Journal Article

An automated fitting procedure and software for dose-response curves with multiphasic features

Koh, Siang Boon, Goldlust, Ian, Richards, Frances M., Jodrell, Duncan I., Mills, Graham, Fornari, Chiara, Bramhall, Jo L, Di Veroli, Giovanni Y.

2015

Overview

In cancer pharmacology (and many other areas), most dose-response curves are satisfactorily described by a classical Hill equation (i.e. 4 parameters logistical). Nevertheless, there are instances where the marked presence of more than one point of inflection, or the presence of combined agonist and antagonist effects, prevents straight-forward modelling of the data via a standard Hill equation. Here we propose a modified model and automated fitting procedure to describe dose-response curves with multiphasic features. The resulting general model enables interpreting each phase of the dose-response as an independent dose-dependent process. We developed an algorithm which automatically generates and ranks dose-response models with varying degrees of multiphasic features. The algorithm was implemented in new freely available Dr Fit software (sourceforge.net/projects/drfit/). We show how our approach is successful in describing dose-response curves with multiphasic features. Additionally, we analysed a large cancer cell viability screen involving 11650 dose-response curves. Based on our algorithm, we found that 28% of cases were better described by a multiphasic model than by the Hill model. We thus provide a robust approach to fit dose-response curves with various degrees of complexity, which, together with the provided software implementation, should enable a wide audience to easily process their own data.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13 / 631/114/1314 / 631/67/1059 / 631/92/436 / Algorithms / Automation / Cancer / Computer programs / Dose-Response Relationship, Drug / Humanities and Social Sciences / Humans / Models, Theoretical / multidisciplinary / Pharmacology / Science / Software