Regulation of m7G methylation in long COVID: Expression profiles and early predictive value of key genes, 2025, Bai and Li

[SNT Gatchaman]

Regulation of m7G methylation in long COVID: Expression profiles and early predictive value of key genes
Bai, Wenmei; Li, Fengsen

Long COVID (LC) poses ongoing public health challenges due to its persistent symptoms following severe acute respiratory syndrome coronavirus 2 infection. Early identification of at-risk individuals remains difficult, and molecular biomarkers are urgently needed. This study aimed to explore the role of N7-methylguanosine (m7G) methylation-related regulatory genes in LC pathogenesis and to develop a predictive model for early detection.

Gene expression profiles of LC patients were obtained from the GEO database (GSE224615), and differentially expressed genes (DEGs) were identified. These DEGs were intersected with m7G regulatory genes to identify LC-specific candidates. A protein–protein interaction network was constructed to identify hub genes, and enrichment analyses including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis were performed to investigate the biological relevance of the identified genes. Immune cell infiltration analyses were conducted to explore the immunological features associated with candidate genes.

Findings were validated using an external dataset (GSE217948). A clinical prediction model was constructed using Least absolute shrinkage and selection operator regression followed by logistic regression, and evaluated via receiver operating characteristic curve, calibration, and decision curve analysis.

A total of 65 DEGs were identified in LC patients, comprising 44 up-regulated and 21 down-regulated genes. Thirty genes overlapped with the m7G regulatory gene set. Functional enrichment revealed significant involvement in pathways such as FceRI-mediated NF-κB activation and platelet aggregation. Correlation analysis showed that several m7G-related genes were associated with altered immune cell infiltration patterns. The external dataset confirmed the reproducibility of gene expression trends. Seven core genes were ultimately selected to build the predictive model, which demonstrated robust performance in distinguishing LC patients from controls.

This study highlights the importance of m7G methylation in LC pathogenesis and uncovers novel immune-related mechanisms underlying its persistence. The predictive model based on m7G-related markers provides a promising tool for early LC identification and may inform future diagnostic and therapeutic strategies.

Web | Medicine | Open Access

 

[SNT Gatchaman]

N7-methylguanosine (m7G) constitutes a ubiquitous RNA modification, with its initial documentation dating back to the 1970s.

The m7G modification exerts a profound impact on RNA processing, metabolism, and functional attributes. […] contemporary research has unveiled that m7G modifications are not confined solely to mRNA, they are also encountered at internal locations within diverse RNA categories, including transfer RNA, ribosomal RNA, and mRNA. Hence, it is a plausible hypothesis that individuals suffering from LC may manifest anomalies in the m7G methylation process.

we accessed data pertaining to “LC” from the Gene Expression Omnibus database (GEO) available at http://www.ncbi.nlm.nih.gov/geo/. Subsequently, we identified a pertinent microarray dataset denoted as GSE224615. GSE224615 consisted of a total of 36 samples, encompassing 13 non-long COVID (non-LC) samples and 23 LC samples. To further substantiate our findings, we incorporated an additional dataset, GSE217948, which encompassed a more extensive collection of samples. This dataset comprised 334 individuals who tested positive for COVID-19 infection, along with 62 control samples.

We conducted an intersection analysis between the differentially expressed genes observed in LC patients and genes associated with m7G methylation regulation.

This analysis resulted in the identification of 30 genes that were common to both datasets

To elucidate the interactions among differentially expressed key regulatory factors of m7G methylation in patients with LC, we conducted a PPI analysis […] The outcomes unveiled the most significant GO-enriched terms, encompassing processes like blood coagulation and coagulation (biological processes), cellular components such as hemoglobin complex and endocytic vesicle lumen, and molecular functions including peroxidase activity and haptoglobin binding

Subsequently, it was observed that 8 genes displayed a significant upregulation in expression within the COVID group, while 5 genes exhibited downregulated expression

Among the 13 pivotal genes, we discerned 7 genes utilizing the least absolute shrinkage and selection operator regression model. […] The genes include adrenergic receptor alpha 2A, carbonic anhydrase 1, chromodomain helicase DNA binding protein 5, claudin 9, integrin alpha D, SERPINE1, tumor necrosis factor receptor superfamily member 17

 

[SNT Gatchaman]

The genes include adrenergic receptor alpha 2A, carbonic anhydrase 1, chromodomain helicase DNA binding protein 5, claudin 9, integrin alpha D, SERPINE1, tumor necrosis factor receptor superfamily member 17

Carbonic anhydrase 1 is CA1.

Noting that CA10 was a significant gene in DecodeME, although that may not be relevant as CA10 is acatalytic and likely has a completely different function, in specific tissues.