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pmid:39313785
Innovative biomarkers TCN2 and LY6E can significantly inhibit respiratory syncytial virus infection.
Bochun Cao · Menglu Li · Xiaoping Li · Xianyan Ji · Lin Wan · Yingying Jiang · Lu Zhou · Fang Gong · Xiangjie Chen
Journal of translational medicine · 2024 doi:10.1186/s12967-024-05677-8
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Complete file
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Despite notable progress in the diagnosis and management of pediatric RSV infection, the current biomarkers for early-stage detection remain insufficient to meet clinical needs. Therefore, the development of more effective biomarkers for early-stage pediatric respiratory syncytial virus infection (EPR) is imperative.\nMETHODS: The datasets used in this study were derived from the Gene Expression Omnibus (GEO) database. We used GSE188427 dataset as the training set to screen for biomarkers. Biomarkers of EPR were screened by Weighted Gene Co-expression Network Analysis (WGCNA), three machine-learning algorithms (LASSO regression, Random Forest, XGBoost), and other comprehensive bioinformatics analysis techniques. To evaluate the diagnostic value of these biomarkers, multiple external and internal datasets were employed as validation sets. Next, an examination was performed to investigate the relationship between the screened biomarkers and the infiltration of immune cells. Furthermore, an investigation was carried out to identify potential small molecule compounds that interact with selected diagnostic markers. Finally, we confirmed that the expression levels of the selected biomarkers exhibited a significant increase following RSV infection, and they were further identified as having antiviral properties.\nRESULTS: The study found that lymphocyte antigen 6E (LY6E) and Transcobalamin-2 (TCN2) are two biomarkers with diagnostic significance in EPR. Analysis of immune cell infiltration showed that they were associated with activation of multiple immune cells. Furthermore, our analysis demonstrated that small molecules, 3'-azido-3'-deoxythymine, methotrexate, and theophylline, have the potential to bind to TCN2 and exhibit antiviral properties. These compounds may serve as promising therapeutic agents for the management of pediatric RSV infections. Additionally, our data revealed an upregulation of LY6E and TCN2 expression in PBMCs from patients with RSV infection. ROC analysis indicated that LY6E and TCN2 possessed diagnostic value for RSV infection. Finally, we confirmed that LY6E and TCN2 expression increased after RSV infection and further inhibited RSV infection in A549 and BEAS-2B cell lines. Importantly, based on TCN2, our findings revealed the antiviral properties of a potentially efficacious compound, vitamin B12.\nCONCLUSION: LY6E and TCN2 are potential peripheral blood diagnostic biomarkers for pediatric RSV infection. LY6E and TCN2 inhibit RSV infection, indicating that LY6E and TCN2 are potential therapeutic target for RSV infection.", "claims": [{"id": "claim-data-access", "statement": "All data are available and the correspondent can be contacted if requested.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39313785", "locator": "sections[35] \"notes\" paragraph 1", "quote": "All data are available and the correspondent can be contacted if requested."}], "state": "complete"}, {"id": "claim-target-result", "statement": "LY6E and TCN2 were identified as potential peripheral blood diagnostic biomarkers for pediatric RSV infection.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39313785", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "LY6E and TCN2 are potential peripheral blood diagnostic biomarkers for pediatric RSV infection."}, {"asset": "source:pmid:39313785", "locator": "sections[22] \"Screening and validation of diagnostic markers\" paragraph 2", "quote": "In dataset GSE188427, the area under the curve (AUC) of LY6E and TCN2 were > 0.9 (Fig. 5A); in dataset GSE80179, the AUC of LY6E and TCN2 were > 0.8 (Fig. 5B)."}, {"asset": "source:pmid:39313785", "locator": "sections[22] \"Screening and validation of diagnostic markers\" paragraph 2", "quote": "In dataset GSE105450, the AUC of LY6E and TCN2 were ≥ 0.9 (Fig. 5C); In dataset GSE77087, the AUC of LY6E and TCN2 were > 0.9 (Fig. 5D)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "LY6E and TCN2 were identified as potential peripheral blood diagnostic biomarkers for pediatric RSV infection.", "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:39313785"], "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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