论文标题
网络增强驱动的药物对COVID-19通过利用疾病与药物的关联
Network reinforcement driven drug repurposing for COVID-19 by exploiting disease-gene-drug associations
论文作者
论文摘要
目前,COVID-19患者数量已显着增加。因此,迫切需要开发与-19的治疗方法。药物重新利用是重复使用已经批准的新医疗状况的药物的过程,可以是快速而广泛地解决此问题的好方法。许多使用其他疾病治疗的COVID-19患者进行的许多临床试验已经存在或将在不久的将来在临床部位进行。此外,合并症,例如糖尿病,肥胖症,肝硬化,肾脏疾病,高血压和哮喘的患者的患者患严重疾病的风险较高。因此,合并症疾病与COVID-19的关系可能有助于找到可再利用的药物。为了减少发现COVID-19的治疗方法的试验和错误,我们建议建立一个基于网络的药物重新利用框架,以优先考虑可重新利用的药物。首先,我们利用COVID-19的知识来构建代表与疾病,基因和药物的成分相互作用的疾病基因网络(DGDR-NET)。 DGDR-NET由592种疾病,26,681种人体基因和2,173种药物以及18种常见合并症的医学信息组成。 DGDR-NET建议通过网络增强驱动的评分算法为COVID-19的候选候选药物。评分算法通过利用基于图形的半监督学习来确定建议的优先级。从预测的分数中,我们建议将30种药物,包括地塞米松,白藜芦醇,甲氨蝶呤,吲哚美辛,槲皮素等,作为Covid-19的可重新提示药物,并通过临床试验的药物进行了证实。通过数据驱动的计算方法列表可以帮助减少发现Covid-19的治疗方法的试验。
Currently, the number of patients with COVID-19 has significantly increased. Thus, there is an urgent need for developing treatments for COVID-19. Drug repurposing, which is the process of reusing already-approved drugs for new medical conditions, can be a good way to solve this problem quickly and broadly. Many clinical trials for COVID-19 patients using treatments for other diseases have already been in place or will be performed at clinical sites in the near future. Additionally, patients with comorbidities such as diabetes mellitus, obesity, liver cirrhosis, kidney diseases, hypertension, and asthma are at higher risk for severe illness from COVID-19. Thus, the relationship of comorbidity disease with COVID-19 may help to find repurposable drugs. To reduce trial and error in finding treatments for COVID-19, we propose building a network-based drug repurposing framework to prioritize repurposable drugs. First, we utilized knowledge of COVID-19 to construct a disease-gene-drug network (DGDr-Net) representing a COVID-19-centric interactome with components for diseases, genes, and drugs. DGDr-Net consisted of 592 diseases, 26,681 human genes and 2,173 drugs, and medical information for 18 common comorbidities. The DGDr-Net recommended candidate repurposable drugs for COVID-19 through network reinforcement driven scoring algorithms. The scoring algorithms determined the priority of recommendations by utilizing graph-based semi-supervised learning. From the predicted scores, we recommended 30 drugs, including dexamethasone, resveratrol, methotrexate, indomethacin, quercetin, etc., as repurposable drugs for COVID-19, and the results were verified with drugs that have been under clinical trials. The list of drugs via a data-driven computational approach could help reduce trial-and-error in finding treatment for COVID-19.