Ran Ming-Yu, Yuan Zhang, Fan Chui-Ting, Ke Zhou, Wang Xin-Xing, Sun Jia-Yuan, Su Dong-Ju
Department of College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
Department of Respiratory, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Front Cell Dev Biol. 2021 Dec 14;9:744932. doi: 10.3389/fcell.2021.744932. eCollection 2021.
Asthma is a complex heterogeneous respiratory disorder. In recent years nubbly regions of the role of genetic variants and transcriptome including mRNAs, microRNAs, and long non-coding RNAs in the pathogenesis of asthma have been separately excavated and reported. However, how to systematically integrate and decode this scattered information remains unclear. Further exploration would improve understanding of the internal communication of asthma. To excavate new insights into the pathogenesis of asthma, we ascertained three asthma characteristics according to reviews, airway inflammation, airway hyperresponsiveness, and airway remodeling. We manually created a contemporary catalog of corresponding risk transcriptome, including mRNAs, miRNAs, and lncRNAs. MIMP is a multiplex-heterogeneous networks-based approach, measuring the relevance of disease characteristics to the pathway by examining the similarity between the determined vectors of risk transcriptome and pathways in the same low-dimensional vector space. It was developed to enable a more concentrated and in-depth exploration of potential pathways. We integrated experimentally validated competing endogenous RNA regulatory information and the SNPs with significant pathways into the ceRNA-mediated SNP switching pathway network (CSSPN) to analyze ceRNA regulation of pathways and the role of SNP in these dysfunctions. We discovered 11 crucial ceRNA regulations concerning asthma disease feature pathway and propose a potential mechanism of ceRNA regulatory SNP → gene → pathway → disease feature effecting asthma pathogenesis, especially for MALAT1 (rs765499057/rs764699354/rs189435941) → hsa-miR-155 → IL13 (rs201185816/rs1000978586/rs202101165) → Interleukin-4 and Interleukin-13 signaling → inflammation/airway remodeling and MALAT1 (rs765499057/rs764699354/rs189435941) → hsa-miR-155 → IL17RB (rs948046241) → Interleukin-17 signaling (airway remodeling)/Cytokine-cytokine receptor interaction (inflammation). This study showed a systematic and propagable workflow for capturing the potential SNP "switch" of asthma through text and database mining and provides further information on the pathogenesis of asthma.
哮喘是一种复杂的异质性呼吸系统疾病。近年来，基因变异和转录组（包括信使核糖核酸、微小核糖核酸和长链非编码核糖核酸）在哮喘发病机制中的作用的多个方面已被分别挖掘和报道。然而，如何系统地整合和解码这些分散的信息仍不清楚。进一步的探索将有助于增进对哮喘内部关联的理解。为了挖掘哮喘发病机制的新见解，我们根据综述确定了哮喘的三个特征：气道炎症、气道高反应性和气道重塑。我们手动创建了一个相应风险转录组的当代目录，包括信使核糖核酸、微小核糖核酸和长链非编码核糖核酸。MIMP是一种基于多重异质网络的方法，通过在相同的低维向量空间中检查风险转录组的确定向量与通路之间的相似性，来衡量疾病特征与通路的相关性。它的开发是为了能够更集中、更深入地探索潜在通路。我们将经过实验验证的竞争性内源性RNA调控信息和具有显著通路的单核苷酸多态性整合到ceRNA介导的SNP转换通路网络（CSSPN）中，以分析ceRNA对通路的调控以及SNP在这些功能障碍中的作用。我们发现了11条与哮喘疾病特征通路相关的关键ceRNA调控，并提出了一种ceRNA调控SNP→基因→通路→疾病特征影响哮喘发病机制的潜在机制，特别是对于MALAT1（rs765499057/rs764699354/rs189435941）→hsa-miR-155→IL13（rs201185816/rs1000978586/rs202101165）→白细胞介素-4和白细胞介素-13信号通路→炎症/气道重塑以及MALAT1（rs765499057/rs764699354/rs189435941）→hsa-miR-155→IL17RB（rs948046241）→白细胞介素-17信号通路（气道重塑）/细胞因子-细胞因子受体相互作用（炎症）。这项研究展示了一种通过文本和数据库挖掘来捕捉哮喘潜在SNP“开关”的系统且可推广的工作流程，并为哮喘的发病机制提供了更多信息。
