转录组与单细胞相结合,探索骨关节炎中与缺氧相关的生物标记物

IF 2.8 3区 医学 Q2 BIOCHEMICAL RESEARCH METHODS Journal of Chromatography B Pub Date : 2024-08-15 DOI:10.1016/j.jchromb.2024.124274
Xingyu Liu , Guangdi Li , Riguang Liu , Lanqing Yang , Long Li , Ashutosh Goswami , Keqi Deng , Lianghong Dong , Hao Shi , Xiaoyong He
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引用次数: 0

摘要

骨关节炎(OA)是全球老年人中普遍存在的一种退化性疾病。研究表明,缺氧可促进软骨细胞凋亡和自噬,从而导致 OA。因此,筛选 OA 中与缺氧相关的生物标志物至关重要。我们引入转录组数据,在 GSE114007 和 GSE57218(OA 样本与对照样本)中筛选出差异表达基因(DEGs)。我们对关键注释细胞进行了差异表达分析,以获得单细胞水平的差异表达标记基因(GSE169454)。通过文氏图来识别与 OA 相关的缺氧相关差异表达基因(HR-DEGs)。此外,通过应用最小绝对收缩和选择算子(LASSO)回归和随机森林(RF)算法获得特征基因。接收者操作特征(ROC)和表达水平分析被用来识别OA中与缺氧相关的生物标记物。我们根据缺氧相关生物标志物进一步进行了免疫浸润和基因组富集分析(GSEA)。最后,我们分析了生物标志物在单细胞水平的表达。我们发现了 2351 个与 OA 相关的 DEGs。在单细胞水平上,我们获得了 242 个差异表达的标记基因。12个HR-DEG被保留在维恩图中。随后,我们发现了三个与缺氧相关的生物标志物(ADM、DDIT3 和 MAFF)。此外,我们还发现了 15 种明显不同的免疫细胞。最后,我们发现与对照组相比,OA 组 ECs 中 ADM、DDIT3 和 MAFF 的表达较低。总之,我们获得了与 OA 相关的三种缺氧相关生物标志物(ADM、DDIT3 和 MAFF),为解决 OA 问题奠定了理论基础。
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Transcriptome combined with single cell to explore hypoxia-related biomarkers in osteoarthritis

Osteoarthritis (OA) is a prevalent degenerative condition among the elderly on a global scale. Research has demonstrated that hypoxia can promote chondrocyte apoptosis and autophagy leading to OA. Hence, it was vital to screen the hypoxia related biomarkers in OA. We introduced transcriptome data to screen out differentially expressed genes (DEGs) in GSE114007 and GSE57218 (OA samples vs control samples). We performed differential expression analysis in key annotated cell to obtain differentially expressed marker genes at the single-cell level (GSE169454). Venn diagram was executed to identify hypoxia related differentially expressed genes (HR-DEGs) associated with OA. Further, feature genes were obtained through the application of least absolute shrinkage and selection operator (LASSO) regression and the Random Forest (RF) algorithm. Receiver operating characteristic (ROC) and expression level analysis were used to identify hypoxia related biomarkers in OA. We further performed immune infiltration and gene set enrichment analysis (GSEA) based on hypoxia related biomarkers. Finally, we analyzed the expression of biomarkers in single-cell level. We identified 2351 DEGs associated with OA. At the single-cell level, 242 differentially expressed marker genes were obtained. 12 HR-DEGs were retained venn diagram. Subsequently, three hypoxia related biomarkers (ADM, DDIT3 and MAFF) were identified. Moreover, we got 15 significantly different immune cells. Finally, we found a lower expression of ADM, DDIT3 and MAFF in OA group compared to the control group in ECs. Overall, we obtained three hypoxia related biomarkers (ADM, DDIT3 and MAFF) associated with OA, which established a theoretical basis for addressing OA.

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来源期刊
Journal of Chromatography B
Journal of Chromatography B 医学-分析化学
CiteScore
5.60
自引率
3.30%
发文量
306
审稿时长
44 days
期刊介绍: The Journal of Chromatography B publishes papers on developments in separation science relevant to biology and biomedical research including both fundamental advances and applications. Analytical techniques which may be considered include the various facets of chromatography, electrophoresis and related methods, affinity and immunoaffinity-based methodologies, hyphenated and other multi-dimensional techniques, and microanalytical approaches. The journal also considers articles reporting developments in sample preparation, detection techniques including mass spectrometry, and data handling and analysis. Developments related to preparative separations for the isolation and purification of components of biological systems may be published, including chromatographic and electrophoretic methods, affinity separations, field flow fractionation and other preparative approaches. Applications to the analysis of biological systems and samples will be considered when the analytical science contains a significant element of novelty, e.g. a new approach to the separation of a compound, novel combination of analytical techniques, or significantly improved analytical performance.
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