
               name:Dana-Farber Cancer Institute, Boston, USA
               type:PostalAddress
            type:Organization
            name:Harvard Medical School
            address:
               name:Harvard Medical School, Boston, USA
               type:PostalAddress
            type:Organization
            name:Boston Children’s Hospital
            address:
               name:Boston Children’s Hospital, Boston, USA
               type:PostalAddress
            type:Organization
            name:Howard Hughes Medical Institute
            address:
               name:Howard Hughes Medical Institute, Chevy Chase, USA
               type:PostalAddress
            type:Organization
      name:William C. Hahn
      url:http://orcid.org/0000-0003-2840-9791
      affiliation:
            name:Broad Institute of MIT and Harvard
            address:
               name:Broad Institute of MIT and Harvard, Cambridge, USA
               type:PostalAddress
            type:Organization
            name:Dana-Farber Cancer Institute
            address:
               name:Dana-Farber Cancer Institute, Boston, USA
               type:PostalAddress
            type:Organization
            name:Harvard Medical School
            address:
               name:Harvard Medical School, Boston, USA
               type:PostalAddress
            type:Organization
            name:Brigham and Women’s Hospital
            address:
               name:Department of Medicine, Brigham and Women’s Hospital, Boston, USA
               type:PostalAddress
            type:Organization
      name:David E. Root
      affiliation:
            name:Broad Institute of MIT and Harvard
            address:
               name:Broad Institute of MIT and Harvard, Cambridge, USA
               type:PostalAddress
            type:Organization
      name:Aviad Tsherniak
      url:http://orcid.org/0000-0002-3797-1877
      affiliation:
            name:Broad Institute of MIT and Harvard
            address:
               name:Broad Institute of MIT and Harvard, Cambridge, USA
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Broad Institute of MIT and Harvard, Cambridge, USA
      name:Broad Institute of MIT and Harvard, Cambridge, USA
      name:Broad Institute of MIT and Harvard, Cambridge, USA
      name:Broad Institute of MIT and Harvard, Cambridge, USA
      name:Broad Institute of MIT and Harvard, Cambridge, USA
      name:Broad Institute of MIT and Harvard, Cambridge, USA
      name:Broad Institute of MIT and Harvard, Cambridge, USA
      name:Broad Institute of MIT and Harvard, Cambridge, USA
      name:Broad Institute of MIT and Harvard, Cambridge, USA
      name:Dana-Farber Cancer Institute, Boston, USA
      name:Broad Institute of MIT and Harvard, Cambridge, USA
      name:Broad Institute of MIT and Harvard, Cambridge, USA
      name:Dana-Farber Cancer Institute, Boston, USA
      name:Harvard Medical School, Boston, USA
      name:Boston Children’s Hospital, Boston, USA
      name:Howard Hughes Medical Institute, Chevy Chase, USA
      name:Broad Institute of MIT and Harvard, Cambridge, USA
      name:Dana-Farber Cancer Institute, Boston, USA
      name:Harvard Medical School, Boston, USA
      name:Department of Medicine, Brigham and Women’s Hospital, Boston, USA
      name:Broad Institute of MIT and Harvard, Cambridge, USA
      name:Broad Institute of MIT and Harvard, Cambridge, USA

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