School of Computer Science and Technology, Heilongjiang University, Harbin 150080, China.
School of Mathematical Science, Heilongjiang University, Harbin 150080, China.
Molecules. 2019 Jul 25;24(15):2712. doi: 10.3390/molecules24152712.
Predicting novel uses for drugs using their chemical, pharmacological, and indication information contributes to minimizing costs and development periods. Most previous prediction methods focused on integrating the similarity and association information of drugs and diseases. However, they tended to construct shallow prediction models to predict drug-associated diseases, which make deeply integrating the information difficult. Further, path information between drugs and diseases is important auxiliary information for association prediction, while it is not deeply integrated. We present a deep learning-based method, CGARDP, for predicting drug-related candidate disease indications. CGARDP establishes a feature matrix by exploiting a variety of biological premises related to drugs and diseases. A novel model based on convolutional neural network (CNN) and gated recurrent unit (GRU) is constructed to learn the local and path representations for a drug-disease pair. The CNN-based framework on the left of the model learns the local representation of the drug-disease pair from their feature matrix. As the different paths have discriminative contributions to the drug-disease association prediction, we construct an attention mechanism at the path level to learn the informative paths. In the right part, a GRU-based framework learns the path representation based on path information between the drug and the disease. Cross-validation results indicate that CGARDP performs better than several state-of-the-art methods. Further, CGARDP retrieves more real drug-disease associations in the top part of the prediction result that are of concern to biologists. Case studies on five drugs demonstrate that CGARDP can discover potential drug-related disease indications.
利用药物的化学、药理学和适应证信息来预测新的用途有助于最大限度地降低成本和开发周期。大多数先前的预测方法都侧重于整合药物和疾病的相似性和关联性信息。然而,它们往往构建浅层预测模型来预测与药物相关的疾病,这使得难以深入整合信息。此外,药物和疾病之间的路径信息是关联预测的重要辅助信息,但它没有得到深入整合。我们提出了一种基于深度学习的方法 CGARDP,用于预测药物相关的候选疾病适应证。CGARDP 通过利用与药物和疾病相关的多种生物学前提来建立特征矩阵。基于卷积神经网络(CNN)和门控循环单元(GRU)的新型模型被构建来学习药物-疾病对的局部和路径表示。模型左侧基于 CNN 的框架从特征矩阵中学习药物-疾病对的局部表示。由于不同的路径对药物-疾病关联预测有判别性贡献,我们构建了一个注意力机制来学习有信息的路径。在右侧,基于 GRU 的框架基于药物和疾病之间的路径信息学习路径表示。交叉验证结果表明,CGARDP 优于几种最先进的方法。此外,CGARDP 在预测结果的前半部分检索到更多生物学家关注的真实药物-疾病关联。对五种药物的案例研究表明,CGARDP 可以发现潜在的药物相关疾病适应证。