| Autor: |
Giovanni Y, Di Veroli, Chiara, Fornari, Ian, Goldlust, Graham, Mills, Siang Boon, Koh, Jo L, Bramhall, Frances M, Richards, Duncan I, Jodrell |
| Rok vydání: |
2015 |
| Předmět: |
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| Zdroj: |
Scientific Reports |
| ISSN: |
2045-2322 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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