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Brix, N.* ; Samaga, D. ; Gehr, K.* ; Danko, B. ; Schumann, M.* ; Drexler, G.* ; Alnatsha, A.* ; Beyer, G.* ; Mahajan, U.* ; Selmansberger, M. ; Mayerle, J.* ; Belka, C.* ; Zitzelsberger, H. ; Lauber, K.*

LDAcoop: Integrating non-linear population dynamics into the analysis of clonogenic growth in vitro.

Mol. Oncol., DOI: 10.1002/1878-0261.70185 (2025)
Publ. Version/Full Text Postprint Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Allee Effect ; Cellular Competition ; Cellular Cooperation ; Clonogenic Growth ; Clonogenic Survival ; Limiting Dilution Assay; Limiting Dilution Assays; Colony Formation; Mammalian Cells; Tumor; Culture
ISSN (print) / ISBN 1574-7891
e-ISSN 1878-0261
Journal Molecular Oncology
Publisher Wiley
Publishing Place Amsterdam [u.a.]
Reviewing status Peer reviewed
Institute(s) Translational Metabolic Oncology (IDC-TMO)
Grants Deutsche Forschungsgemeinschaft
Bundesministerium fr Bildung und Forschung