论文标题
DR-COVID:用于SARS-COV-2药物重新使用的图形神经网络
Dr-COVID: Graph Neural Networks for SARS-CoV-2 Drug Repurposing
论文作者
论文摘要
2019年的小说冠状病毒(SARS-COV-2)大流行导致全球超过100万人死亡,高病毒和经济困扰。迫切需要确定可以治疗和预防新型疾病(例如2019年冠状病毒疾病(Covid-19))的药物。与新药物设计和发现相比,由于在成本,安全因素和迅速结果方面的几个优点,毒品重新定位是一项有前途的策略,可以发现现有批准的药物的新医学迹象。在这项工作中,我们探讨了用于重新利用药物的计算数据驱动方法,并提出了一个专用的基于图形神经网络(GNN)的药物重新利用模型,称为DR-Covid。尽管我们分析了Covid-19的预测药物,但该模型是通用的,可用于任何新型疾病。我们构建了一个四层异质图,以模拟药物,疾病,基因和解剖学之间的复杂相互作用。我们将药物重新定位为链接预测问题。具体而言,我们根据可伸缩的渗透图神经网络(符号)设计一个编码器,以生成四层图中所有节点的嵌入,并提出一个二次标准得分手,作为预测疾病治疗的解码器。我们对DR-Covid预测的150种潜在药物(例如地塞米松,伊维菌素)提供了详细的分析,用于不同药物类别(例如,皮质类固醇,抗病毒药,抗嗜酸盐)。在这150种药物中,目前有46种药物正在临床试验中。 DR-Covid的预测性能和对疾病的疾病的排名对疾病的排名的能力进行了评估。对于大多数疾病,DR-Covid在前15名中将实际治疗药物排名。
The 2019 novel coronavirus (SARS-CoV-2) pandemic has resulted in more than a million deaths, high morbidities, and economic distress worldwide. There is an urgent need to identify medications that would treat and prevent novel diseases like the 2019 coronavirus disease (COVID-19). Drug repurposing is a promising strategy to discover new medical indications of the existing approved drugs due to several advantages in terms of the costs, safety factors, and quick results compared to new drug design and discovery. In this work, we explore computational data-driven methods for drug repurposing and propose a dedicated graph neural network (GNN) based drug repurposing model, called Dr-COVID. Although we analyze the predicted drugs in detail for COVID-19, the model is generic and can be used for any novel diseases. We construct a four-layered heterogeneous graph to model the complex interactions between drugs, diseases, genes, and anatomies. We pose drug repurposing as a link prediction problem. Specifically, we design an encoder based on the scalable inceptive graph neural network (SIGN) to generate embeddings for all the nodes in the four-layered graph and propose a quadratic norm scorer as a decoder to predict treatment for a disease. We provide a detailed analysis of the 150 potential drugs (such as Dexamethasone, Ivermectin) predicted by Dr-COVID for COVID-19 from different pharmacological classes (e.g., corticosteroids, antivirals, antiparasitic). Out of these 150 drugs, 46 drugs are currently in clinical trials. Dr-COVID is evaluated in terms of its prediction performance and its ability to rank the known treatment drugs for diseases as high as possible. For a majority of the diseases, Dr-COVID ranks the actual treatment drug in the top 15.