Estimating dose-specific cell division and apoptosis rates from chemo-sensitivity experiments.
Estimating dose-specific cell division and apoptosis rates from chemo-sensitivity experiments.
复制标题
通过化学敏感性实验估计剂量特异性细胞分裂和凋亡率。
DOI：
10.1038/s41598-018-21017-5
复制
发表时间：
2018
影响因子：
4.6
通讯作者：
Crawford,ForrestW
中科院分区：
文献类型：
--
作者：
Liu,Yiyi;Crawford,ForrestW
体外化疗敏感性实验是癌症治疗发展的早期阶段必不可少的一步，但现有的数据分析方法存在拟合问题，不允许评估不确定性，并且可能对细胞生长抑制给出误导性的估计。我们提出了一种基于细胞分裂和死亡的机制模型的方法(BdChemo)，该方法允许通过同时估计细胞分裂和凋亡率作为剂量的函数来对化疗敏感性实验数据进行严格的统计分析，而不会对剂量-反应曲线的形状做出强烈的假设。我们使用一个大规模的NCI-DREAM挑战数据集演示了该方法的实用性。我们开发了一个实现此方法的R包“bdChemo”，可从https://github.com/YiyiLiu1/bdChemo.获得
In-vitrochemo-sensitivity experiments are an essential step in the early stages of cancer therapy development, but existing data analysis methods suffer from problems with fitting, do not permit assessment of uncertainty, and can give misleading estimates of cell growth inhibition. We present an approach (bdChemo) based on a mechanistic model of cell division and death that permits rigorous statistical analyses of chemo-sensitivity experiment data by simultaneous estimation of cell division and apoptosis rates as functions of dose, without making strong assumptions about the shape of the dose-response curve. We demonstrate the utility of this method using a large-scale NCI-DREAM challenge dataset. We developed an R package “bdChemo” implementing this method, available at https://github.com/YiyiLiu1/bdChemo.