论文标题

合奏转移学习预测抗癌药物反应

Ensemble Transfer Learning for the Prediction of Anti-Cancer Drug Response

论文作者

Zhu, Yitan, Brettin, Thomas, Evrard, Yvonne A., Partin, Alexander, Xia, Fangfang, Shukla, Maulik, Yoo, Hyunseung, Doroshow, James H., Stevens, Rick

论文摘要

在许多应用程序中,转移学习已被证明是有效的,在许多应用中,目标问题的培训数据有限,但相关(源)问题的数据很丰富。在本文中,我们将转移学习应用于抗癌药物反应的预测。对药物反应预测的先前转移学习研究集中在预测肿瘤细胞对特定药物治疗的反应的建筑模型上。我们针对建立一般预测模型的更具挑战性的任务,该模型可以对新的肿瘤细胞和新药物进行预测。我们应用了经典的传输学习框架,该框架在源数据集上训练预测模型并在目标数据集中完善它,并通过集合扩展框架。使用LightGBM和具有不同体系结构的两个深神经网络(DNN)模型实现集合转移学习管道。独特的是,我们通过交叉验证中的不同数据分区方案研究了其在三种应用程序环境中的功能,包括药物重新利用,精度肿瘤学和新药物开发。我们在体外药物筛选数据集上测试了基准上提出的集合转移学习,将一个数据集作为源域,另一个数据集作为目标域。分析结果表明,应用集合转移学习以在所有三种应用中都使用LightGBM和DNN模型中预测抗癌药物反应的好处。比较不同的预测模型,一个具有两个子网的DNN模型,用于肿瘤特征的输入和药物特征分别优于LightGBM和其他DNN模型,该模型将肿瘤特征和药物特征连接起来,以在药物重新培训和精确肿瘤学应用中输入。在新药开发的更具挑战性的应用中,LightGBM的性能比其他两个DNN模型更好。

Transfer learning has been shown to be effective in many applications in which training data for the target problem are limited but data for a related (source) problem are abundant. In this paper, we apply transfer learning to the prediction of anti-cancer drug response. Previous transfer learning studies for drug response prediction focused on building models that predict the response of tumor cells to a specific drug treatment. We target the more challenging task of building general prediction models that can make predictions for both new tumor cells and new drugs. We apply the classic transfer learning framework that trains a prediction model on the source dataset and refines it on the target dataset, and extends the framework through ensemble. The ensemble transfer learning pipeline is implemented using LightGBM and two deep neural network (DNN) models with different architectures. Uniquely, we investigate its power for three application settings including drug repurposing, precision oncology, and new drug development, through different data partition schemes in cross-validation. We test the proposed ensemble transfer learning on benchmark in vitro drug screening datasets, taking one dataset as the source domain and another dataset as the target domain. The analysis results demonstrate the benefit of applying ensemble transfer learning for predicting anti-cancer drug response in all three applications with both LightGBM and DNN models. Compared between the different prediction models, a DNN model with two subnetworks for the inputs of tumor features and drug features separately outperforms LightGBM and the other DNN model that concatenates tumor features and drug features for input in the drug repurposing and precision oncology applications. In the more challenging application of new drug development, LightGBM performs better than the other two DNN models.

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