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@ARTICLE{Carraro:165276,
      author       = {Carraro, Caterina and Bonaguro, Lorenzo and
                      Schulte-Schrepping, Jonas and Horne, Arik and Oestreich,
                      Marie and Warnat-Herresthal, Stefanie and Helbing, Tim and
                      De Franco, Michele and Händler, Kristian and Mukherjee,
                      Sach and Ulas, Thomas and Gandin, Valentina and Goettlich,
                      Richard and Aschenbrenner, Anna Christin and Schultze,
                      Joachim L and Gatto, Barbara},
      title        = {{D}ecoding mechanism of action and sensitivity to drug
                      candidates from integrated transcriptome and chromatin
                      state.},
      journal      = {eLife},
      volume       = {11},
      issn         = {2050-084X},
      address      = {Cambridge},
      publisher    = {eLife Sciences Publications},
      reportid     = {DZNE-2022-01569},
      pages        = {e78012},
      year         = {2022},
      note         = {CC BY: https://creativecommons.org/licenses/by/4.0/},
      abstract     = {Omics-based technologies are driving major advances in
                      precision medicine, but efforts are still required to
                      consolidate their use in drug discovery. In this work, we
                      exemplify the use of multi-omics to support the development
                      of 3-chloropiperidines, a new class of candidate anticancer
                      agents. Combined analyses of transcriptome and chromatin
                      accessibility elucidated the mechanisms underlying
                      sensitivity to test agents. Furthermore, we implemented a
                      new versatile strategy for the integration of RNA- and
                      ATAC-seq (Assay for Transposase-Accessible Chromatin) data,
                      able to accelerate and extend the standalone analyses of
                      distinct omic layers. This platform guided the construction
                      of a perturbation-informed basal signature predicting cancer
                      cell lines' sensitivity and to further direct compound
                      development against specific tumor types. Overall, this
                      approach offers a scalable pipeline to support the early
                      phases of drug discovery, understanding of mechanisms, and
                      potentially inform the positioning of therapeutics in the
                      clinic.},
      keywords     = {Chromatin / Precision Medicine / RNA / Transcriptome /
                      Transposases: metabolism / chromatin accessibility (Other) /
                      computational biology (Other) / drug candidate (Other) /
                      human (Other) / mechanism of action (Other) / multi-omics
                      (Other) / sensitivity ML prediction (Other) / systems
                      biology (Other) / transcriptome (Other) / Chromatin (NLM
                      Chemicals) / RNA (NLM Chemicals) / Transposases (NLM
                      Chemicals)},
      cin          = {AG Schultze / $R\&D$ PRECISE / AG Mukherjee},
      ddc          = {600},
      cid          = {I:(DE-2719)1013031 / I:(DE-2719)5000031 /
                      I:(DE-2719)1013030},
      pnm          = {352 - Disease Mechanisms (POF4-352) / 354 - Disease
                      Prevention and Healthy Aging (POF4-354)},
      pid          = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-354},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36043458},
      pmc          = {pmc:PMC9433094},
      doi          = {10.7554/eLife.78012},
      url          = {https://pub.dzne.de/record/165276},
}