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在基于机器学习的方法中使用信息特征进行新冠病毒药物重新利用研究。

Using informative features in machine learning based method for COVID-19 drug repurposing.

作者信息

Aghdam Rosa, Habibi Mahnaz, Taheri Golnaz

机构信息

School of Biological Sciences, Institute for Research in Fundamental Sciences (IPM), Tehran, Iran.

Department of Mathematics, Qazvin Branch, Islamic Azad University, Qazvin, Iran.

出版信息

J Cheminform. 2021 Sep 20;13(1):70. doi: 10.1186/s13321-021-00553-9.

Abstract

Coronavirus disease 2019 (COVID-19) is caused by a novel virus named Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This virus induced a large number of deaths and millions of confirmed cases worldwide, creating a serious danger to public health. However, there are no specific therapies or drugs available for COVID-19 treatment. While new drug discovery is a long process, repurposing available drugs for COVID-19 can help recognize treatments with known clinical profiles. Computational drug repurposing methods can reduce the cost, time, and risk of drug toxicity. In this work, we build a graph as a COVID-19 related biological network. This network is related to virus targets or their associated biological processes. We select essential proteins in the constructed biological network that lead to a major disruption in the network. Our method from these essential proteins chooses 93 proteins related to COVID-19 pathology. Then, we propose multiple informative features based on drug-target and protein-protein interaction information. Through these informative features, we find five appropriate clusters of drugs that contain some candidates as potential COVID-19 treatments. To evaluate our results, we provide statistical and clinical evidence for our candidate drugs. From our proposed candidate drugs, 80% of them were studied in other studies and clinical trials.

摘要

2019冠状病毒病(COVID-19)由一种名为严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的新型病毒引起。该病毒在全球导致大量死亡和数百万确诊病例,对公众健康构成严重威胁。然而,目前尚无针对COVID-19治疗的特异性疗法或药物。虽然新药研发是一个漫长的过程,但将现有药物重新用于COVID-19治疗有助于识别具有已知临床特征的治疗方法。计算药物重新利用方法可以降低药物毒性的成本、时间和风险。在这项工作中,我们构建了一个作为与COVID-19相关的生物网络的图。该网络与病毒靶点或其相关的生物学过程有关。我们在构建的生物网络中选择导致网络重大破坏的必需蛋白质。我们从这些必需蛋白质中选择了93种与COVID-19病理学相关的蛋白质。然后,我们基于药物-靶点和蛋白质-蛋白质相互作用信息提出了多个信息特征。通过这些信息特征,我们发现了五个合适的药物簇,其中包含一些作为潜在COVID-19治疗药物的候选药物。为了评估我们的结果,我们为我们的候选药物提供了统计和临床证据。在我们提出的候选药物中,80%在其他研究和临床试验中进行过研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/67ef/8454184/58df22bead39/13321_2021_553_Fig1_HTML.jpg

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