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pmid:36243706

Co-expression network analysis identifies potential candidate hub genes in severe influenza patients needing invasive mechanical ventilation.

Liang Chen · Jie Hua · Xiaopu He

BMC genomics · 2022 doi:10.1186/s12864-022-08915-9

Paper

complete

Experiment

complete

Data

partial

Analysis

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Execution

absent

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2026-11-01T18:15:37Z
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title
Co-expression network analysis identifies potential candidate hub genes in severe influenza patients needing invasive mechanical ventilation.
doi
10.1186/s12864-022-08915-9
pmid
36243706
authors array · 3 items
[0]
Liang Chen
[1]
Jie Hua
[2]
Xiaopu He
journal
BMC genomics
year
2022
abstract
BACKGROUND: Influenza is a contagious disease that affects people of all ages and is linked to considerable mortality during epidemics and occasional outbreaks. Moreover, effective immunological biomarkers are needed for elucidating aetiology and preventing and treating severe influenza. Herein, we aimed to evaluate the key genes linked with the disease severity in influenza patients needing invasive mechanical ventilation (IMV). Three gene microarray data sets (GSE101702, GSE21802, and GSE111368) from blood samples of influenza patients were made available by the Gene Expression Omnibus (GEO) database. The GSE101702 and GSE21802 data sets were combined to create the training set. Hub indicators for IMV patients with severe influenza were determined using differential expression analysis and Weighted correlation network analysis (WGCNA) from the training set. The receiver operating characteristic curve (ROC) was also used to evaluate the hub genes from the test set's diagnostic accuracy. Different immune cells' infiltration levels in the expression profile and their correlation with hub gene markers were examined using single-sample gene set enrichment analysis (ssGSEA). RESULTS: In the present study, we evaluated a total of 447 differential genes. WGCNA identified eight co-expression modules, with the red module having the strongest correlation with IMV patients. Differential genes were combined to obtain 3 hub genes (HLA-DPA1, HLA-DRB3, and CECR1). The identified genes were investigated as potential indicators for patients with severe influenza who required IMV using the least absolute shrinkage and selection operator (LASSO) approach. The ROC showed the diagnostic value of the three hub genes in determining the severity of influenza. Using ssGSEA, it has been revealed that the expression of key genes was negatively correlated with neutrophil activation and positively associated with adaptive cellular immune response. CONCLUSION: We evaluated three novel hub genes that could be linked to the immunopathological mechanism of severe influenza patients who require IMV treatment and could be used as potential biomarkers for severe influenza prevention and treatment.
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The receiver operating characteristic curve (ROC) was also used to evaluate the hub genes from the test set's diagnostic accuracy.
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The receiver operating characteristic curve (ROC) was also used to evaluate the hub genes from the test set's diagnostic accuracy.
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Publicly available datasets were analyzed in this study. These data can be found in GSE101702 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101702), GSE21802 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21802) and GSE111368 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE111368).
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sections[20] "Availability of data and materials" paragraph 2
quote
Publicly available datasets were analyzed in this study. These data can be found in GSE101702 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101702), GSE21802 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21802) and GSE111368 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE111368).
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ROC analysis from the training set showed that area under the ROC curve (AUC) was 0.862 [95% confidence interval (CI) 0.800–0.921] for CECR1, 0.866 (95% CI 0.805–0.919) for HLA-DPA1, and 0.821 (95% CI 0.748–0.886) for HLA-DRB3, accordingly (Fig. 4B).
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ROC analysis from the training set showed that area under the ROC curve (AUC) was 0.862 [95% confidence interval (CI) 0.800–0.921] for CECR1, 0.866 (95% CI 0.805–0.919) for HLA-DPA1, and 0.821 (95% CI 0.748–0.886) for HLA-DRB3, accordingly (Fig. 4B).
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sections[5] "Evaluation of hub gene expression and diagnostic value" paragraph 2
quote
ROC analysis from the training set showed that area under the ROC curve (AUC) was 0.862 [95% confidence interval (CI) 0.800–0.921] for CECR1, 0.866 (95% CI 0.805–0.919) for HLA-DPA1, and 0.821 (95% CI 0.748–0.886) for HLA-DRB3, accordingly (Fig. 4B).
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sections[5] "Evaluation of hub gene expression and diagnostic value" paragraph 2
quote
Meanwhile, the AUC was 0.700–0.800 for the three hub genes from the test set, suggesting a moderate diagnostic accuracy (Fig. 4D).
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ROC analysis from the training set showed that area under the ROC curve (AUC) was 0.862 [95% confidence interval (CI) 0.800–0.921] for CECR1, 0.866 (95% CI 0.805–0.919) for HLA-DPA1, and 0.821 (95% CI 0.748–0.886) for HLA-DRB3, accordingly (Fig. 4B).
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GSM3029691
sample_count
359
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null
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null
platform
10558
taxon
Homo sapiens
title
Progression of whole blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in patients with severe influenza
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[3] object · 15 fields
id
data:geo:GSE21802
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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=GSE21802
sha256
null
bytes
null
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resolved
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null
reader_status
reader_required
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GSE21802
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null
note
Publicly available datasets were analyzed in this study. These data can be found in GSE101702 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101702), GSE21802 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21802) and GSE111368 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE111368).
structure object · 15 fields
repository
GEO
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GEO accession URL
access_statement_verbatim
Publicly available datasets were analyzed in this study. These data can be found in GSE101702 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101702), GSE21802 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21802) and GSE111368 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE111368).
access_statement_kind
data_availability_statement
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GSM542941
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GSM542980
sample_count
40
group_sizes
null
group_sizes_basis
null
platform
6102
taxon
Homo sapiens
title
Hosts responses in critical disease caused by pandemic H1N1
resolution_checked_at
2026-11-01T18:46:34Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 6 items
[0]
asset:data:geo:GSE101702 not downloaded
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asset:data:geo:GSE101702 licence not read
[2]
asset:data:geo:GSE111368 not downloaded
[3]
asset:data:geo:GSE111368 licence not read
[4]
asset:data:geo:GSE21802 not downloaded
[5]
asset:data:geo:GSE21802 licence not read
analysis object · 4 fields
state
partial
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[0] object · 10 fields
id
method-1
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null
specific
null
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receiver operating characteristic curve (ROC) analysis
dsl_operations array · 0 items
missing_operations array · 0 items
parameters object · 0 fields
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evidence object · 3 fields
score
1
band
verbatim
quote
The receiver operating characteristic curve (ROC) was also used to evaluate the hub genes from the test set's diagnostic accuracy.
targets array · 2 items
[0] object · 8 fields
id
target-published-estimate
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claim-target-result
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null
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per cent
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null
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complete
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The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none.
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auc
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null
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complete
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The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none.
gaps array · 1 item
[0]
method.reader_named_unmapped
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
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assay_families array · 9 items
[0]
meta_analysis
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pca
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differential_expression
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gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
blocked
tier
R4
blocking_axis
method
blocked_on
method:not_determinable
axes object · 3 fields
method object · 5 fields
tier
R4
expressible
false
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basis
The reader quoted the method the paper names (receiver operating characteristic curve (ROC) analysis), but the corpus's method extractor could not map it onto a DSL operation, so the method is published but not expressible.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 3 items
[0]
GSE101702
[1]
GSE21802
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GSE111368
resolved_accessions array · 3 items
[0]
GSE101702
[1]
GSE21802
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GSE111368
statements array · 1 item
[0]
Publicly available datasets were analyzed in this study. These data can be found in GSE101702 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101702), GSE21802 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21802) and GSE111368 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE111368).
basis
The paper names GSE101702, GSE21802, GSE111368 in NCBI-GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
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assets array · 2 items
[0]
source:pmid:36243706
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data:geo:GSE101702
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run_analysis
must_build object · 5 fields
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[0]
data:geo:GSE101702
gaps array · 1 item
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method:not_determinable
review object · 5 fields
state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
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MiniMax-M3.1-Flash
provider
minimax
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minimax
read_at
2026-11-01T18:10:55Z
independence
single_reader
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verbatim
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verbatim
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5
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9610
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2074
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paper
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pmid:36243706
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source:pmid:36243706
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manuscript
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PMID 36243706 full text
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data:geo:GSE101702
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dataset
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GEO GSE101702
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classification
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paper
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pmid:36243706
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source:pmid:36243706
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PMID 36243706 full text
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dataset
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GEO GSE101702
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agent:corpus-assay-engine
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extraction
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agent:minimax-reader
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activity-resolve-GSE101702
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accession_resolution
used array · 1 item
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data:geo:GSE101702
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agent:corpus-assay-engine
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agent:corpus-assay-engine
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null
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[0]
ive mechanical ventilation (IMV). Three gene microarray data sets (GSE101702, GSE21802, and GSE11136
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36243706", "kind": "science-record", "revision": 3, "content_hash": "sha256:8fb5d60324102a8a9eaf06b39bacf0f95ce13fd17103aefbfceeea219bb3fe3d", "created_at": "2026-11-01T18:15:37Z", "updated_at": "2026-11-01T21:29:13Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Co-expression network analysis identifies potential candidate hub genes in severe influenza patients needing invasive mechanical ventilation.", "doi": "10.1186/s12864-022-08915-9", "pmid": "36243706", "authors": ["Liang Chen", "Jie Hua", "Xiaopu He"], "journal": "BMC genomics", "year": 2022, "abstract": "BACKGROUND: Influenza is a contagious disease that affects people of all ages and is linked to considerable mortality during epidemics and occasional outbreaks. Moreover, effective immunological biomarkers are needed for elucidating aetiology and preventing and treating severe influenza. Herein, we aimed to evaluate the key genes linked with the disease severity in influenza patients needing invasive mechanical ventilation (IMV). Three gene microarray data sets (GSE101702, GSE21802, and GSE111368) from blood samples of influenza patients were made available by the Gene Expression Omnibus (GEO) database. The GSE101702 and GSE21802 data sets were combined to create the training set. Hub indicators for IMV patients with severe influenza were determined using differential expression analysis and Weighted correlation network analysis (WGCNA) from the training set. The receiver operating characteristic curve (ROC) was also used to evaluate the hub genes from the test set's diagnostic accuracy. Different immune cells' infiltration levels in the expression profile and their correlation with hub gene markers were examined using single-sample gene set enrichment analysis (ssGSEA).\nRESULTS: In the present study, we evaluated a total of 447 differential genes. WGCNA identified eight co-expression modules, with the red module having the strongest correlation with IMV patients. Differential genes were combined to obtain 3 hub genes (HLA-DPA1, HLA-DRB3, and CECR1). The identified genes were investigated as potential indicators for patients with severe influenza who required IMV using the least absolute shrinkage and selection operator (LASSO) approach. The ROC showed the diagnostic value of the three hub genes in determining the severity of influenza. Using ssGSEA, it has been revealed that the expression of key genes was negatively correlated with neutrophil activation and positively associated with adaptive cellular immune response.\nCONCLUSION: We evaluated three novel hub genes that could be linked to the immunopathological mechanism of severe influenza patients who require IMV treatment and could be used as potential biomarkers for severe influenza prevention and treatment.", "claims": [{"id": "claim-method", "statement": "The receiver operating characteristic curve (ROC) was also used to evaluate the hub genes from the test set's diagnostic accuracy.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36243706", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "The receiver operating characteristic curve (ROC) was also used to evaluate the hub genes from the test set's diagnostic accuracy."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. These data can be found in GSE101702 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101702), GSE21802 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21802) and GSE111368 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE111368).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36243706", "locator": "sections[20] \"Availability of data and materials\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. These data can be found in GSE101702 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101702), GSE21802 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21802) and GSE111368 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE111368)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "ROC analysis from the training set showed that area under the ROC curve (AUC) was 0.862 [95% confidence interval (CI) 0.800–0.921] for CECR1, 0.866 (95% CI 0.805–0.919) for HLA-DPA1, and 0.821 (95% CI 0.748–0.886) for HLA-DRB3, accordingly (Fig. 4B).", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "ROC analysis from the training set showed that area under the ROC curve (AUC) was 0.862 [95% confidence interval (CI) 0.800–0.921] for CECR1, 0.866 (95% CI 0.805–0.919) for HLA-DPA1, and 0.821 (95% CI 0.748–0.886) for HLA-DRB3, accordingly (Fig. 4B)."}, "evidence": [{"asset": "source:pmid:36243706", "locator": "sections[5] \"Evaluation of hub gene expression and diagnostic value\" paragraph 2", "quote": "ROC analysis from the training set showed that area under the ROC curve (AUC) was 0.862 [95% confidence interval (CI) 0.800–0.921] for CECR1, 0.866 (95% CI 0.805–0.919) for HLA-DPA1, and 0.821 (95% CI 0.748–0.886) for HLA-DRB3, accordingly (Fig. 4B)."}, {"asset": "source:pmid:36243706", "locator": "sections[5] \"Evaluation of hub gene expression and diagnostic value\" paragraph 2", "quote": "Meanwhile, the AUC was 0.700–0.800 for the three hub genes from the test set, suggesting a moderate diagnostic accuracy (Fig. 4D)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "ROC analysis from the training set showed that area under the ROC curve (AUC) was 0.862 [95% confidence interval (CI) 0.800–0.921] for CECR1, 0.866 (95% CI 0.805–0.919) for HLA-DPA1, and 0.821 (95% CI 0.748–0.886) for HLA-DRB3, accordingly (Fig. 4B).", "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:36243706"], "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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No tolerance is published because the paper states none."}], "gaps": ["method.reader_named_unmapped"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "blocked", "tier": "R4", "blocking_axis": "method", "blocked_on": "method:not_determinable", "axes": {"method": {"tier": "R4", "expressible": false, "required_operations": [], "missing_operations": [], "basis": "The reader quoted the method the paper names (receiver operating characteristic curve (ROC) analysis), but the corpus's method extractor could not map it onto a DSL operation, so the method is published but not expressible."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE101702", "GSE21802", "GSE111368"], "resolved_accessions": ["GSE101702", "GSE21802", "GSE111368"], "statements": ["Publicly available datasets were analyzed in this study. These data can be found in GSE101702 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101702), GSE21802 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE21802) and GSE111368 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE111368)."], "basis": "The paper names GSE101702, GSE21802, GSE111368 in NCBI-GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:36243706", "data:geo:GSE101702"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE101702"]}, "gaps": ["method:not_determinable"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:10:55Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 9610, "completion_tokens": 2074, "cached_tokens": 128}}, "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:36243706", "type": "paper", "label": "pmid:36243706"}, {"id": "source:pmid:36243706", "type": "manuscript", "label": "PMID 36243706 full text"}, {"id": "data:geo:GSE101702", "type": "dataset", "label": "GEO GSE101702"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36243706", "type": "paper", "label": "pmid:36243706"}, {"id": "source:pmid:36243706", "type": "manuscript", "label": "PMID 36243706 full text"}, {"id": "data:geo:GSE101702", "type": "dataset", "label": "GEO GSE101702"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36243706", "type": "extraction", "used": ["source:pmid:36243706"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE101702", "type": "accession_resolution", "used": ["data:geo:GSE101702"], "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:36243706", "parent_hash": "sha256:227e7d9cd64437438d36d9ae777a29a2b6f9d81b18543295cacf87073faa9602", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE101702 licence not read", "asset:data:geo:GSE101702 not downloaded", "asset:data:geo:GSE111368 licence not read", "asset:data:geo:GSE111368 not downloaded", "asset:data:geo:GSE21802 licence not read", "asset:data:geo:GSE21802 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": ["ive mechanical ventilation (IMV). Three gene microarray data sets (GSE101702, GSE21802, and GSE11136"], "order_basis": "paper_text_order:542", "id": "assay:1"}]}