Fig. 4: Comparison of GR, NDR, and NOGR metrics and their performance in fast- and slow-growing organoids.

A Simulated growth rate response metrics (GR, NDR, and NOGR) plotted against growth rate ranges from 0 to 1.5 to mimic drug response (i.e., reduction in growth rate) in slow-growing organoids. The red and green vertical dashed lines represent the growth rates of the positive and negative controls, respectively. The vertical blue dashed line marks a growth rate of 1, the cutoff between cytostatic (> 1) and cytotoxic (< 1) drug responses. The NDR metric overestimates cytotoxicity (NDR < 0), as an NDR value of -1 is already obtained at a growth rate of around 0.75 instead of 0.3 (positive control). B Growth rate metrics plotted against growth rates ranging from 0 to 8, representing fast-growing organoids. The GR metric underestimates cytotoxicity (GR < 0) due to the lack of positive control normalization, while the NDR metric underestimates the cytostatic effect (1 > NDR > 0) due to its logarithmic fit. C Comparison of NOGR vs. NDR values for a panel of 10 PDAC organoids treated with a concentration range of five chemotherapeutics for 72 h. Each data point represents an individual concentration, chemotherapeutic, and organoid, with the color legend indicating the corresponding organoid line and its growth rate. D Comparison of NOGR vs. GR values for the same panel of PDAC organoids at 72 h. The scatter plot shows the relationship between the two metrics for different concentrations of the tested chemotherapeutics and organoid lines.