论文标题

通过大规模表达曲线对COVID-19的加速药物来加速药物。

Accelerating drug repurposing for COVID-19 via modeling drug mechanism of action with large scale gene-expression profiles

论文作者

Han, Lu, Shan, G. C., Chu, B. F., Wang, H. Y., Wang, Z. J., Gao, S. Q., Zhou, W. X.

论文摘要

新颖的冠状病毒疾病(名为Covid-19)于2019年12月出现在中国,并迅速遍及世界各地。显然,在全球范围内与Covid-19作战显然是迫切的。基于表型数据识别药物使用的方法的开发可以提高药物开发的效率。但是,基于细胞图片数据识别药物应用仍然存在许多困难。这项工作报告了一种最先进的机器学习方法,可以根据lincs计划中生成的1024种药物的细胞图像特征来识别药物用途。由于图像的多维特征受非实验因素的影响,因此相似药物的特征差异很大,并且当前的样本数不足以使用深度学习和其他方法用于学习优化。结果,这项研究基于受监督的ITML算法转换药物特征。结果表明,ITML转化的特征更有利于识别药物功能。对特征转化的分析表明,不同特征在识别不同的药物功能方面起着重要作用。对于当前的Covid-19,氯喹和羟氯喹通过抑制内吞作用等实现抗病毒作用,并被分类到同一社区。在同一社区中的克罗米芬(Clomiphene)诱使埃博拉病毒的进入,表明可以通过细胞图像反映的类似的MOA。

The novel coronavirus disease, named COVID-19, emerged in China in December 2019, and has rapidly spread around the world. It is clearly urgent to fight COVID-19 at global scale. The development of methods for identifying drug uses based on phenotypic data can improve the efficiency of drug development. However, there are still many difficulties in identifying drug applications based on cell picture data. This work reported one state-of-the-art machine learning method to identify drug uses based on the cell image features of 1024 drugs generated in the LINCS program. Because the multi-dimensional features of the image are affected by non-experimental factors, the characteristics of similar drugs vary greatly, and the current sample number is not enough to use deep learning and other methods are used for learning optimization. As a consequence, this study is based on the supervised ITML algorithm to convert the characteristics of drugs. The results show that the characteristics of ITML conversion are more conducive to the recognition of drug functions. The analysis of feature conversion shows that different features play important roles in identifying different drug functions. For the current COVID-19, Chloroquine and Hydroxychloroquine achieve antiviral effects by inhibiting endocytosis, etc., and were classified to the same community. And Clomiphene in the same community inibited the entry of Ebola Virus, indicated a similar MoAs that could be reflected by cell image.

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