An automated fitting procedure and software for dose-response curves with multiphasic features.
An automated fitting procedure and software for dose-response curves with multiphasic features.
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DOI：
10.1038/srep14701
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发表时间：
2015-10-01
影响因子：
4.6
通讯作者：
Jodrell DI
中科院分区：
文献类型：
--
作者：
Di Veroli GY;Fornari C;Goldlust I;Mills G;Koh SB;Bramhall JL;Richards FM;Jodrell DI
在癌症药理学（和许多其他领域）中，大多数剂量-反应曲线都可以用经典的希尔方程（即4个参数逻辑）令人满意地描述。然而，在某些情况下，明显存在一个以上的拐点，或存在激动剂和拮抗剂的联合作用，阻碍了通过标准希尔方程直接建立数据模型。本文提出了一个改进的模型和自动拟合程序来描述具有多相特征的剂量-响应曲线。由此产生的一般模型能够将剂量反应的每个阶段解释为一个独立的剂量依赖过程。我们开发了一种算法，可以自动生成和排序具有不同程度多相特征的剂量反应模型。该算法在新的免费Dr Fit软件（sourceforge.net/projects/drfit/）中实现。我们展示了我们的方法如何成功地描述具有多相特征的剂量-响应曲线。此外，我们分析了涉及11650个剂量-反应曲线的大型癌细胞活力筛选。根据我们的算法，我们发现28%的病例用多相模型比用希尔模型更好地描述。因此，我们提供了一种健壮的方法来拟合具有不同复杂程度的剂量-反应曲线，与所提供的软件实现一起，应该使广大受众能够轻松地处理他们自己的数据。
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.