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@ARTICLE{Rauscher:132560,
      author       = {B. G. Rauscher$^*$ and F. Heigwer$^*$ and L. Henkel$^*$ and
                      T. Hielscher$^*$ and O. Voloshanenko$^*$ and M. Boutros$^*$},
      title        = {{T}oward an integrated map of genetic interactions in
                      cancer cells.},
      journal      = {Molecular systems biology},
      volume       = {14},
      number       = {2},
      issn         = {1744-4292},
      address      = {Heidelberg},
      publisher    = {EMBO Press},
      reportid     = {DKFZ-2018-00238},
      pages        = {e7656},
      year         = {2018},
      abstract     = {Cancer genomes often harbor hundreds of molecular
                      aberrations. Such genetic variants can be drivers or
                      passengers of tumorigenesis and create vulnerabilities for
                      potential therapeutic exploitation. To identify
                      genotype-dependent vulnerabilities, forward genetic screens
                      in different genetic backgrounds have been conducted. We
                      devised MINGLE, a computational framework to integrate
                      CRISPR/Cas9 screens originating from different libraries
                      building on approaches pioneered for genetic network
                      discovery in model organisms. We applied this method to
                      integrate and analyze data from 85 CRISPR/Cas9 screens in
                      human cancer cells combining functional data with
                      information on genetic variants to explore more than
                      2.1 million gene-background relationships. In addition to
                      known dependencies, we identified new genotype-specific
                      vulnerabilities of cancer cells. Experimental validation of
                      predicted vulnerabilities identified GANAB and PRKCSH as new
                      positive regulators of Wnt/β-catenin signaling. By
                      clustering genes with similar genetic interaction profiles,
                      we drew the largest genetic network in cancer cells to date.
                      Our scalable approach highlights how diverse genetic screens
                      can be integrated to systematically build informative maps
                      of genetic interactions in cancer, which can grow
                      dynamically as more data are included.},
      cin          = {B110 / C060},
      ddc          = {570},
      cid          = {I:(DE-He78)B110-20160331 / I:(DE-He78)C060-20160331},
      pnm          = {312 - Functional and structural genomics (POF3-312)},
      pid          = {G:(DE-HGF)POF3-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:29467179},
      pmc          = {pmc:PMC5820685},
      doi          = { DOI: 10.15252/msb.20177656 },
      url          = {https://inrepo02.dkfz.de/record/132560},
}