Khoo Li Ying, Dhillon Sarinder Kaur
Data Science and Bioinformatics Laboratory, Institute of Biological Sciences, Faculty of Science, Universiti of Malaya, Lembah Pantai, 50603, Kuala Lumpur, Malaysia.
Sci Rep. 2025 Jun 4;15(1):19644. doi: 10.1038/s41598-025-03640-1.
Prior coronavirus disease 2019 (COVID-19) transcriptomic studies using diverse methods for differential gene expression (DGE) profiling of specific samples yielded inconsistent results. To validate the shared molecular patterns of COVID-19 across cell, tissue, and systemic levels, we conducted a systematic rank combination meta-analysis of differentially expressed gene (DEG) profiles sourced from various sample types using a standardised bioinformatics pipeline consisting of DESeq2, RankProd, and weighted gene correlation network analysis (WGCNA). Consistently upregulated ISGs (including key hub gene IFIT2), compared with interleukins were identified in swab samples, reflecting dominant innate immune responses at the viral entry point. Blood samples revealed diverse gene functions in immune and neurological regulation, highlighting the complex interplay of systemic regulation. Significant enrichment of immunoglobulin-related and extracellular matrix genes indicates their role in the host adaptive immunity and long-term host responses in tissue samples. Novel key hub genes in tissue samples, GPD1 and CYP4A11 related to metabolic dysregulation were identified, potentially contributing to the severity of the disease. These findings portray the molecular basis of COVID-19 progression from localised innate responses to systemic effects and finally tissue-specific adaptive immunity and remodelling, providing insights that may inform diagnostic and therapeutic development.
先前针对2019冠状病毒病（COVID-19）的转录组学研究使用了多种方法对特定样本进行差异基因表达（DGE）分析，结果并不一致。为了验证COVID-19在细胞、组织和全身水平上的共同分子模式，我们使用由DESeq2、RankProd和加权基因共表达网络分析（WGCNA）组成的标准化生物信息学流程，对来自各种样本类型的差异表达基因（DEG）谱进行了系统的秩组合荟萃分析。与白细胞介素相比，拭子样本中一致上调的ISG（包括关键枢纽基因IFIT2）被鉴定出来，反映了病毒进入点处占主导地位的固有免疫反应。血液样本揭示了免疫和神经调节中多种基因功能，突出了全身调节的复杂相互作用。免疫球蛋白相关基因和细胞外基质基因的显著富集表明它们在宿主适应性免疫和组织样本中宿主长期反应中的作用。在组织样本中鉴定出与代谢失调相关的新关键枢纽基因GPD1和CYP4A11，可能导致疾病严重程度增加。这些发现描绘了COVID-19从局部固有反应发展到全身效应，最终发展为组织特异性适应性免疫和重塑的分子基础，为诊断和治疗发展提供了参考见解。
