基于DeepGENE的CAV和CAVIN家族基因在急性肺损伤中的作用机制

IF 3.8 4区医学 Q2 GENETICS & HEREDITY

Current gene therapy Pub Date : 2023-01-01 DOI:10.2174/1566523222666220829140649

Changsheng Li, Hexiao Tang, Zetian Yang, Zheng Tang, Nitao Cheng, Jingyu Huang, Xuefeng Zhou

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引用次数: 0

摘要

背景:急性肺损伤(ALI)致死率高达40% ~ 60%。虽然脓毒症、创伤、肺炎、烧伤、输血、体外循环、胰腺炎等多种因素均可诱发ALI，但具有这些危险因素的患者最终会发展为ALI。ALI的发生率不高，ALI患者的转归也各不相同，提示其与个体间的遗传差异有关。在之前的研究中，我们发现了cavin-2在肺功能中的多种功能。此外，许多其他研究表明，CAV1是肺损伤的关键调节因子。由于cavin-2和CAV1之间的密切关系，我们怀疑cavin-2也与ALI有关。此外，我们对CAV家族和cavin家族基因在ALI中的作用感到好奇。方法:为了揭示CAV和CAVIN家族基因在ALI中的作用机制，我们提出了DeepGENE来预测CAV和CAVIN家族基因是否与ALI相关。该方法构建了基因相互作用网络，提取了84个组织的基因表达。我们将这些特征分为两组，并使用两个网络编码器对特征进行编码和学习。结果:与DNN、GBDT、RF和KNN相比，DeepGENE的AUC分别增加了7.89%、16.84%、20.19%和32.01%。AUPR评分分别提高8.05%、15.58%、22.56%和23.34%。DeepGENE表明，CAVIN-1、CAVIN-2、CAVIN-3和CAV2与ALI有关。结论:DeepGENE是鉴定急性肺损伤相关基因的可靠方法。多个CAV和CAVIN家族基因通过多种途径和基因功能与急性肺损伤相关基因相关。

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Mechanism of CAV and CAVIN Family Genes in Acute Lung Injury based on DeepGENE.

Background: The fatality rate of acute lung injury (ALI) is as high as 40% to 60%. Although various factors, such as sepsis, trauma, pneumonia, burns, blood transfusion, cardiopulmonary bypass, and pancreatitis, can induce ALI, patients with these risk factors will eventually develop ALI. The rate of developing ALI is not high, and the outcomes of ALI patients vary, indicating that it is related to genetic differences between individuals. In a previous study, we found multiple functions of cavin-2 in lung function. In addition, many other studies have revealed that CAV1 is a critical regulator of lung injury. Due to the strong relationship between cavin-2 and CAV1, we suspect that cavin-2 is also associated with ALI. Furthermore, we are curious about the role of the CAV family and cavin family genes in ALI.

Methods: To reveal the mechanism of CAV and CAVIN family genes in ALI, we propose DeepGENE to predict whether CAV and CAVIN family genes are associated with ALI. This method constructs a gene interaction network and extracts gene expression in 84 tissues. We divided these features into two groups and used two network encoders to encode and learn the features.

Results: Compared with DNN, GBDT, RF and KNN, the AUC of DeepGENE increased by 7.89%, 16.84%, 20.19% and 32.01%, respectively. The AUPR scores increased by 8.05%, 15.58%, 22.56% and 23.34%. DeepGENE shows that CAVIN-1, CAVIN-2, CAVIN-3 and CAV2 are related to ALI.

Conclusion: DeepGENE is a reliable method for identifying acute lung injury-related genes. Multiple CAV and CAVIN family genes are associated with acute lung injury-related genes through multiple pathways and gene functions.

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来源期刊

Current gene therapy 医学-遗传学

CiteScore

6.70

自引率

2.80%

发文量

期刊介绍： Current Gene Therapy is a bi-monthly peer-reviewed journal aimed at academic and industrial scientists with an interest in major topics concerning basic research and clinical applications of gene and cell therapy of diseases. Cell therapy manuscripts can also include application in diseases when cells have been genetically modified. Current Gene Therapy publishes full-length/mini reviews and original research on the latest developments in gene transfer and gene expression analysis, vector development, cellular genetic engineering, animal models and human clinical applications of gene and cell therapy for the treatment of diseases. Current Gene Therapy publishes reviews and original research containing experimental data on gene and cell therapy. The journal also includes manuscripts on technological advances, ethical and regulatory considerations of gene and cell therapy. Reviews should provide the reader with a comprehensive assessment of any area of experimental biology applied to molecular medicine that is not only of significance within a particular field of gene therapy and cell therapy but also of interest to investigators in other fields. Authors are encouraged to provide their own assessment and vision for future advances. Reviews are also welcome on late breaking discoveries on which substantial literature has not yet been amassed. Such reviews provide a forum for sharply focused topics of recent experimental investigations in gene therapy primarily to make these results accessible to both clinical and basic researchers. Manuscripts containing experimental data should be original data, not previously published.