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@ARTICLE{RosendahlHuber:288881,
      author       = {A. Rosendahl Huber and C. Pleguezuelos-Manzano and J.
                      Puschhof$^*$ and J. Ubels and C. Boot and A. Saftien$^*$ and
                      M. Verheul and L. T. Trabut and N. Groenen and M. van
                      Roosmalen and K. S. Ouyang$^*$ and H. Wood and P. Quirke and
                      G. Meijer and E. Cuppen and H. Clevers and R. van Boxtel},
      title        = {{I}mproved detection of colibactin-induced mutations by
                      genotoxic {E}. coli in organoids and colorectal cancer.},
      journal      = {Cancer cell},
      volume       = {42},
      number       = {3},
      issn         = {1535-6108},
      address      = {New York, NY},
      publisher    = {Elsevier},
      reportid     = {DKFZ-2024-00523},
      pages        = {487 - 496.e6},
      year         = {2024},
      abstract     = {Co-culture of intestinal organoids with a
                      colibactin-producing pks+E. coli strain (EcC) revealed
                      mutational signatures also found in colorectal cancer (CRC).
                      E. coli Nissle 1917 (EcN) remains a commonly used probiotic,
                      despite harboring the pks operon and inducing double strand
                      DNA breaks. We determine the mutagenicity of EcN and three
                      CRC-derived pks+E. coli strains with an analytical framework
                      based on sequence characteristic of colibactin-induced
                      mutations. All strains, including EcN, display varying
                      levels of mutagenic activity. Furthermore, a machine
                      learning approach attributing individual mutations to
                      colibactin reveals that patients with colibactin-induced
                      mutations are diagnosed at a younger age and that colibactin
                      can induce a specific APC mutation. These approaches allow
                      the sensitive detection of colibactin-induced mutations in
                      $∼12\%$ of CRC genomes and even in whole exome sequencing
                      data, representing a crucial step toward pinpointing the
                      mutagenic activity of distinct pks+E. coli strains.},
      keywords     = {bacteria (Other) / cancer genomics (Other) / colibactin
                      (Other) / colorectal cancer (Other) / genotoxins (Other) /
                      machine learning (Other) / mutagenesis (Other) / mutational
                      signatures (Other) / organoids (Other) / probiotics (Other)},
      cin          = {F220 / D480},
      ddc          = {610},
      cid          = {I:(DE-He78)F220-20160331 / I:(DE-He78)D480-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38471458},
      doi          = {10.1016/j.ccell.2024.02.009},
      url          = {https://inrepo02.dkfz.de/record/288881},
}