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pmid:40821971

Identification of hub genes and prediction of the ceRNA network in adult sepsis.

Kangyi Xue · Kan Wu · Haoxian Luo · Haihua Luo · Zhaoqian Zhong · Fen Li · Lei Li · Li Chen

PeerJ · 2025 doi:10.7717/peerj.19619

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complete

Experiment

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Data

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title
Identification of hub genes and prediction of the ceRNA network in adult sepsis.
doi
10.7717/peerj.19619
pmid
40821971
authors array · 8 items
[0]
Kangyi Xue
[1]
Kan Wu
[2]
Haoxian Luo
[3]
Haihua Luo
[4]
Zhaoqian Zhong
[5]
Fen Li
[6]
Lei Li
[7]
Li Chen
journal
PeerJ
year
2025
abstract
Background: Sepsis refers to a dysregulated host immune response to infection. It carries a high risk of morbidity and mortality, and its pathogenesis has yet to be fully elucidated. The main aim of this study was to identify prognostic hub genes for sepsis and to predict a competitive endogenous RNA (ceRNA) network that regulates the hub genes. Methods: Six transcriptome datasets from the peripheral blood of septic patients were retrieved from the Gene Expression Omnibus (GEO) database. The robust rank aggregation (RRA) method was used to screen differentially expressed genes (DEGs) across these datasets. A comprehensive bioinformatics investigation was conducted, encompassing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using the "clusterProfiler" package in R, as well as gene set enrichment analysis (GSEA) to further elucidate the biological functions and pathways associated with the DEGs. Weighted gene co-expression network analysis (WGCNA) was performed to identify a module significantly associated with sepsis. Integration of this module with protein-protein interaction (PPI) network analysis facilitated the identification of five hub genes. These hub genes were subsequently validated using an independent dataset and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis of peripheral blood samples from septic patients. The prognostic values of these hub genes were assessed via receiver operating characteristic (ROC) curve analysis. Finally, a ceRNA network regulating the prognostic hub genes was constructed by integrating data from a literature review as well as five online databases. Results: RRA analysis identified 164 DEGs across six training cohorts. Bioinformatics analyses revealed concurrent hyperinflammation and immunosuppression in sepsis patients. Five hub genes were identified via WGCNA and PPI network analysis, and their differential expression was verified by the validation dataset (GSE28750) and RT-qPCR analysis in the peripheral blood of septic patients. ROC analysis confirmed four hub genes with prognostic value, and a ceRNA network was predicted to elucidate their regulatory mechanisms. Conclusion: This study identified four hub genes (CLEC4D, GPR84, S100A12, and HK3) with significant prognostic value in sepsis and predicted a ceRNA network (NEAT1-hsa-miR-495-3p-ELF1) regulating their expression. The integrated analysis reconfirmed the concurrent presence of hyperinflammation and immunosuppression in hospitalized sepsis patients. These findings enhance the understanding of sepsis pathogenesis and identify potential therapeutic targets.
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Statistically changed genes and differentially expressed genes (DEGs) were screened using the robust rank aggregation (RRA) method, which is an unbiased and effective approach for integrating data from diverse chip platforms using a comprehensive ranking list algorithm (Jia & Zhai, 2019; Yan et al., 2018).
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sections[4] "Robust rank aggregation analysis" paragraph 2
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Statistically changed genes and differentially expressed genes (DEGs) were screened using the robust rank aggregation (RRA) method, which is an unbiased and effective approach for integrating data from diverse chip platforms using a comprehensive ranking list algorithm (Jia & Zhai, 2019; Yan et al., 2018).
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sections[29] "Additional Information and Declarations" paragraph 6
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The datasets are available at GEO: GSE137340, GSE69063, GSE69528, GSE54514, GSE57065, GSE95233, and GSE28570.
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This study identified four hub genes (CLEC4D, GPR84, S100A12, and HK3) with significant prognostic value in sepsis and predicted a ceRNA network (NEAT1-hsa-miR-495-3p-ELF1) regulating their expression.
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This study identified four hub genes (CLEC4D, GPR84, S100A12, and HK3) with significant prognostic value in sepsis and predicted a ceRNA network (NEAT1-hsa-miR-495-3p-ELF1) regulating their expression.
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This study identified four hub genes (CLEC4D, GPR84, S100A12, and HK3) with significant prognostic value in sepsis and predicted a ceRNA network (NEAT1-hsa-miR-495-3p-ELF1) regulating their expression.
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[106]
GSM1374020
sample_count
107
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Early and dynamic changes in gene expression in septic shock patients: a genome wide approach
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[5] object · 15 fields
id
data:geo:GSE69063
role
raw
format
geo-series
media_type
application/vnd.ncbi.geo-series+json
uri
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE69063
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE69063
version
null
note
The datasets are available at GEO: GSE137340, GSE69063, GSE69528, GSE54514, GSE57065, GSE95233, and GSE28570.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets are available at GEO: GSE137340, GSE69063, GSE69528, GSE54514, GSE57065, GSE95233, and GSE28570.
access_statement_kind
data_availability_statement
sample_accessions array · 153 items
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[113]
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[114]
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[119]
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[120]
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[122]
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[127]
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[130]
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[134]
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[135]
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[136]
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[137]
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[138]
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[140]
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[141]
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[146]
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[147]
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[148]
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[149]
GSM1691837
[150]
GSM1691838
[151]
GSM1691839
[152]
GSM1691840
sample_count
153
group_sizes
null
group_sizes_basis
null
platform
19983
taxon
Homo sapiens
title
Gene expression patterns in blood during human anaphylaxis, trauma, and sepsis
resolution_checked_at
2026-11-01T20:16:08Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[6] object · 15 fields
id
data:geo:GSE69528
role
raw
format
geo-series
media_type
application/vnd.ncbi.geo-series+json
uri
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE69528
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE69528
version
null
note
The datasets are available at GEO: GSE137340, GSE69063, GSE69528, GSE54514, GSE57065, GSE95233, and GSE28570.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets are available at GEO: GSE137340, GSE69063, GSE69528, GSE54514, GSE57065, GSE95233, and GSE28570.
access_statement_kind
data_availability_statement
sample_accessions array · 138 items
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[1]
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[24]
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[25]
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[26]
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[32]
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[33]
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[34]
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[35]
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[37]
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[39]
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[40]
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[42]
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[44]
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[45]
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[50]
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[53]
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[54]
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[55]
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[56]
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[58]
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[60]
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[61]
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[62]
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[63]
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[64]
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[65]
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[66]
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[67]
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[68]
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[69]
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[70]
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[71]
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[72]
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[73]
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[74]
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[75]
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[76]
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[77]
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[78]
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[81]
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[82]
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[84]
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[85]
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[86]
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[87]
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[88]
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[89]
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[91]
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[92]
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[94]
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[95]
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[96]
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[97]
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[98]
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[99]
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[100]
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[101]
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[102]
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[103]
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[104]
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[105]
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[106]
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[107]
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[108]
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[109]
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[110]
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[111]
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[112]
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[113]
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[114]
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[115]
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[116]
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[118]
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[119]
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[123]
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[125]
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[128]
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[129]
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[130]
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[132]
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[133]
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[134]
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[135]
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[136]
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[137]
GSM1703025
sample_count
138
group_sizes
null
group_sizes_basis
null
platform
10558
taxon
Homo sapiens
title
A Blood Transcriptional Diagnostic Assay for Septicemic Melioidosis
resolution_checked_at
2026-11-01T20:16:08Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[7] object · 15 fields
id
data:geo:GSE95233
role
raw
format
geo-series
media_type
application/vnd.ncbi.geo-series+json
uri
https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE95233
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE95233
version
null
note
The datasets are available at GEO: GSE137340, GSE69063, GSE69528, GSE54514, GSE57065, GSE95233, and GSE28570.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets are available at GEO: GSE137340, GSE69063, GSE69528, GSE54514, GSE57065, GSE95233, and GSE28570.
access_statement_kind
data_availability_statement
sample_accessions array · 124 items
[0]
GSM2500349
[1]
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[2]
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[3]
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[4]
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[30]
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[33]
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[34]
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[35]
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[37]
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[38]
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[39]
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[40]
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[41]
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[42]
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[44]
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[45]
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[55]
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[59]
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[83]
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[84]
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[86]
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[87]
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[93]
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[94]
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[99]
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[100]
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[101]
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[102]
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[103]
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[104]
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[105]
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[106]
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[107]
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[108]
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[109]
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[110]
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[111]
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[113]
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[114]
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[115]
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[116]
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[119]
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[120]
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[121]
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[122]
GSM2500471
[123]
GSM2500472
sample_count
124
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Fractalkine receptor CX3CR1 and leukocyte Ig-like receptor B2 LILRB2 are prognostic biomarkers in septic shock
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 14 items
[0]
asset:data:geo:GSE137340 not downloaded
[1]
asset:data:geo:GSE137340 licence not read
[2]
asset:data:geo:GSE28750 not downloaded
[3]
asset:data:geo:GSE28750 licence not read
[4]
asset:data:geo:GSE54514 not downloaded
[5]
asset:data:geo:GSE54514 licence not read
[6]
asset:data:geo:GSE57065 not downloaded
[7]
asset:data:geo:GSE57065 licence not read
[8]
asset:data:geo:GSE69063 not downloaded
[9]
asset:data:geo:GSE69063 licence not read
[10]
asset:data:geo:GSE69528 not downloaded
[11]
asset:data:geo:GSE69528 licence not read
[12]
asset:data:geo:GSE95233 not downloaded
[13]
asset:data:geo:GSE95233 licence not read
analysis object · 4 fields
state
partial
methods array · 5 items
[0] object · 10 fields
id
method-1
family
clustering
specific
hierarchical
label
Clustering
dsl_operations array · 1 item
[0]
hierarchical_cluster
missing_operations array · 0 items
parameters object · 1 field
n_clusters
clustering tree showing 11 cluster modules
data_shapes array · 1 item
[0]
feature_matrix
evidence object · 3 fields
score
0.8
band
high
quote
Hierarchical clustering
[1] object · 10 fields
id
method-2
family
network_analysis
specific
ppi_network
label
Network / pathway analysis
dsl_operations array · 3 items
[0]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
edge_list
evidence object · 3 fields
score
0.7
band
medium
quote
protein-protein interaction
[2] object · 10 fields
id
method-3
family
network_analysis
specific
pathway_enrichment
label
Network / pathway analysis
dsl_operations array · 1 item
[0]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
edge_list
evidence object · 3 fields
score
0.7
band
medium
quote
pathway enrichment
[3] object · 10 fields
id
method-4
family
diagnostic_evaluation
specific
roc
label
Diagnostic test evaluation
dsl_operations array · 6 items
[0]
confusion_counts
[1]
roc_curve
[2]
sensitivity_specificity
[3]
solve_confusion_matrix
[4]
classification_metrics
[5]
published_precision_envelope
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
reference_standard_and_test
evidence object · 3 fields
score
0.7
band
medium
quote
ROC analysis
[4] object · 10 fields
id
method-5
family
null
specific
null
label
robust rank aggregation (RRA) method
dsl_operations array · 0 items
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 0 items
evidence object · 3 fields
score
1
band
verbatim
quote
Statistically changed genes and differentially expressed genes (DEGs) were screened using the robust rank aggregation (RRA) method, which is an unbiased and effective approach for integrating data from diverse chip platforms using a comprehensive ranking list algorithm (Jia & Zhai, 2019; Yan et al., 2018).
targets array · 0 items
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
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 1 item
[0]
hierarchical_cluster
missing_operations array · 0 items
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: hierarchical.
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 · 7 items
[0]
GSE137340
[1]
GSE69063
[2]
GSE69528
[3]
GSE54514
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The datasets are available at GEO: GSE137340, GSE69063, GSE69528, GSE54514, GSE57065, GSE95233, and GSE28570.
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. The present study systematically retrieved microarray datasets based on the following terms: ‘Seps
[1]
rms: ‘Sepsis’, ‘Adult’, ‘Homo sapiens’, and ‘Microarray’. Datasets were acquired based on the follow
[2]
or Bioconductor (https://bioconductor.org/). Microarray information. Peripheral blood samples from p
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l care and housing SPF-grade C57BL/6 healthy mice were purchased from Southern Medical University.
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days prior to the start of the experiments. Mice were provided ordinary Specific Pathogen Free (SP
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water freely throughout the experiment. All mice were housed in units of equal size and material a
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40821971", "kind": "science-record", "revision": 3, "content_hash": "sha256:65395142619fcb6264e0fc2dc3e92ca0fd260054d060c8d31b7e7699b23410d1", "created_at": "2026-11-01T20:30:54Z", "updated_at": "2026-11-01T22:14:34Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of hub genes and prediction of the ceRNA network in adult sepsis.", "doi": "10.7717/peerj.19619", "pmid": "40821971", "authors": ["Kangyi Xue", "Kan Wu", "Haoxian Luo", "Haihua Luo", "Zhaoqian Zhong", "Fen Li", "Lei Li", "Li Chen"], "journal": "PeerJ", "year": 2025, "abstract": "Background: Sepsis refers to a dysregulated host immune response to infection. It carries a high risk of morbidity and mortality, and its pathogenesis has yet to be fully elucidated. The main aim of this study was to identify prognostic hub genes for sepsis and to predict a competitive endogenous RNA (ceRNA) network that regulates the hub genes.\nMethods: Six transcriptome datasets from the peripheral blood of septic patients were retrieved from the Gene Expression Omnibus (GEO) database. The robust rank aggregation (RRA) method was used to screen differentially expressed genes (DEGs) across these datasets. A comprehensive bioinformatics investigation was conducted, encompassing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses using the \"clusterProfiler\" package in R, as well as gene set enrichment analysis (GSEA) to further elucidate the biological functions and pathways associated with the DEGs. Weighted gene co-expression network analysis (WGCNA) was performed to identify a module significantly associated with sepsis. Integration of this module with protein-protein interaction (PPI) network analysis facilitated the identification of five hub genes. These hub genes were subsequently validated using an independent dataset and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis of peripheral blood samples from septic patients. The prognostic values of these hub genes were assessed via receiver operating characteristic (ROC) curve analysis. Finally, a ceRNA network regulating the prognostic hub genes was constructed by integrating data from a literature review as well as five online databases.\nResults: RRA analysis identified 164 DEGs across six training cohorts. Bioinformatics analyses revealed concurrent hyperinflammation and immunosuppression in sepsis patients. Five hub genes were identified via WGCNA and PPI network analysis, and their differential expression was verified by the validation dataset (GSE28750) and RT-qPCR analysis in the peripheral blood of septic patients. ROC analysis confirmed four hub genes with prognostic value, and a ceRNA network was predicted to elucidate their regulatory mechanisms.\nConclusion: This study identified four hub genes (CLEC4D, GPR84, S100A12, and HK3) with significant prognostic value in sepsis and predicted a ceRNA network (NEAT1-hsa-miR-495-3p-ELF1) regulating their expression. The integrated analysis reconfirmed the concurrent presence of hyperinflammation and immunosuppression in hospitalized sepsis patients. These findings enhance the understanding of sepsis pathogenesis and identify potential therapeutic targets.", "claims": [{"id": "claim-method", "statement": "Statistically changed genes and differentially expressed genes (DEGs) were screened using the robust rank aggregation (RRA) method, which is an unbiased and effective approach for integrating data from diverse chip platforms using a comprehensive ranking list algorithm (Jia & Zhai, 2019; Yan et al., 2018).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40821971", "locator": "sections[4] \"Robust rank aggregation analysis\" paragraph 2", "quote": "Statistically changed genes and differentially expressed genes (DEGs) were screened using the robust rank aggregation (RRA) method, which is an unbiased and effective approach for integrating data from diverse chip platforms using a comprehensive ranking list algorithm (Jia & Zhai, 2019; Yan et al., 2018)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets are available at GEO: GSE137340, GSE69063, GSE69528, GSE54514, GSE57065, GSE95233, and GSE28570.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40821971", "locator": "sections[29] \"Additional Information and Declarations\" paragraph 6", "quote": "The datasets are available at GEO: GSE137340, GSE69063, GSE69528, GSE54514, GSE57065, GSE95233, and GSE28570."}], "state": "complete"}, {"id": "claim-target-result", "statement": "This study identified four hub genes (CLEC4D, GPR84, S100A12, and HK3) with significant prognostic value in sepsis and predicted a ceRNA network (NEAT1-hsa-miR-495-3p-ELF1) regulating their expression.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40821971", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "This study identified four hub genes (CLEC4D, GPR84, S100A12, and HK3) with significant prognostic value in sepsis and predicted a ceRNA network (NEAT1-hsa-miR-495-3p-ELF1) regulating their expression."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "This study identified four hub genes (CLEC4D, GPR84, S100A12, and HK3) with significant prognostic value in sepsis and predicted a ceRNA network (NEAT1-hsa-miR-495-3p-ELF1) regulating their expression.", "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:40821971"], "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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The present study systematically retrieved microarray datasets based on the following terms: ‘Seps", "rms: ‘Sepsis’, ‘Adult’, ‘Homo sapiens’, and ‘Microarray’. Datasets were acquired based on the follow", "or Bioconductor (https://bioconductor.org/). Microarray information. Peripheral blood samples from p"], "order_basis": "paper_text_order:2976", "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": ["l care and housing SPF-grade C57BL/6 healthy mice were purchased from Southern Medical University.", "days prior to the start of the experiments. Mice were provided ordinary Specific Pathogen Free (SP", "water freely throughout the experiment. All mice were housed in units of equal size and material a", "tory Animals. 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