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pmid:36864526
Landscape analysis of m6A modification regulators related biological functions and immune characteristics in myasthenia gravis.
Shuang Li · Hui Liu · Zhe Ruan · Rongjing Guo · Chao Sun · Yonglan Tang · Xiaoxi Huang · Ting Gao · Sijia Hao · Huanhuan Li · Na Song · Yue Su · Fan Ning · Zhuyi Li · Ting Chang
Journal of translational medicine · 2023 doi:10.1186/s12967-023-03947-5
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Experiment
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Complete file
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However, the implication of m6A modification in myasthenia gravis (MG) remains largely unknown. Thus, we aimed to systematically explore the potential functions and related immune characteristics of m6A regulators in MG.\nMETHODS: The GSE85452 dataset with MG and healthy samples was downloaded from Gene Expression Omnibus (GEO) database. m6A modification regulators were manually curated. The targets of m6A regulators were obtained from m6A2Target database. The differential expressed m6A regulators in GSE85452 dataset were identified by \"limma\" package and were validated by RT-PCR. Function enrichment analysis of dysregulated m6A regulators was performed using \"clusterProfiler\" package. Correlation analysis was applied for analyzing the relationships between m6A regulators and immune characteristics. Unsupervised clustering analysis was used to identify distinct m6A modification subtypes. The differences between subtypes were analyzed, including the expression level of all genes and the enrichment degree of immune characteristics. Weighted gene co-expression network analysis (WGCNA) was conducted to obtain modules associated with m6A modification subtypes.\nRESULTS: We found that CBLL1, RBM15 and YTHDF1 were upregulated in MG samples of GSE85452 dataset, and the results were verified by RT-PCR in blood samples from19 MG patients and 19 controls. The targeted genes common modified by CBLL1, RBM15, and YTHDF1 were mainly enriched in histone modification and Wnt signaling pathway. Correlation analysis showed that three dysregulated m6A regulators were closely associated with immune characteristics. Among them, RBM15 possessed the strongest correlation with immune characteristics, including CD56dim natural killer cell (r = 0.77, P = 0.0023), T follicular helper cell (r = - 0.86, P = 0.0002), Interferon Receptor (r = 0.78, P = 0.0017), and HLA-DOA (r = 0.64, P = 0.0200). Further two distinct m6A modification patterns mediated by three dysregulated m6A regulators was identified. Bioinformatics analysis found that there were 3029 differentially expressed genes and different immune characteristics between two m6A modification patterns. Finally, WGCNA analysis obtained a total of 12 modules and yellow module was the most positively correlated to subtype-2.\nCONCLUSION: Our findings suggested that m6A RNA modification had an important effect on immunity molecular mechanism of MG and provided a new perspective into understanding the pathogenesis of MG.", "claims": [{"id": "claim-method", "statement": "The differentially expression genes (DEGs) between MG samples and healthy samples were determined using “Empirical Bayes method” in the R package “limma”.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36864526", "locator": "sections[4] \"Differentially expression analysis and screening MG-related m6A regulators\" paragraph 2", "quote": "The differentially expression genes (DEGs) between MG samples and healthy samples were determined using “Empirical Bayes method” in the R package “limma”."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Although the study is based on mined data (GEO), the analysis and plots are original. The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36864526", "locator": "sections[27] \"Availability of data and materials\" paragraph 2", "quote": "Although the study is based on mined data (GEO), the analysis and plots are original. The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "CBLL1, RBM15 and YTHDF1 were upregulated in MG samples of GSE85452 dataset, and the results were verified by RT-PCR in blood samples from19 MG patients and 19 controls.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36864526", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We found that CBLL1, RBM15 and YTHDF1 were upregulated in MG samples of GSE85452 dataset, and the results were verified by RT-PCR in blood samples from19 MG patients and 19 controls."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "CBLL1, RBM15 and YTHDF1 were upregulated in MG samples of GSE85452 dataset, and the results were verified by RT-PCR in blood samples from19 MG patients and 19 controls.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:36864526"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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