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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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title
Innovative biomarkers TCN2 and LY6E can significantly inhibit respiratory syncytial virus infection.
doi
10.1186/s12967-024-05677-8
pmid
39313785
authors array · 9 items
[0]
Bochun Cao
[1]
Menglu Li
[2]
Xiaoping Li
[3]
Xianyan Ji
[4]
Lin Wan
[5]
Yingying Jiang
[6]
Lu Zhou
[7]
Fang Gong
[8]
Xiangjie Chen
journal
Journal of translational medicine
year
2024
abstract
BACKGROUND: Respiratory syncytial virus (RSV) is a prominent etiological agent of lower respiratory tract infections in children, responsible for approximately 80% of cases of pediatric bronchiolitis and 50% of cases of infant pneumonia. 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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All data are available and the correspondent can be contacted if requested.
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LY6E and TCN2 are potential peripheral blood diagnostic biomarkers for pediatric RSV infection.
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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).
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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).
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[343]
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[344]
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[352]
GSM5682471
sample_count
353
group_sizes
null
group_sizes_basis
null
platform
25336
taxon
Homo sapiens
title
Whole blood transcriptomics in RSV infected children
resolution_checked_at
2026-11-01T20:16:08Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[3] object · 15 fields
id
data:geo:GSE77087
role
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application/vnd.ncbi.geo-series+json
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https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE77087
sha256
null
bytes
null
access
open
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resolved
reader
null
reader_status
reader_required
identifier
GSE77087
version
null
note
All data are available and the correspondent can be contacted if requested.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
All data are available and the correspondent can be contacted if requested.
access_statement_kind
data_availability_statement
sample_accessions array · 104 items
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GSM2043650
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[67]
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[103]
GSM2043729
sample_count
104
group_sizes
null
group_sizes_basis
null
platform
10558
taxon
Homo sapiens
title
Nasopharyngeal microbiota, host transcriptome and disease severity in children with respiratory syncytial virus infection
resolution_checked_at
2026-11-01T20:16:08Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[4] object · 15 fields
id
data:geo:GSE80179
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raw
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geo-series
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application/vnd.ncbi.geo-series+json
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https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE80179
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null
bytes
null
access
open
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resolved
reader
null
reader_status
reader_required
identifier
GSE80179
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null
note
All data are available and the correspondent can be contacted if requested.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
All data are available and the correspondent can be contacted if requested.
access_statement_kind
data_availability_statement
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sample_count
79
group_sizes
null
group_sizes_basis
null
platform
10558
taxon
Homo sapiens
title
A simple screening approach to prioritize genes for functional analysis identifies a role for IRF7 in the control of RSV disease.
resolution_checked_at
2026-11-01T20:16:08Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
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[2]
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[3]
asset:data:geo:GSE188427 licence not read
[4]
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[5]
asset:data:geo:GSE77087 licence not read
[6]
asset:data:geo:GSE80179 not downloaded
[7]
asset:data:geo:GSE80179 licence not read
analysis object · 4 fields
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complete
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[0] object · 10 fields
id
method-1
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group_comparison
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group_summary
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two_or_more_groups_continuous
evidence object · 3 fields
score
0.8
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high
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analysis of variance
[1] object · 10 fields
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method-2
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differential_expression
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limma_voom
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Differential expression analysis
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[0]
normalise_counts
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missing_operations array · 0 items
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count_matrix_with_condition
evidence object · 3 fields
score
0.8
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limma
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machine_learning
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random_forest
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missing_operations array · 1 item
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machine_learning_random_forest
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false
parameters object · 0 fields
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[0]
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evidence object · 3 fields
score
0.7
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evidence object · 3 fields
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missing_operations array · 0 items
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reference_standard_and_test
evidence object · 3 fields
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capability object · 3 fields
state
complete
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gwas
candidate
Automated Assays Laravel application and simulated adapters
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tier
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capability:computational_analysis
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owned
basis
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data object · 6 fields
tier
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[0]
GSE188427
[1]
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[0]
GSE188427
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statements array · 1 item
[0]
All data are available and the correspondent can be contacted if requested.
basis
The paper names GSE188427, GSE80179, GSE105450, GSE77087 in Gene Expression Omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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source:pmid:39313785
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data:geo:GSE105450
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review object · 5 fields
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partial
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extraction_review
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minimax
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minimax
read_at
2026-11-01T19:32:46Z
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single_reader
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null
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verbatim
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extraction
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pmid:39313785
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source:pmid:39313785
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PMID 39313785 full text
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data:geo:GSE105450
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GEO GSE105450
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[7]
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[0]
ction and further inhibited RSV infection in A549 and BEAS-2B cell lines. Importantly, based o
[1]
l culture, maintenance, and transfection The A549 and BEAS-2B cell lines were purchased from N
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paper_text_order:2497
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39313785", "kind": "science-record", "revision": 3, "content_hash": "sha256:59d8b3807ac91bb0fc6fc6b1028b670e5257e608ca75a06cd458b56909ff043c", "created_at": "2026-11-01T20:29:30Z", "updated_at": "2026-11-01T22:12:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Innovative biomarkers TCN2 and LY6E can significantly inhibit respiratory syncytial virus infection.", "doi": "10.1186/s12967-024-05677-8", "pmid": "39313785", "authors": ["Bochun Cao", "Menglu Li", "Xiaoping Li", "Xianyan Ji", "Lin Wan", "Yingying Jiang", "Lu Zhou", "Fang Gong", "Xiangjie Chen"], "journal": "Journal of translational medicine", "year": 2024, "abstract": "BACKGROUND: Respiratory syncytial virus (RSV) is a prominent etiological agent of lower respiratory tract infections in children, responsible for approximately 80% of cases of pediatric bronchiolitis and 50% of cases of infant pneumonia. 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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