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利用基因表达综合数据库探讨RNA N6-甲基腺嘌呤调节剂在儿童哮喘诊断及亚型分类中的意义

Significance of RNA N6-Methyladenosine Regulators in the Diagnosis and Subtype Classification of Childhood Asthma Using the Gene Expression Omnibus Database.

作者信息

Dai Bing, Sun Feifei, Cai Xuxu, Li Chunlu, Liu Henan, Shang Yunxiao

机构信息

Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, China.

Department of Ultrasound, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Front Genet. 2021 Mar 2;12:634162. doi: 10.3389/fgene.2021.634162. eCollection 2021.

Abstract

RNA N6-methyladenosine (m6A) regulators play important roles in a variety of biological functions. Nonetheless, the roles of m6A regulators in childhood asthma remain unknown. In this study, 11 significant m6A regulators were selected using difference analysis between non-asthmatic and asthmatic patients from the Gene Expression Omnibus GSE40888 dataset. The random forest model was used to screen five candidate m6A regulators (fragile X mental retardation 1, KIAA1429, Wilm's tumor 1-associated protein, YTH domain-containing 2, and zinc finger CCCH domain-containing protein 13) to predict the risk of childhood asthma. A nomogram model was established based on the five candidate m6A regulators. Decision curve analysis indicated that patients could benefit from the nomogram model. The consensus clustering method was performed to differentiate children with asthma into two m6A patterns (clusterA and clusterB) based on the selected significant m6A regulators. Principal component analysis algorithms were constructed to calculate the m6A score for each sample to quantify the m6A patterns. The patients in clusterB had higher m6A scores than those in clusterA. Furthermore, we found that the patients in clusterA were linked to helper T cell type 1 (Th1)-dominant immunity while those in clusterB were linked to Th2-dominant immunity. In summary, m6A regulators play nonnegligible roles in the occurrence of childhood asthma. Our investigation of m6A patterns may be able to guide future immunotherapy strategies for childhood asthma.

摘要

RNA N6-甲基腺嘌呤(m6A)调节剂在多种生物学功能中发挥重要作用。尽管如此,m6A调节剂在儿童哮喘中的作用仍不清楚。在本研究中,通过对基因表达综合数据库GSE40888数据集中非哮喘患者和哮喘患者进行差异分析,筛选出11个重要的m6A调节剂。使用随机森林模型筛选出5个候选m6A调节剂(脆性X智力低下蛋白1、KIAA1429、威尔姆斯瘤1相关蛋白、含YTH结构域蛋白2和含锌指CCCH结构域蛋白13)来预测儿童哮喘风险。基于这5个候选m6A调节剂建立了列线图模型。决策曲线分析表明患者可从列线图模型中获益。采用一致性聚类方法,根据选定的重要m6A调节剂将哮喘儿童分为两种m6A模式(簇A和簇B)。构建主成分分析算法来计算每个样本的m6A评分,以量化m6A模式。簇B中的患者m6A评分高于簇A中的患者。此外,我们发现簇A中的患者与辅助性T细胞1型(Th1)主导的免疫相关,而簇B中的患者与Th2主导的免疫相关。总之,m6A调节剂在儿童哮喘的发生中起不可忽视的作用。我们对m6A模式的研究可能能够指导未来儿童哮喘的免疫治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bb26/7982807/5053ceedc84b/fgene-12-634162-g001.jpg

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