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@ARTICLE{Brix:307461,
      author       = {N. Brix and D. Samaga and K. Gehr and B. Dankó and M.
                      Schumann and G. Drexler and A. Alnatsha and G. Beyer and U.
                      Mahajan and M. Selmansberger and J. Mayerle$^*$ and C.
                      Belka$^*$ and H. Zitzelsberger and K. Lauber$^*$},
      title        = {{LDA}coop: {I}ntegrating non-linear population dynamics
                      into the analysis of clonogenic growth in vitro.},
      journal      = {Molecular oncology},
      volume       = {nn},
      issn         = {1574-7891},
      address      = {Hoboken, NJ},
      publisher    = {John Wiley $\&$ Sons, Inc.},
      reportid     = {DKFZ-2025-03060},
      pages        = {nn},
      year         = {2025},
      note         = {epub},
      abstract     = {The limiting dilution assay (LDA) is a key method to
                      quantify clonogenic cells with self-renewing capacity in
                      vitro, crucial for preclinical cancer research and therapy
                      response assessment. It estimates the frequency of
                      individual clonogenic, stem-like cells within a population
                      based on their ability to form colonies with ≥50 cells at
                      limiting cell numbers. Standard LDA analysis relies on
                      linear, single-hit Poisson models, yet clonogenic growth
                      under single-cell conditions often involves cooperative or
                      competitive dynamics, violating this linearity assumption.
                      Here, we present a modeling framework incorporating
                      non-linear population dynamics into LDA analysis and
                      introduce LDAcoop, an R-based tool for universal
                      quantification of clonogenic cells in LDA formats. Across
                      multiple cancer cell types, we benchmarked LDA against the
                      colony formation assay (CFA) and show that LDA outperforms
                      CFA, especially for patient-derived organoids, suspension
                      cultures, and higher throughput applications. This renders
                      the LDA format particularly suitable for larger-scale
                      pharmacogenomic screening and drug sensitivity testing in
                      complex models. Our results establish LDA and LDAcoop as
                      versatile, scalable tools for robust quantification of
                      clonogenic growth, supporting preclinical drug development
                      and molecular precision oncology research.},
      keywords     = {Allee effect (Other) / cellular competition (Other) /
                      cellular cooperation (Other) / clonogenic growth (Other) /
                      clonogenic survival (Other) / limiting dilution assay
                      (Other)},
      cin          = {MU01},
      ddc          = {610},
      cid          = {I:(DE-He78)MU01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41454442},
      doi          = {10.1002/1878-0261.70185},
      url          = {https://inrepo02.dkfz.de/record/307461},
}