Journal Article

DKFZ-2025-03060

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png LDAcoop: Integrating non-linear population dynamics into the analysis of clonogenic growth in vitro.

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

2025
John Wiley & Sons, Inc. Hoboken, NJ

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.

Keyword(s): Allee effect ; cellular competition ; cellular cooperation ; clonogenic growth ; clonogenic survival ; limiting dilution assay

Note: epub

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Contributing Institute(s):

1. DKTK Koordinierungsstelle München (MU01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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Database coverage:
; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DEAL Wiley ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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