论文标题
在癌细胞系中的药物反应预测的学习曲线
Learning Curves for Drug Response Prediction in Cancer Cell Lines
论文作者
论文摘要
受细胞系药物敏感性数据的大小的激励,研究人员一直在开发机器学习(ML)模型,以预测药物反应以促进癌症治疗。随着药物敏感性研究继续生成数据,一个常见的问题是,提出的预测因素是否可以通过更多的训练数据进一步改善概括性能。我们利用经验学习曲线评估和比较两个神经网络(NNS)的数据缩放特性和在四个药物筛查数据集中训练的两个梯度增强决策树(GBDT)模型。学习曲线准确地拟合到幂律模型,为评估这些预测变量的数据扩展行为提供了一个框架。曲线表明,没有任何单个模型在所有数据集和训练大小的预测性能方面都占主导地位,这表明这些曲线的形状取决于唯一的模型数据集对。多输入NN(MNN),其中基因表达和分子药物描述符被输入单独的子网,在该子网中优于单输入NN(SNN),将细胞和药物特征置于输入层。相比之下,与两个数据集的两个NNS相比,具有高参数调谐的GBDT表现出较高的性能,而MNN在较高的训练范围内的性能更好。此外,曲线的轨迹表明,增加样本量有望进一步改善两个NNS的预测得分。这些观察结果证明了使用学习曲线评估预测因子的好处,从而对整体数据扩展特征提供了更广泛的观点。拟合的功率定律曲线提供了前瞻性的性能指标,并可以作为指导实验生物学家和计算科学家在未来实验设计中的共同设计工具。
Motivated by the size of cell line drug sensitivity data, researchers have been developing machine learning (ML) models for predicting drug response to advance cancer treatment. As drug sensitivity studies continue generating data, a common question is whether the proposed predictors can further improve the generalization performance with more training data. We utilize empirical learning curves for evaluating and comparing the data scaling properties of two neural networks (NNs) and two gradient boosting decision tree (GBDT) models trained on four drug screening datasets. The learning curves are accurately fitted to a power law model, providing a framework for assessing the data scaling behavior of these predictors. The curves demonstrate that no single model dominates in terms of prediction performance across all datasets and training sizes, suggesting that the shape of these curves depends on the unique model-dataset pair. The multi-input NN (mNN), in which gene expressions and molecular drug descriptors are input into separate subnetworks, outperforms a single-input NN (sNN), where the cell and drug features are concatenated for the input layer. In contrast, a GBDT with hyperparameter tuning exhibits superior performance as compared with both NNs at the lower range of training sizes for two of the datasets, whereas the mNN performs better at the higher range of training sizes. Moreover, the trajectory of the curves suggests that increasing the sample size is expected to further improve prediction scores of both NNs. These observations demonstrate the benefit of using learning curves to evaluate predictors, providing a broader perspective on the overall data scaling characteristics. The fitted power law curves provide a forward-looking performance metric and can serve as a co-design tool to guide experimental biologists and computational scientists in the design of future experiments.