Enhancing the drug discovery process: Bayesian inference for the analysis and comparison of dose–response experiments

Abstract

Abstract Motivation The efficacy of a chemical compound is often tested through dose–response experiments from which efficacy metrics, such as the IC50, can be derived. The Marquardt–Levenberg algorithm (non-linear regression) is commonly used to compute estimations for these metrics. The analysis are however limited and can lead to biased conclusions. The approach does not evaluate the certainty (or uncertainty) of the estimates nor does it allow for the statistical comparison of two datasets. To compensate for these shortcomings, intuition plays an important role in the interpretation of results and the formulations of conclusions. We here propose a Bayesian inference methodology for the analysis and comparison of dose–response experiments. Results Our results well demonstrate the informativeness gain of our Bayesian approach in comparison to the commonly used Marquardt–Levenberg algorithm. It is capable to characterize the noise of dataset while inferring probable values distributions for the efficacy metrics. It can also evaluate the difference between the metrics of two datasets and compute the probability that one value is greater than the other. The conclusions that can be drawn from such analyzes are more precise. Availability and implementation We implemented a simple web interface that allows the users to analyze a single dose–response dataset, as well as to statistically compare the metrics of two datasets.