Fig. 5: Drug combination evaluation using CombPDX, invivoSyn, and SynergyLMM. | Nature Communications

Fig. 5: Drug combination evaluation using CombPDX, invivoSyn, and SynergyLMM.

From: Improved analysis of in vivo drug combination experiments with a comprehensive statistical framework and web-tool

Fig. 5

a Tumor growth in Cetuximab + Palbociclib combination experiment in the colon PDX CR1197 model. Each curve corresponds to an individual mouse: vehicle n = 10, Cetuximab n = 8, Palbociclib n = 9, Palbociclib + Cetuximab n = 10. The bold lines in the plots represent the fitted regression lines for the fixed effects of each treatment estimated by the linear mixed-effects model. The x-axis of the plots represents the original time in square-root scale. b Comparison of Bliss synergy evaluation using invivoSyn and SynergyLMM. The horizontal dashed line indicates the combination index threshold of 1 to assess synergy and antagonism. The vertical lines indicate the 95% confidence intervals for the combination index. c, d Evaluation of GABA + anti-PD1 combination effect on tumor growth in 4T1 breast cancer model. Each curve corresponds to an individual mouse: control n = 10, GABA n = 10, anti-PD1 n = 10, GABA + anti-PD1 n = 11. e, f Evaluation of combination Rabusertib + Irinotecan in SW837 colon cancer model. Each curve corresponds to an individual mouse: control n = 6, Rabusertib n = 6, Irinotecan n = 8, Rabusertib + Irinotecan n = 4. c, e display tumor growth data for the different drug combinations across the distinct cancer models. The bold lines in the right plots represent the fitted regression lines for the fixed effects of each treatment estimated by the linear mixed-effects models. The x-axis of the plot in (c) represents the original time in square-root scale. The synergy evaluation using CombPDX, invivoSyn, and SynergyLMM for 4T1 (d) and SW837 (f) tumor models. The horizontal dashed lines indicate the synergy score threshold of 0 to assess synergy and antagonism. The error bars indicate the 95% confidence intervals for the synergy score. The dot in the center indicates the estimated synergy score value. The dot colors in (b) indicate the non-adjusted p values for the one-sided tests from invivoSyn and the two-sided tests from SynergyLMM. The non-adjusted p values reported in (d) and (f) correspond to the one-sided tests from CombPDX and invivoSyn, and two-sided tests from SynergyLMM. HSA highest single agent. Source data are provided as a Source data file.

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