VUScope: a mathematical model for evaluating image-based drug response measurements and predicting long-term incubation outcomes

Abstract Motivation Live-cell imaging-based drug screening increases the likelihood of identifying effective and safe drugs by providing dynamic, high-content, and physiologically relevant data. As a result, it improves the success rate of drug development and facilitates the translation of benchside discoveries to bedside applications. Despite these advantages, no comprehensive metrics currently exist to evaluate dose-time-dependent drug responses. To address this gap, we established a systematic framework to assess drug effects across a range of concentrations and exposure durations simultaneously. This metric enables more accurate evaluation of drug responses measured by live-cell imaging. Results We employed treatment concentrations ranging from 0 to 10 μM and performed live-cell imaging-based measurements over a 120-hour incubation period. To analyze the experimental data, we developed VUScope, a new mathematical model combining the 4-parameter logistic curve and a logistic function to characterize dose-time-dependent responses. This enabled us to calculate the Growth Rate Inhibition Volume Under the dose-time-response Surface (GRIVUS), which serves as a critical metric for assessing dynamic drug responses. Furthermore, our mathematical model allowed us to predict long-term treatment responses based on short-term drug responses. We validated the predictive capabilities of our model using independent datasets and observed that VUScope enhances prediction accuracy and offers deeper insights into drug effects than previously possible. By integrating VUScope into high-throughput drug screening platforms, we can further improve the efficacy of drug development and treatment selection. Availability and Implementation We have made VUScope more accessible to users conducting pharmacological studies by uploading a detailed description, example datasets, and the source code to vuscope.albi.hhu.de, https://github.com/AlBi-HHU/VUScope, and https://doi.org/10.5281/zenodo.17610533. Supplementary Information A: Time-independence of GR metrics; B: Key resources; C, D, E: Supplementary figures; F: Modeling choices.