摘要
目的通过生物信息学方法确定扩张性心肌病(DCM)特征基因及免疫细胞浸润。方法在两个DCM基因表达数据集上鉴定差异表达基因(DEG)并进行基因本体论(GO)、疾病本体论(DO)和基因集富集分析(GSEA)功能富集以获得潜在途径。两种机器学习算法,包括支持向量机递归特征消除(SVM-RFE)以及最小绝对收缩和选择算子(LASSO)用于确定DCM特征基因。最后运用细胞类型分析工具CIBERSORT进行免疫细胞浸润分析。结果共鉴定出51个DEG,其中机器学习算法识别硫氧还蛋白相互作用蛋白(TXNIP)、晶状体蛋白Mu(CRYM)、类热休克蛋白70蛋白A1(HSPA1L)、真核翻译延伸因子1A1(EEF1A1)为特征基因。富集分析集中在心脏过程、线粒体和细胞器的外膜、泛素样蛋白连接酶、自然杀伤细胞介导的细胞毒性,1型辅助T(Th1)细胞和Th2细胞分化,T细胞受体信号转导途径和Th17细胞分化方面。免疫细胞浸润发现幼稚B细胞,中性粒细胞和γT细胞可能参与DCM的发病过程。此外,中性粒细胞、Th细胞和M1巨噬细胞与4个特征基因高度相关。结论机器学习识别的4个特征基因TXNIP、CRYM、HSPA1L和EEF1A1可能与DCM密切相关。同时,免疫细胞浸润分析可以更好地揭示DCM的病理生理过程。
Objective To identify the characteristic genes and immune infiltration in dilated cardiomyopathy(DCM)by bioinformatic analysis.Methods We identified differentially expressed genes(DEG)on two DCM gene expression data sets,and performed gene ontology(GO),disease ontology(DO),and gene set enrichment analysis(GSEA)functional enrichment to obtain potential pathways.Two machine learning algorithms including support vector machine recursive feature elimination(SVM-RFE)algorithm and Least Absolute Shrinkage and Selection Operator(LASSO)algorithm were used to determine diagnostic markers.Finally,we used the cell type analysis tool CIBERSORT for immune cell infiltration analysis.Results A total of 51 DEGs were finally identified.Thioredoxin interacting protein(TXNIP),crystallin Mu(CRYM),heat shock 70kDa protein 1-like(HSPA1L),and eukaryotic elongation factor 1A-1(EEF1A1)were considered candidate diagnostic markers.Enrichment analysis focused on features including cardiac processes,outer membranes of mitochondria and organelles,ubiquitin-like protein ligase,natural killer cell-mediated cytotoxicity,Th1,and Th2 cell differentiation,T cell receptor signaling pathways,and Th17 cell differentiation.Immune cell infiltration found naive B cells,neutrophils,andγT cells may be involved in the pathogenesis of DCM.Besides,neutrophils,T follicular helper cells,and M1 macrophages were highly correlated with four characteristic genes.Conclusion The four characteristic genes identified by machine learning,TXNIP,CRYM,HSPA1L,and EEF1A1,show potentially close relation to DCM.At the same time,immune cell infiltration analysis can better showcase the pathophysiological process of DCM.
作者
姜晨阳
钟国强
JIANG Chenyang;ZHONG Guoqiang(Department of Cardiovascular Medicine,the First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China)
出处
《细胞与分子免疫学杂志》
CAS
CSCD
北大核心
2023年第1期26-33,共8页
Chinese Journal of Cellular and Molecular Immunology
基金
国家自然科学基金(82060068)
