Significance of RNA N6-Methyladenosine Regulators in the Diagnosis and Subtype Classification of Childhood Asthma Using the Gene Expression Omnibus Database.
Significance of RNA N6-Methyladenosine Regulators in the Diagnosis and Subtype Classification of Childhood Asthma Using the Gene Expression Omnibus Database.
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RNA N6-甲基腺苷调节剂在使用基因表达综合数据库诊断和儿童哮喘亚型分类中的意义
DOI：
10.3389/fgene.2021.634162
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发表时间：
2021
影响因子：
3.7
通讯作者：
Shang Y
中科院分区：
文献类型：
--
作者：
Dai B;Sun F;Cai X;Li C;Liu H;Shang Y
RNA N6-甲基腺苷（m6 A）调节剂在多种生物学功能中发挥重要作用。尽管如此，m6 A调节剂在儿童哮喘中的作用仍然未知。在这项研究中，使用来自基因表达Omnibus GSE 40888数据集的非哮喘患者和哮喘患者之间的差异分析，选择了11种显著的m6 A调节剂。随机森林模型用于筛选5个候选m6 A调节因子（脆性X智力低下1、KIAA 1429、Wilm's肿瘤1相关蛋白、含YTH结构域2和含锌指CCCH结构域蛋白13）以预测儿童哮喘的风险。基于5个候选m6 A调节子建立诺模图模型。决策曲线分析表明患者可以从诺模图模型中受益。一致性聚类方法进行区分儿童哮喘分为两个m6 A模式（clusterA和clusterB）的基础上选择显着的m6 A调节。构建主成分分析算法以计算每个样品的m6 A分数，从而量化m6 A模式。B群患者的m6 A评分高于A群患者。此外，我们发现，在clusterA中的患者与辅助性T细胞1型（Th 1）-显性免疫，而在clusterB中的患者与Th 2-显性免疫。总之，m6 A调节剂在儿童哮喘的发生中起着不可忽视的作用。我们对m6 A模式的研究可能能够指导未来儿童哮喘的免疫治疗策略。
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.