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pmid:34354366

Identification of Hub Genes Associated with the Pathogenesis of Intracranial Aneurysm via Integrated Bioinformatics Analysis.

Aifang Zhong · Ning Ding · Yang Zhou · Guifang Yang · Zhenyu Peng · Hongliang Zhang · Xiangping Chai

International journal of general medicine · 2021 doi:10.2147/IJGM.S320396

Paper

complete

Experiment

complete

Data

partial

Analysis

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Execution

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:34354366
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science-record
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2026-11-01T15:41:47Z
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paper object · 10 fields
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title
Identification of Hub Genes Associated with the Pathogenesis of Intracranial Aneurysm via Integrated Bioinformatics Analysis.
doi
10.2147/IJGM.S320396
pmid
34354366
authors array · 7 items
[0]
Aifang Zhong
[1]
Ning Ding
[2]
Yang Zhou
[3]
Guifang Yang
[4]
Zhenyu Peng
[5]
Hongliang Zhang
[6]
Xiangping Chai
journal
International journal of general medicine
year
2021
abstract
BACKGROUND: At present, the pathogenesis of intracranial aneurysms (IA) remains unclear, which significantly hinders the development of novel strategies for the clinical treatment. In this study, bioinformatics methods were used to identify the potential hub genes and pathways associated with the pathogenesis of IA. METHODS: The gene expression datasets of patients with intracranial aneurysm were downloaded from the Gene Expression Database (GEO), and the different data sets were integrated by the robust rank aggregation (RRA) method to identify the differentially expressed genes between patients with intracranial aneurysm and the controls. The functional enrichment analyses of the significant differentially expressed genes (DEGs) were performed and the protein-protein interaction (PPI) network was constructed; thereafter, the hub genes were screened by cytoHubba plug-in of Cytoscape, and finally sequencing dataset GSE122897 was used to verify the hub genes. RESULTS: The GSE15629, GSE75436, GSE26969, and GSE6551 expression profiles have been included in this study, including 34 intracranial aneurysm samples and 26 control samples. The four datasets obtained 136 significant DEGs (45 up-regulated, 91 down-regulated). Enrichment analysis showed that the extracellular matrix structural constituent and the ECM-receptor interaction were closely related to the occurrence of IA. It was finally determined that eight hub genes associated with the development of IA, including VCAN, COL1A1, COL11A1, COL5A1, COL5A2, POSTN, THBS2, and CDH2. CONCLUSION: The discovery of potential hub genes and pathways could enhance the understanding of the molecular mechanisms associated with the development of IA. These hub genes may be potential therapeutic targets for the management and new biomarker for the diagnosis of IA.
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Next, the package of “limma” in R software was used to identify the DEGs.
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sections[4] "Identification of DEGs in IA" paragraph 2
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Next, the package of “limma” in R software was used to identify the DEGs.
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All datasets used and analyzed in the current research are available from the Gene Expression Omnibus GEO (http://www.ncbi.nlm.nih.gov/geo).
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sections[19] "Data Statement and Linking" paragraph 2
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All datasets used and analyzed in the current research are available from the Gene Expression Omnibus GEO (http://www.ncbi.nlm.nih.gov/geo).
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RNA Sequencing Analysis of Intracranial Aneurysm Walls Reveals Involvement of Lysosomes and Immunoglobulins in Rupture
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GSM391282
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Global expression profiling of ruptured and unruptured human intracranial aneurysms
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GSM663774
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Homo sapiens
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Transcriptome-wide characterization of gene expression associated with unruptured intracranial aneurysms
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GSM151660
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GSM151661
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GSM151662
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GSM151664
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2507;570
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Homo sapiens
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Expression data from intracranial arteries and intracranial aneurysms
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2026-11-01T15:39:55Z
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All datasets used and analyzed in the current research are available from the Gene Expression Omnibus GEO (http://www.ncbi.nlm.nih.gov/geo).
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All datasets used and analyzed in the current research are available from the Gene Expression Omnibus GEO (http://www.ncbi.nlm.nih.gov/geo).
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570
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Expression data of Intracranial aneurysm
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Information on Included Datasets
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Table 1
caption
Characteristics of the Included Microarray Datasets
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[0] array · 6 items
[0]
GSE ID
[1]
Participants
[2]
Tissues
[3]
Analysis Type
[4]
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[5]
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[1] array · 6 items
[0]
GSE15629
[1]
14 cases and 5 controls
[2]
Artery
[3]
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[4]
GPL6244
[5]
2010
[2] array · 6 items
[0]
GSE75436
[1]
15 cases and 15 controls
[2]
Artery
[3]
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[4]
GPL570
[5]
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GSE26969
[1]
3 cases and 3 controls
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GPL570
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[0]
GSE6551
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[5]
2007
locator
section[10]/table-wrap[1]#t0001
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GO Analysis of Integrated DEGs
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Functional Enrichment Analysis of Significantly Different Genes
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caption
GO Analysis of Integrated DEGs
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[1]
Description
[2]
P value
[3]
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[1] array · 4 items
[0]
GO:0005201
[1]
Extracellular matrix structural constituent
[2]
9.02E-14
[3]
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[3]
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GO:0005539
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[3]
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[5] array · 4 items
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[1]
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0.001221
[3]
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GO:0048407
[1]
Platelet-derived growth factor binding
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[3]
COL1A1/COL5A1
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[0]
GO:0030674
[1]
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0.001275
[3]
COL11A1/STON2/FLRT3/SORBS1/SYNPO2/MPP7
[8] array · 4 items
[0]
GO:0008201
[1]
Heparin binding
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0.00146
[3]
POSTN/THBS2/COL11A1/COL5A1/ABI3BP
[9] array · 4 items
[0]
GO:0086080
[1]
Protein binding involved in heterotypic cell-cell adhesion
[2]
0.001791
[3]
DSP/GLDN
[10] array · 4 items
[0]
GO:1901681
[1]
Sulfur compound binding
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0.00183
[3]
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KEGG Analysis of Integrated DEGs
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Functional Enrichment Analysis of Significantly Different Genes
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Table 3
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KEGG Analysis of Integrated DEGs
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[0] array · 4 items
[0]
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[1]
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[2]
P value
[3]
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hsa04512
[1]
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[3]
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hsa04024
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hsa05031
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0.004339
[3]
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hsa04020
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0.005534
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ADORA2B/P2RX1/RYR2/CASQ2/PLN
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[0]
hsa05412
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Arrhythmogenic right ventricular cardiomyopathy
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0.0059
[3]
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hsa00350
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0.01283
[3]
AOC3/MAOA
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[0]
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[1]
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0.015348
[3]
COL1A1/THBS2/TNC/MYL9
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hsa00260
[1]
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[3]
AOC3/MAOA
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gaps array · 10 items
[0]
asset:data:geo:GSE122897 not downloaded
[1]
asset:data:geo:GSE122897 licence not read
[2]
asset:data:geo:GSE15629 not downloaded
[3]
asset:data:geo:GSE15629 licence not read
[4]
asset:data:geo:GSE26969 not downloaded
[5]
asset:data:geo:GSE26969 licence not read
[6]
asset:data:geo:GSE6551 not downloaded
[7]
asset:data:geo:GSE6551 licence not read
[8]
asset:data:geo:GSE75436 not downloaded
[9]
asset:data:geo:GSE75436 licence not read
analysis object · 4 fields
state
complete
methods array · 3 items
[0] object · 10 fields
id
method-1
family
differential_expression
specific
limma_voom
label
Differential expression analysis
dsl_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
count_matrix_with_condition
evidence object · 3 fields
score
1
band
verbatim
quote
Next, the package of “limma” in R software was used to identify the DEGs.
[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
0.8
band
high
quote
GO enrichment
targets array · 0 items
gaps array · 0 items
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 · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
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: limma_voom.
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 · 5 items
[0]
GSE15629
[1]
GSE75436
[2]
GSE26969
[3]
GSE6551
[4]
GSE122897
resolved_accessions array · 5 items
[0]
GSE15629
[1]
GSE75436
[2]
GSE26969
[3]
GSE6551
[4]
GSE122897
statements array · 1 item
[0]
All datasets used and analyzed in the current research are available from the Gene Expression Omnibus GEO (http://www.ncbi.nlm.nih.gov/geo).
basis
The paper names GSE15629, GSE75436, GSE26969, GSE6551, GSE122897 in Gene Expression Omnibus GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
assets array · 5 items
[0]
source:pmid:34354366
[1]
data:geo:GSE122897
[2]
asset:table:pmid:34354366:1
[3]
asset:table:pmid:34354366:2
[4]
asset:table:pmid:34354366:3
steps array · 1 item
[0]
run_analysis
must_build object · 5 fields
dsl_operations array · 0 items
converters array · 0 items
readers array · 0 items
capabilities array · 0 items
data_gaps array · 1 item
[0]
data:geo:GSE122897
gaps array · 0 items
review object · 5 fields
state
partial
machine_critique object · 5 fields
kind
extraction_review
reader object · 5 fields
model
MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-10-31T18:33:19Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
30618
completion_tokens
1739
cached_tokens
792
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
provider
minimax
gaps array · 3 items
[0]
review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
state
absent
status
not_run
mode
null
runs array · 0 items
gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:34354366
type
paper
label
pmid:34354366
[1] object · 3 fields
id
source:pmid:34354366
type
manuscript
label
PMID 34354366 full text
[2] object · 3 fields
id
data:geo:GSE122897
type
dataset
label
GEO GSE122897
activities array · 3 items
[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
used array · 3 items
[0] object · 3 fields
id
pmid:34354366
type
paper
label
pmid:34354366
[1] object · 3 fields
id
source:pmid:34354366
type
manuscript
label
PMID 34354366 full text
[2] object · 3 fields
id
data:geo:GSE122897
type
dataset
label
GEO GSE122897
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-34354366
type
extraction
used array · 1 item
[0]
source:pmid:34354366
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE122897
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE122897
agent
agent:corpus-assay-engine
agents array · 2 items
[0] object · 3 fields
id
agent:corpus-assay-engine
type
software
label
Corpus assay engine
[1] object · 3 fields
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 object · 4 fields
parent_id
pmid:34354366
parent_hash
sha256:d2b7cfaf9c12a104b9101612a3a0bb7120fe3231612cdeb41b90c558d8100d43
fork_of
null
gaps array · 14 items
[0]
asset:data:geo:GSE122897 licence not read
[1]
asset:data:geo:GSE122897 not downloaded
[2]
asset:data:geo:GSE15629 licence not read
[3]
asset:data:geo:GSE15629 not downloaded
[4]
asset:data:geo:GSE26969 licence not read
[5]
asset:data:geo:GSE26969 not downloaded
[6]
asset:data:geo:GSE6551 licence not read
[7]
asset:data:geo:GSE6551 not downloaded
[8]
asset:data:geo:GSE75436 licence not read
[9]
asset:data:geo:GSE75436 not downloaded
[10]
execution.not_run
[11]
review.human_critique
[12]
review.independent_reader
[13]
review.machine_critique
assays array · 1 item
[0] object · 11 fields
role
analysis
definition_id
differential_expression
definition_version
f2132e96ae6c7a4e
required_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
Next, the package of “limma” in R software was used to identify the DEGs.
order_basis
analysis_only
id
assay:1
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34354366", "kind": "science-record", "revision": 8, "content_hash": "sha256:69fd4bcd79f8b1566b0a24a882bc8620072a8d6ed5490792c5b7b2f8b048449a", "created_at": "2026-11-01T15:41:47Z", "updated_at": "2026-11-01T22:47:16Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Hub Genes Associated with the Pathogenesis of Intracranial Aneurysm via Integrated Bioinformatics Analysis.", "doi": "10.2147/IJGM.S320396", "pmid": "34354366", "authors": ["Aifang Zhong", "Ning Ding", "Yang Zhou", "Guifang Yang", "Zhenyu Peng", "Hongliang Zhang", "Xiangping Chai"], "journal": "International journal of general medicine", "year": 2021, "abstract": "BACKGROUND: At present, the pathogenesis of intracranial aneurysms (IA) remains unclear, which significantly hinders the development of novel strategies for the clinical treatment. In this study, bioinformatics methods were used to identify the potential hub genes and pathways associated with the pathogenesis of IA.\nMETHODS: The gene expression datasets of patients with intracranial aneurysm were downloaded from the Gene Expression Database (GEO), and the different data sets were integrated by the robust rank aggregation (RRA) method to identify the differentially expressed genes between patients with intracranial aneurysm and the controls. The functional enrichment analyses of the significant differentially expressed genes (DEGs) were performed and the protein-protein interaction (PPI) network was constructed; thereafter, the hub genes were screened by cytoHubba plug-in of Cytoscape, and finally sequencing dataset GSE122897 was used to verify the hub genes.\nRESULTS: The GSE15629, GSE75436, GSE26969, and GSE6551 expression profiles have been included in this study, including 34 intracranial aneurysm samples and 26 control samples. The four datasets obtained 136 significant DEGs (45 up-regulated, 91 down-regulated). Enrichment analysis showed that the extracellular matrix structural constituent and the ECM-receptor interaction were closely related to the occurrence of IA. It was finally determined that eight hub genes associated with the development of IA, including VCAN, COL1A1, COL11A1, COL5A1, COL5A2, POSTN, THBS2, and CDH2.\nCONCLUSION: The discovery of potential hub genes and pathways could enhance the understanding of the molecular mechanisms associated with the development of IA. These hub genes may be potential therapeutic targets for the management and new biomarker for the diagnosis of IA.", "claims": [{"id": "claim-method", "statement": "Next, the package of “limma” in R software was used to identify the DEGs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34354366", "locator": "sections[4] \"Identification of DEGs in IA\" paragraph 2", "quote": "Next, the package of “limma” in R software was used to identify the DEGs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All datasets used and analyzed in the current research are available from the Gene Expression Omnibus GEO (http://www.ncbi.nlm.nih.gov/geo).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34354366", "locator": "sections[19] \"Data Statement and Linking\" paragraph 2", "quote": "All datasets used and analyzed in the current research are available from the Gene Expression Omnibus GEO (http://www.ncbi.nlm.nih.gov/geo)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:34354366"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE122897"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE122897"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34354366", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/IJGM.S320396", "sha256": 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(http://www.ncbi.nlm.nih.gov/geo).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All datasets used and analyzed in the current research are available from the Gene Expression Omnibus GEO (http://www.ncbi.nlm.nih.gov/geo).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3487837", "GSM3487838", "GSM3487839", "GSM3487840", "GSM3487841", "GSM3487842", "GSM3487843", "GSM3487844", "GSM3487845", "GSM3487846", "GSM3487847", "GSM3487848", "GSM3487849", "GSM3487850", "GSM3487851", "GSM3487852", "GSM3487853", "GSM3487854", "GSM3487855", "GSM3487856", "GSM3487857", "GSM3487858", "GSM3487859", "GSM3487860", "GSM3487861", "GSM3487862", "GSM3487863", "GSM3487864", "GSM3487865", "GSM3487866", "GSM3487867", "GSM3487868", "GSM3487869", "GSM3487870", "GSM3487871", "GSM3487872", "GSM3487873", "GSM3487874", "GSM3487875", "GSM3487876", "GSM3487877", "GSM3487878", "GSM3487879", "GSM3487880", "GSM3487881", 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datasets used and analyzed in the current research are available from the Gene Expression Omnibus GEO (http://www.ncbi.nlm.nih.gov/geo).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All datasets used and analyzed in the current research are available from the Gene Expression Omnibus GEO (http://www.ncbi.nlm.nih.gov/geo).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM391277", "GSM391278", "GSM391279", "GSM391280", "GSM391281", "GSM391282", "GSM391283", "GSM391284", "GSM391285", "GSM391286", "GSM391287", "GSM391288", "GSM391289", "GSM391290", "GSM391291", "GSM391292", "GSM391293", "GSM391294", "GSM391295"], "sample_count": 19, "group_sizes": null, "group_sizes_basis": null, "platform": "6244", "taxon": "Homo sapiens", "title": "Global expression profiling of ruptured and unruptured human intracranial aneurysms", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": 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