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pmid:40901831

Identification of immune-related biomarkers associated with allergic rhinitis and development of a sample diagnostic model.

MaoMeng Wang · Shuang Wang · XinHua Lin · XiaoJing Lv · XueXia Liu · Hua Zhang

PloS one · 2025 doi:10.1371/journal.pone.0329549

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
id
pmid:40901831
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science-record
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sha256:73cc82987c7aaca1796cffdb8c3646005c69436942c681e54fda407124ad0a1c
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https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json
created_at
2026-11-01T20:31:01Z
updated_at
2026-11-01T22:14:40Z
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paper object · 10 fields
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title
Identification of immune-related biomarkers associated with allergic rhinitis and development of a sample diagnostic model.
doi
10.1371/journal.pone.0329549
pmid
40901831
authors array · 6 items
[0]
MaoMeng Wang
[1]
Shuang Wang
[2]
XinHua Lin
[3]
XiaoJing Lv
[4]
XueXia Liu
[5]
Hua Zhang
journal
PloS one
year
2025
abstract
This study was designed to identify immune-related biomarkers associated with allergic rhinitis (AR) and construct a robust a diagnostic model. Two datasets (GSE5010 and GSE50223) were downloaded from the NCBI GEO database, containing 38 and 84 blood CD4 + T cell samples, respectively. To eliminate batch effects, the surrogate variable analysis (sva) R package (version 3.38.0) was employed, enabling the integration of data for subsequent analysis. Immune cell infiltration profiles were assessed using the Gene Set Variation Analysis (GSVA) R package (version 1.36.3). A gene co-expression network was constructed via the Weighted Gene Co-Expression Network Analysis (WGCNA) algorithm to identify disease-related modules. Differentially expressed genes (DEGs) were identified using the linear models for microarray data (limma) R package (version 3.34.7), followed by functional enrichment analysis using DAVID. Protein-protein interaction (PPI) networks were constructed based on the STRING database to highlight key genes. A diagnostic model was subsequently developed utilizing the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm and Support Vector Machine (SVM) method, with its discriminative capacity assessed via Receiver Operating Characteristic (ROC) curves. A total of twenty-eight immune cell types were analyzed, revealing significant differences in eight types between the AR and control groups. Through WGCNA, three disease-related modules comprising 4278 candidate genes were identified. Differential expression analysis identified 326 significant DEGs, of which 257 overlapped with WGCNA-selected genes. These genes exhibited significant enrichment in immune-related pathways, including "cytokine-cytokine receptor interaction" and "chemokine signaling pathway." Gene Set Enrichment Analysis (GSEA) further uncovered 12 KEGG pathways significantly associated with disease risk scores. Drug screening identified 24 small molecule drugs related to key genes. A diagnostic model incorporating five genes (RFC4, LYN, IL3, TNFRSF1B, and RBBP7) was constructed, demonstrating diagnostic efficiencies of 0.843 and 0.739 in the training and validation sets, respectively. An AR mouse model was successfully established, and the expression levels of relevant genes were validated through RT-qPCR experiments. The five-gene diagnostic model established in this study exhibits strong predictive ability in distinguishing AR patients from healthy controls, with potential clinical applications in diagnosing AR and advancing novel diagnostic and therapeutic strategies.
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To eliminate batch effects, the surrogate variable analysis (sva) R package (version 3.38.0) was employed, enabling the integration of data for subsequent analysis.
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To eliminate batch effects, the surrogate variable analysis (sva) R package (version 3.38.0) was employed, enabling the integration of data for subsequent analysis.
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Two datasets were downloaded from NCBI GEO database [13] for analysis: GSE5010 [14], which consists of 38 human blood-extracted CD4 + T cell samples (18 AR [Allergic Rhinitis] patients and 20 from CTRL [Control] subjects), with the detection platform being the GPL10558 Illumina HumanHT-12 V4.0 expression beadchip; and GSE50223, which contains 84 human blood CD4 + T cell samples (42 from AR patients and 42 from CTRL subjects), with the detection platform being the GPL6884 Illumina HumanWG-6 v3.0 expression beadchip.
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sections[3] "2.1 Data set acquisition and batch correction" paragraph 2
quote
Two datasets were downloaded from NCBI GEO database [13] for analysis: GSE5010 [14], which consists of 38 human blood-extracted CD4 + T cell samples (18 AR [Allergic Rhinitis] patients and 20 from CTRL [Control] subjects), with the detection platform being the GPL10558 Illumina HumanHT-12 V4.0 expression beadchip; and GSE50223, which contains 84 human blood CD4 + T cell samples (42 from AR patients and 42 from CTRL subjects), with the detection platform being the GPL6884 Illumina HumanWG-6 v3.0 expression beadchip.
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A diagnostic model incorporating five genes (RFC4, LYN, IL3, TNFRSF1B, and RBBP7) was constructed, demonstrating diagnostic efficiencies of 0.843 and 0.739 in the training and validation sets, respectively.
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sections[0] "Abstract" paragraph 1
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A diagnostic model incorporating five genes (RFC4, LYN, IL3, TNFRSF1B, and RBBP7) was constructed, demonstrating diagnostic efficiencies of 0.843 and 0.739 in the training and validation sets, respectively.
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A diagnostic model incorporating five genes (RFC4, LYN, IL3, TNFRSF1B, and RBBP7) was constructed, demonstrating diagnostic efficiencies of 0.843 and 0.739 in the training and validation sets, respectively.
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Two datasets were downloaded from NCBI GEO database [13] for analysis: GSE5010 [14], which consists of 38 human blood-extracted CD4 + T cell samples (18 AR [Allergic Rhinitis] patients and 20 from CTRL [Control] subjects), with the detection platform being the GPL10558 Illumina HumanHT-12 V4.0 expression beadchip; and GSE50223, which contains 84 human blood CD4 + T cell samples (42 from AR patients and 42 from CTRL subjects), with the detection platform being the GPL6884 Illumina HumanWG-6 v3.0 expression beadchip.
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Two datasets were downloaded from NCBI GEO database [13] for analysis: GSE5010 [14], which consists of 38 human blood-extracted CD4 + T cell samples (18 AR [Allergic Rhinitis] patients and 20 from CTRL [Control] subjects), with the detection platform being the GPL10558 Illumina HumanHT-12 V4.0 expression beadchip; and GSE50223, which contains 84 human blood CD4 + T cell samples (42 from AR patients and 42 from CTRL subjects), with the detection platform being the GPL6884 Illumina HumanWG-6 v3.0 expression beadchip.
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Global gene expression of nasal epithelial cells in patients with seasonal allergic rhinitis
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Two datasets were downloaded from NCBI GEO database [13] for analysis: GSE5010 [14], which consists of 38 human blood-extracted CD4 + T cell samples (18 AR [Allergic Rhinitis] patients and 20 from CTRL [Control] subjects), with the detection platform being the GPL10558 Illumina HumanHT-12 V4.0 expression beadchip; and GSE50223, which contains 84 human blood CD4 + T cell samples (42 from AR patients and 42 from CTRL subjects), with the detection platform being the GPL6884 Illumina HumanWG-6 v3.0 expression beadchip.
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Two datasets were downloaded from NCBI GEO database [13] for analysis: GSE5010 [14], which consists of 38 human blood-extracted CD4 + T cell samples (18 AR [Allergic Rhinitis] patients and 20 from CTRL [Control] subjects), with the detection platform being the GPL10558 Illumina HumanHT-12 V4.0 expression beadchip; and GSE50223, which contains 84 human blood CD4 + T cell samples (42 from AR patients and 42 from CTRL subjects), with the detection platform being the GPL6884 Illumina HumanWG-6 v3.0 expression beadchip.
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Amblyomma americanum
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Gene expression changes in feeding female and male lone star ticks, Amblyomma americanum (L)
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Two datasets were downloaded from NCBI GEO database [13] for analysis: GSE5010 [14], which consists of 38 human blood-extracted CD4 + T cell samples (18 AR [Allergic Rhinitis] patients and 20 from CTRL [Control] subjects), with the detection platform being the GPL10558 Illumina HumanHT-12 V4.0 expression beadchip; and GSE50223, which contains 84 human blood CD4 + T cell samples (42 from AR patients and 42 from CTRL subjects), with the detection platform being the GPL6884 Illumina HumanWG-6 v3.0 expression beadchip.
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Two datasets were downloaded from NCBI GEO database [13] for analysis: GSE5010 [14], which consists of 38 human blood-extracted CD4 + T cell samples (18 AR [Allergic Rhinitis] patients and 20 from CTRL [Control] subjects), with the detection platform being the GPL10558 Illumina HumanHT-12 V4.0 expression beadchip; and GSE50223, which contains 84 human blood CD4 + T cell samples (42 from AR patients and 42 from CTRL subjects), with the detection platform being the GPL6884 Illumina HumanWG-6 v3.0 expression beadchip.
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Homo sapiens
title
Allergen challenged CD4+ cells from allergic patients and healthy controls
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To eliminate batch effects, the surrogate variable analysis (sva) R package (version 3.38.0) was employed, enabling the integration of data for subsequent analysis.
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Two datasets were downloaded from NCBI GEO database [13] for analysis: GSE5010 [14], which consists of 38 human blood-extracted CD4 + T cell samples (18 AR [Allergic Rhinitis] patients and 20 from CTRL [Control] subjects), with the detection platform being the GPL10558 Illumina HumanHT-12 V4.0 expression beadchip; and GSE50223, which contains 84 human blood CD4 + T cell samples (42 from AR patients and 42 from CTRL subjects), with the detection platform being the GPL6884 Illumina HumanWG-6 v3.0 expression beadchip.
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The paper names GSE5010, GSE50223, GSE43523 in NCBI GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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source:pmid:40901831
agent
agent:minimax-reader
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activity-resolve-GSE43523
type
accession_resolution
used array · 1 item
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data:geo:GSE43523
agent
agent:corpus-assay-engine
agents array · 2 items
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agent:corpus-assay-engine
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software
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agent:minimax-reader
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software
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MiniMax literature reader
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dsl_catalogue_fingerprint
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capability_table_fingerprint
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lineage object · 4 fields
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gaps array · 11 items
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asset:data:geo:GSE43523 licence not read
[1]
asset:data:geo:GSE43523 not downloaded
[2]
asset:data:geo:GSE5010 licence not read
[3]
asset:data:geo:GSE5010 not downloaded
[4]
asset:data:geo:GSE50223 licence not read
[5]
asset:data:geo:GSE50223 not downloaded
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execution.not_run
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method.reader_named_unmapped
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review.human_critique
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review.independent_reader
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review.machine_critique
assays array · 4 items
[0] object · 11 fields
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data_generation
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microarray
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99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.93
evidence array · 1 item
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were identified using the linear models for microarray data (limma) R package (version 3.34.7), fol
order_basis
paper_text_order:888
id
assay:1
[1] object · 11 fields
role
data_generation
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animal_model
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99e1195c7d6f
required_operations array · 0 items
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[0]
ing and validation sets, respectively. An AR mouse model was successfully established, and the expres
[1]
ing and validation sets, respectively. An AR mouse model was successfully established, and the
[2]
equent experiments. Meanwhile, the remaining mouse heads were fixed in a 4% paraformaldehyde so
order_basis
paper_text_order:2298
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assay:2
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99e1195c7d6f
confidence
0.99
evidence array · 2 items
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els of relevant genes were validated through RT-qPCR experiments. The five-gene diagnostic model
[1]
of relevant genes were validated through RT-qPCR experiments. The five-gene diagnostic model
order_basis
paper_text_order:2407
id
assay:3
[3] object · 11 fields
role
analysis
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Complete file
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Two datasets (GSE5010 and GSE50223) were downloaded from the NCBI GEO database, containing 38 and 84 blood CD4 + T cell samples, respectively. To eliminate batch effects, the surrogate variable analysis (sva) R package (version 3.38.0) was employed, enabling the integration of data for subsequent analysis. Immune cell infiltration profiles were assessed using the Gene Set Variation Analysis (GSVA) R package (version 1.36.3). A gene co-expression network was constructed via the Weighted Gene Co-Expression Network Analysis (WGCNA) algorithm to identify disease-related modules. Differentially expressed genes (DEGs) were identified using the linear models for microarray data (limma) R package (version 3.34.7), followed by functional enrichment analysis using DAVID. Protein-protein interaction (PPI) networks were constructed based on the STRING database to highlight key genes. A diagnostic model was subsequently developed utilizing the Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm and Support Vector Machine (SVM) method, with its discriminative capacity assessed via Receiver Operating Characteristic (ROC) curves. A total of twenty-eight immune cell types were analyzed, revealing significant differences in eight types between the AR and control groups. Through WGCNA, three disease-related modules comprising 4278 candidate genes were identified. Differential expression analysis identified 326 significant DEGs, of which 257 overlapped with WGCNA-selected genes. These genes exhibited significant enrichment in immune-related pathways, including \"cytokine-cytokine receptor interaction\" and \"chemokine signaling pathway.\" Gene Set Enrichment Analysis (GSEA) further uncovered 12 KEGG pathways significantly associated with disease risk scores. Drug screening identified 24 small molecule drugs related to key genes. A diagnostic model incorporating five genes (RFC4, LYN, IL3, TNFRSF1B, and RBBP7) was constructed, demonstrating diagnostic efficiencies of 0.843 and 0.739 in the training and validation sets, respectively. An AR mouse model was successfully established, and the expression levels of relevant genes were validated through RT-qPCR experiments. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE5010", "GSE50223", "GSE43523"], "resolved_accessions": ["GSE5010", "GSE50223", "GSE43523"], "statements": ["Two datasets were downloaded from NCBI GEO database [13] for analysis: GSE5010 [14], which consists of 38 human blood-extracted CD4 + T cell samples (18 AR [Allergic Rhinitis] patients and 20 from CTRL [Control] subjects), with the detection platform being the GPL10558 Illumina HumanHT-12 V4.0 expression beadchip; and GSE50223, which contains 84 human blood CD4 + T cell samples (42 from AR patients and 42 from CTRL subjects), with the detection platform being the GPL6884 Illumina HumanWG-6 v3.0 expression beadchip."], "basis": "The paper names GSE5010, GSE50223, GSE43523 in NCBI GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:40901831", "data:geo:GSE43523"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE43523"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T20:01:06Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 5, "usage": {"prompt_tokens": 10434, "completion_tokens": 2144, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:40901831", "type": "paper", "label": "pmid:40901831"}, {"id": "source:pmid:40901831", "type": "manuscript", "label": "PMID 40901831 full text"}, {"id": "data:geo:GSE43523", "type": "dataset", "label": "GEO GSE43523"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40901831", "type": "paper", "label": "pmid:40901831"}, {"id": "source:pmid:40901831", "type": "manuscript", "label": "PMID 40901831 full text"}, {"id": "data:geo:GSE43523", "type": "dataset", "label": "GEO GSE43523"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40901831", "type": "extraction", "used": ["source:pmid:40901831"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE43523", "type": "accession_resolution", "used": ["data:geo:GSE43523"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:40901831", "parent_hash": "sha256:60ddfc6dfeb0aadd456fe44a0d6ac79c71c5cd9f91d567525503d9a534b90cbb", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE43523 licence not read", "asset:data:geo:GSE43523 not downloaded", "asset:data:geo:GSE5010 licence not read", "asset:data:geo:GSE5010 not downloaded", "asset:data:geo:GSE50223 licence not read", "asset:data:geo:GSE50223 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["were identified using the linear models for microarray data (limma) R package (version 3.34.7), fol"], "order_basis": "paper_text_order:888", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ing and validation sets, respectively. An AR mouse model was successfully established, and the expres", "ing and validation sets, respectively. An AR mouse model was successfully established, and the", "equent experiments. Meanwhile, the remaining mouse heads were fixed in a 4% paraformaldehyde so"], "order_basis": "paper_text_order:2298", "id": "assay:2"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["els of relevant genes were validated through RT-qPCR experiments. The five-gene diagnostic model", "of relevant genes were validated through RT-qPCR experiments. 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