论文标题
从基因表达和组织学图像中预测患者衍生异种移植物中药物反应的数据增强和多模式学习
Data augmentation and multimodal learning for predicting drug response in patient-derived xenografts from gene expressions and histology images
论文作者
论文摘要
患者衍生的异种移植物(PDXS)是临床前药物研究的吸引人的平台,因为与CCL相比,PDX的体内环境有助于保留肿瘤异质性,并且通常更好地模拟癌症患者的药物反应。我们研究了多模式神经网络(MM-NET)和PDX中药物反应预测的数据增强。 MM-NET学会使用药物描述符,基因表达(GE)和组织学全扫描图像(WSI)来预测响应,其中多模式指的是肿瘤特征。我们探讨了与单独使用GE的模型相比,WSI与GE的集成是否可以改善预测。我们使用两种方法来解决有限的响应值:1)均质化药物表示,这些药物表示可以将单药和药物对处理组合到单个数据集中,2)通过切换药物特征的顺序增加药物特征的顺序,使所有药品样品的样本大小增加一倍。这些方法使我们能够将单药和药物对处理结合起来,从而使我们能够在不改变体系结构或数据集的情况下训练多模式和单峰神经网络(NNS)。比较使用GE的三个单峰NN的预测性能,以评估数据增强方法的贡献。使用完整数据集的NN,其中包括原始药物和增强药物治疗以及单药处理明显优于忽略增强药对或单毒处理的NN。在评估基于MCC度量的多模式学习的贡献时,MM-NET在统计上显着优于所有基准。我们的结果表明,组织学图像与GE的数据增强和整合可以改善PDX中药物反应的预测性能。
Patient-derived xenografts (PDXs) are an appealing platform for preclinical drug studies because the in vivo environment of PDXs helps preserve tumor heterogeneity and usually better mimics drug response of patients with cancer compared to CCLs. We investigate multimodal neural network (MM-Net) and data augmentation for drug response prediction in PDXs. The MM-Net learns to predict response using drug descriptors, gene expressions (GE), and histology whole-slide images (WSIs) where the multi-modality refers to the tumor features. We explore whether the integration of WSIs with GE improves predictions as compared with models that use GE alone. We use two methods to address the limited number of response values: 1) homogenize drug representations which allows to combine single-drug and drug-pairs treatments into a single dataset, 2) augment drug-pair samples by switching the order of drug features which doubles the sample size of all drug-pair samples. These methods enable us to combine single-drug and drug-pair treatments, allowing us to train multimodal and unimodal neural networks (NNs) without changing architectures or the dataset. Prediction performance of three unimodal NNs which use GE are compared to assess the contribution of data augmentation methods. NN that uses the full dataset which includes the original and the augmented drug-pair treatments as well as single-drug treatments significantly outperforms NNs that ignore either the augmented drug-pairs or the single-drug treatments. In assessing the contribution of multimodal learning based on the MCC metric, MM-Net statistically significantly outperforms all the baselines. Our results show that data augmentation and integration of histology images with GE can improve prediction performance of drug response in PDXs.