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pmid:35433978

Seven ferroptosis-specific expressed genes are considered as potential biomarkers for the diagnosis and treatment of cigarette smoke-induced chronic obstructive pulmonary disease.

Zhiwei Lin · Yifan Xu · Lili Guan · Lijie Qin · Jiabin Ding · Qingling Zhang · Luqian Zhou

Annals of translational medicine · 2022 doi:10.21037/atm-22-1009

Paper

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Experiment

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title
Seven ferroptosis-specific expressed genes are considered as potential biomarkers for the diagnosis and treatment of cigarette smoke-induced chronic obstructive pulmonary disease.
doi
10.21037/atm-22-1009
pmid
35433978
authors array · 7 items
[0]
Zhiwei Lin
[1]
Yifan Xu
[2]
Lili Guan
[3]
Lijie Qin
[4]
Jiabin Ding
[5]
Qingling Zhang
[6]
Luqian Zhou
journal
Annals of translational medicine
year
2022
abstract
Background: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease characterized by incomplete reversible airway obstruction, with high mortality and disability rates, and smoking is the primary risk factor for COPD. Studies performed to date have confirmed that iron and ferroptosis play crucial roles in the development of cigarette smoke-induced COPD, but the exact mechanisms have not been fully elucidated. Methods: The microarray datasets GSE10006, GSE11784, and GSE20257 were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) between COPD smokers and non-smokers airway epithelial. Protein-protein interaction (PPI) and hub gene networks were constructed using the STRING database and Cytoscape software. At the same time, the 3 datasets were screened for ferroptosis-related genes that were co-differentially expressed. The ferroptosis-related hub genes (FRHGs) that overlapped with the ferroptosis-related genes and hub genes were then identified. Next, the mRNA-miRNA network was constructed, and Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for target genes were performed. Finally, GSE19407, GSE994, and GSE27973 were used to evaluate the expression of hub genes. Results: We identified 7 potential FRHGs (NQO1, AKR1C3, AKR1C1, GPX2, TXNRD1, SRXN1, SLC7A11), which showed good diagnostic properties. The molecular functions (MFs) of FRHGs mainly influence biological processes (BPs) responding to oxidative stress. Nrf2 pathways may be the key pathways regulating ferroptosis in cigarette smoke-induced COPD. Meanwhile, co-expressed mRNAs and miRNAs were selected to construct mRNA-miRNA interaction networks. Furthermore, based on the 7 FRHGs mentioned above, we found that benzoic acid showed high drug targeting relevance. Conclusions: This work identified 7 FRHGs as potential biomarkers for the diagnosis and treatment of COPD and provided insights into the mechanisms of disease development in cigarette smoke-induced COPD at the transcriptome level.
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Genes with an adjusted P value less than 0.05 and absolute fold change (FC) greater than 1 were considered as DEGs using the ‘limma’ package of R software (22). Receiver operating characteristic (ROC) curve analysis was performed using HiPlot software (version 0.1.0) to determine the sensitivity and specificity of target genes.
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sections[4] "Analysis of differential gene expression" paragraph 3
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Genes with an adjusted P value less than 0.05 and absolute fold change (FC) greater than 1 were considered as DEGs using the ‘limma’ package of R software (22).
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sections[9] "Validation of ferroptosis hub genes" paragraph 2
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Receiver operating characteristic (ROC) curve analysis was performed using HiPlot software (version 0.1.0) to determine the sensitivity and specificity of target genes.
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The mRNA expression profile datasets GSE10006, GSE11784, GSE20257, GSE19407, GSE994, and GSE27973 were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) in the data format MINiML.
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sections[3] "Data acquisition" paragraph 2
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The mRNA expression profile datasets GSE10006, GSE11784, GSE20257, GSE19407, GSE994, and GSE27973 were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) in the data format MINiML.
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We identified 7 potential FRHGs (NQO1, AKR1C3, AKR1C1, GPX2, TXNRD1, SRXN1, SLC7A11), which showed good diagnostic properties.
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sections[0] "Abstract" paragraph 3
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We identified 7 potential FRHGs (NQO1, AKR1C3, AKR1C1, GPX2, TXNRD1, SRXN1, SLC7A11), which showed good diagnostic properties.
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We identified 7 potential FRHGs (NQO1, AKR1C3, AKR1C1, GPX2, TXNRD1, SRXN1, SLC7A11), which showed good diagnostic properties.
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Decreased Expression of Intelectin 1 in The Human Airway Epithelium of Smokers Compared to Nonsmokers
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GSM434054
[117]
GSM434055
[118]
GSM434056
[119]
GSM434057
[120]
GSM434058
[121]
GSM434059
[122]
GSM434060
[123]
GSM434061
[124]
GSM434062
[125]
GSM434063
[126]
GSM434064
sample_count
127
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Smoking-induced Wnt pathway downregulation
resolution_checked_at
2026-11-01T18:06:43Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[4] object · 15 fields
id
data:geo:GSE20257
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=GSE20257
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE20257
version
null
note
The mRNA expression profile datasets GSE10006, GSE11784, GSE20257, GSE19407, GSE994, and GSE27973 were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) in the data format MINiML.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The mRNA expression profile datasets GSE10006, GSE11784, GSE20257, GSE19407, GSE994, and GSE27973 were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) in the data format MINiML.
access_statement_kind
repository_route_statement
sample_accessions array · 135 items
[0]
GSM101095
[1]
GSM101096
[2]
GSM101097
[3]
GSM101098
[4]
GSM101100
[5]
GSM101101
[6]
GSM101102
[7]
GSM101103
[8]
GSM101104
[9]
GSM101105
[10]
GSM101106
[11]
GSM101107
[12]
GSM101111
[13]
GSM101113
[14]
GSM101114
[15]
GSM101115
[16]
GSM101116
[17]
GSM114089
[18]
GSM114090
[19]
GSM190149
[20]
GSM190150
[21]
GSM190151
[22]
GSM190152
[23]
GSM190153
[24]
GSM190154
[25]
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[26]
GSM190156
[27]
GSM252828
[28]
GSM252829
[29]
GSM252830
[30]
GSM252831
[31]
GSM252833
[32]
GSM252835
[33]
GSM252836
[34]
GSM252837
[35]
GSM252838
[36]
GSM252839
[37]
GSM252841
[38]
GSM252871
[39]
GSM252876
[40]
GSM252879
[41]
GSM252880
[42]
GSM252881
[43]
GSM252882
[44]
GSM252884
[45]
GSM252885
[46]
GSM254149
[47]
GSM254150
[48]
GSM254151
[49]
GSM254152
[50]
GSM254157
[51]
GSM254158
[52]
GSM254159
[53]
GSM254160
[54]
GSM254161
[55]
GSM254163
[56]
GSM254169
[57]
GSM254172
[58]
GSM254173
[59]
GSM254174
[60]
GSM254175
[61]
GSM254176
[62]
GSM298219
[63]
GSM298220
[64]
GSM298221
[65]
GSM298222
[66]
GSM298223
[67]
GSM298224
[68]
GSM298225
[69]
GSM298226
[70]
GSM298227
[71]
GSM298228
[72]
GSM298229
[73]
GSM298230
[74]
GSM298231
[75]
GSM298232
[76]
GSM298233
[77]
GSM298234
[78]
GSM298235
[79]
GSM298236
[80]
GSM298237
[81]
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[82]
GSM298239
[83]
GSM298240
[84]
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[85]
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[86]
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[87]
GSM298244
[88]
GSM298245
[89]
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[90]
GSM298247
[91]
GSM300859
[92]
GSM302396
[93]
GSM302397
[94]
GSM302399
[95]
GSM350871
[96]
GSM350873
[97]
GSM350874
[98]
GSM350955
[99]
GSM350956
[100]
GSM350957
[101]
GSM350958
[102]
GSM364037
[103]
GSM364038
[104]
GSM364041
[105]
GSM364045
[106]
GSM364046
[107]
GSM364048
[108]
GSM410161
[109]
GSM410162
[110]
GSM410163
[111]
GSM410164
[112]
GSM410165
[113]
GSM434049
[114]
GSM434050
[115]
GSM434051
[116]
GSM434052
[117]
GSM434053
[118]
GSM434054
[119]
GSM434055
[120]
GSM434056
[121]
GSM434057
[122]
GSM434058
[123]
GSM434059
[124]
GSM434060
[125]
GSM434061
[126]
GSM434062
[127]
GSM434063
[128]
GSM434064
[129]
GSM458579
[130]
GSM458580
[131]
GSM458581
[132]
GSM458582
[133]
GSM469991
[134]
GSM470000
sample_count
135
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Smoking-induced Disarray of the Apical Junctional Complex Gene Expression Architecture in the Human Airway Epithelium
resolution_checked_at
2026-11-01T18:06:43Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[5] object · 15 fields
id
data:geo:GSE27973
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=GSE27973
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE27973
version
null
note
The mRNA expression profile datasets GSE10006, GSE11784, GSE20257, GSE19407, GSE994, and GSE27973 were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) in the data format MINiML.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The mRNA expression profile datasets GSE10006, GSE11784, GSE20257, GSE19407, GSE994, and GSE27973 were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) in the data format MINiML.
access_statement_kind
repository_route_statement
sample_accessions array · 16 items
[0]
GSM692115
[1]
GSM692116
[2]
GSM692117
[3]
GSM692118
[4]
GSM692119
[5]
GSM692120
[6]
GSM692121
[7]
GSM692122
[8]
GSM692123
[9]
GSM692124
[10]
GSM692125
[11]
GSM692126
[12]
GSM692127
[13]
GSM692128
[14]
GSM692129
[15]
GSM692130
sample_count
16
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Human airway epithelial responses to rhinovirus infection and cigarette smoke extract alone and in combination
resolution_checked_at
2026-11-01T18:06:43Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[6] object · 15 fields
id
data:geo:GSE994
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=GSE994
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE994
version
null
note
The mRNA expression profile datasets GSE10006, GSE11784, GSE20257, GSE19407, GSE994, and GSE27973 were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) in the data format MINiML.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The mRNA expression profile datasets GSE10006, GSE11784, GSE20257, GSE19407, GSE994, and GSE27973 were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) in the data format MINiML.
access_statement_kind
repository_route_statement
sample_accessions array · 75 items
[0]
GSM15684
[1]
GSM15685
[2]
GSM15686
[3]
GSM15687
[4]
GSM15688
[5]
GSM15689
[6]
GSM15690
[7]
GSM15691
[8]
GSM15692
[9]
GSM15693
[10]
GSM15694
[11]
GSM15695
[12]
GSM15696
[13]
GSM15697
[14]
GSM15698
[15]
GSM15699
[16]
GSM15700
[17]
GSM15701
[18]
GSM15702
[19]
GSM15703
[20]
GSM15704
[21]
GSM15705
[22]
GSM15706
[23]
GSM15707
[24]
GSM15708
[25]
GSM15709
[26]
GSM15710
[27]
GSM15711
[28]
GSM15712
[29]
GSM15713
[30]
GSM15714
[31]
GSM15715
[32]
GSM15716
[33]
GSM15717
[34]
GSM15718
[35]
GSM15719
[36]
GSM15720
[37]
GSM15721
[38]
GSM15722
[39]
GSM15723
[40]
GSM15724
[41]
GSM15725
[42]
GSM15726
[43]
GSM15727
[44]
GSM15728
[45]
GSM15729
[46]
GSM15730
[47]
GSM15731
[48]
GSM15732
[49]
GSM15733
[50]
GSM15734
[51]
GSM15735
[52]
GSM15736
[53]
GSM15737
[54]
GSM15738
[55]
GSM15739
[56]
GSM15740
[57]
GSM15741
[58]
GSM15742
[59]
GSM15743
[60]
GSM15744
[61]
GSM15745
[62]
GSM15746
[63]
GSM15747
[64]
GSM15748
[65]
GSM15749
[66]
GSM15750
[67]
GSM15751
[68]
GSM15752
[69]
GSM15753
[70]
GSM15754
[71]
GSM15755
[72]
GSM15756
[73]
GSM15757
[74]
GSM15758
sample_count
75
group_sizes
null
group_sizes_basis
null
platform
96
taxon
Homo sapiens
title
Effects of cigarette smoke on the human airway epithelial cell transcriptome
resolution_checked_at
2026-11-01T17:30:42Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 12 items
[0]
asset:data:geo:GSE10006 not downloaded
[1]
asset:data:geo:GSE10006 licence not read
[2]
asset:data:geo:GSE11784 not downloaded
[3]
asset:data:geo:GSE11784 licence not read
[4]
asset:data:geo:GSE19407 not downloaded
[5]
asset:data:geo:GSE19407 licence not read
[6]
asset:data:geo:GSE20257 not downloaded
[7]
asset:data:geo:GSE20257 licence not read
[8]
asset:data:geo:GSE27973 not downloaded
[9]
asset:data:geo:GSE27973 licence not read
[10]
asset:data:geo:GSE994 not downloaded
[11]
asset:data:geo:GSE994 licence not read
analysis object · 4 fields
state
partial
methods array · 4 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
reordered
quote
Genes with an adjusted P value less than 0.05 and absolute fold change (FC) greater than 1 were considered as DEGs using the ‘limma’ package of R software (22). Receiver operating characteristic (ROC) curve analysis was performed using HiPlot software (version 0.1.0) to determine the sensitivity and specificity of target genes.
[1] object · 10 fields
id
method-2
family
principal_component_analysis
specific
pca
label
Principal component analysis
dsl_operations array · 1 item
[0]
pca_fit
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
wide_numeric_matrix
evidence object · 3 fields
score
0.8
band
high
quote
principal component analysis
[2] object · 10 fields
id
method-3
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
[3] object · 10 fields
id
method-4
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
targets array · 0 items
gaps array · 1 item
[0]
method.reader_differs_from_extractor
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 · 6 items
[0]
GSE10006
[1]
GSE11784
[2]
GSE20257
[3]
GSE19407
[4]
GSE994
[5]
GSE27973
resolved_accessions array · 6 items
[0]
GSE10006
[1]
GSE11784
[2]
GSE20257
[3]
GSE19407
[4]
GSE994
[5]
GSE27973
statements array · 1 item
[0]
The mRNA expression profile datasets GSE10006, GSE11784, GSE20257, GSE19407, GSE994, and GSE27973 were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) in the data format MINiML.
basis
The paper names GSE10006, GSE11784, GSE20257, GSE19407, GSE994, GSE27973 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 · 2 items
[0]
source:pmid:35433978
[1]
data:geo:GSE10006
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:GSE10006
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
2026-11-01T17:42:55Z
independence
single_reader
evidence_check object · 2 fields
method
reordered
availability
null
calls
5
usage object · 3 fields
prompt_tokens
10823
completion_tokens
2010
cached_tokens
128
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:35433978
type
paper
label
pmid:35433978
[1] object · 3 fields
id
source:pmid:35433978
type
manuscript
label
PMID 35433978 full text
[2] object · 3 fields
id
data:geo:GSE10006
type
dataset
label
GEO GSE10006
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:35433978
type
paper
label
pmid:35433978
[1] object · 3 fields
id
source:pmid:35433978
type
manuscript
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PMID 35433978 full text
[2] object · 3 fields
id
data:geo:GSE10006
type
dataset
label
GEO GSE10006
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-35433978
type
extraction
used array · 1 item
[0]
source:pmid:35433978
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE10006
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE10006
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:35433978
parent_hash
sha256:006b20b367d38dba7637dbbd544813b86b42fb8b56ee54637fe1d9fc1563f62b
fork_of
null
gaps array · 17 items
[0]
asset:data:geo:GSE10006 licence not read
[1]
asset:data:geo:GSE10006 not downloaded
[2]
asset:data:geo:GSE11784 licence not read
[3]
asset:data:geo:GSE11784 not downloaded
[4]
asset:data:geo:GSE19407 licence not read
[5]
asset:data:geo:GSE19407 not downloaded
[6]
asset:data:geo:GSE20257 licence not read
[7]
asset:data:geo:GSE20257 not downloaded
[8]
asset:data:geo:GSE27973 licence not read
[9]
asset:data:geo:GSE27973 not downloaded
[10]
asset:data:geo:GSE994 licence not read
[11]
asset:data:geo:GSE994 not downloaded
[12]
execution.not_run
[13]
method.reader_differs_from_extractor
[14]
review.human_critique
[15]
review.independent_reader
[16]
review.machine_critique
assays array · 2 items
[0] object · 11 fields
role
data_generation
definition_id
microarray
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.99
evidence array · 2 items
[0]
have not been fully elucidated. Methods: The microarray datasets GSE10006, GSE11784, and GSE20257 we
[1]
sion The normalized expression matrix of the microarray data was downloaded from the 4 datasets and
order_basis
paper_text_order:583
id
assay:1
[1] 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]
Genes with an adjusted P value less than 0.05 and absolute fold change (FC) greater than 1 were considered as DEGs using the ‘limma’ package of R software (22). Receiver operating characteristic (ROC) curve analysis was performed using HiPlot software (version 0.1.0) to determine the sensitivity and specificity of target genes.
order_basis
consumes_earlier_output
id
assay:2
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35433978", "kind": "science-record", "revision": 5, "content_hash": "sha256:c63b068d244aa76b55417ad484cc3c85cbece5802953786b5d67ea0823889745", "created_at": "2026-11-01T18:14:17Z", "updated_at": "2026-11-01T22:48:52Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Seven ferroptosis-specific expressed genes are considered as potential biomarkers for the diagnosis and treatment of cigarette smoke-induced chronic obstructive pulmonary disease.", "doi": "10.21037/atm-22-1009", "pmid": "35433978", "authors": ["Zhiwei Lin", "Yifan Xu", "Lili Guan", "Lijie Qin", "Jiabin Ding", "Qingling Zhang", "Luqian Zhou"], "journal": "Annals of translational medicine", "year": 2022, "abstract": "Background: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease characterized by incomplete reversible airway obstruction, with high mortality and disability rates, and smoking is the primary risk factor for COPD. Studies performed to date have confirmed that iron and ferroptosis play crucial roles in the development of cigarette smoke-induced COPD, but the exact mechanisms have not been fully elucidated.\nMethods: The microarray datasets GSE10006, GSE11784, and GSE20257 were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs) between COPD smokers and non-smokers airway epithelial. Protein-protein interaction (PPI) and hub gene networks were constructed using the STRING database and Cytoscape software. At the same time, the 3 datasets were screened for ferroptosis-related genes that were co-differentially expressed. The ferroptosis-related hub genes (FRHGs) that overlapped with the ferroptosis-related genes and hub genes were then identified. Next, the mRNA-miRNA network was constructed, and Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for target genes were performed. Finally, GSE19407, GSE994, and GSE27973 were used to evaluate the expression of hub genes.\nResults: We identified 7 potential FRHGs (NQO1, AKR1C3, AKR1C1, GPX2, TXNRD1, SRXN1, SLC7A11), which showed good diagnostic properties. The molecular functions (MFs) of FRHGs mainly influence biological processes (BPs) responding to oxidative stress. Nrf2 pathways may be the key pathways regulating ferroptosis in cigarette smoke-induced COPD. Meanwhile, co-expressed mRNAs and miRNAs were selected to construct mRNA-miRNA interaction networks. Furthermore, based on the 7 FRHGs mentioned above, we found that benzoic acid showed high drug targeting relevance.\nConclusions: This work identified 7 FRHGs as potential biomarkers for the diagnosis and treatment of COPD and provided insights into the mechanisms of disease development in cigarette smoke-induced COPD at the transcriptome level.", "claims": [{"id": "claim-method", "statement": "Genes with an adjusted P value less than 0.05 and absolute fold change (FC) greater than 1 were considered as DEGs using the ‘limma’ package of R software (22). Receiver operating characteristic (ROC) curve analysis was performed using HiPlot software (version 0.1.0) to determine the sensitivity and specificity of target genes.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35433978", "locator": "sections[4] \"Analysis of differential gene expression\" paragraph 3", "quote": "Genes with an adjusted P value less than 0.05 and absolute fold change (FC) greater than 1 were considered as DEGs using the ‘limma’ package of R software (22)."}, {"asset": "source:pmid:35433978", "locator": "sections[9] \"Validation of ferroptosis hub genes\" paragraph 2", "quote": "Receiver operating characteristic (ROC) curve analysis was performed using HiPlot software (version 0.1.0) to determine the sensitivity and specificity of target genes."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mRNA expression profile datasets GSE10006, GSE11784, GSE20257, GSE19407, GSE994, and GSE27973 were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) in the data format MINiML.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35433978", "locator": "sections[3] \"Data acquisition\" paragraph 2", "quote": "The mRNA expression profile datasets GSE10006, GSE11784, GSE20257, GSE19407, GSE994, and GSE27973 were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) in the data format MINiML."}], "state": "complete"}, {"id": "claim-target-result", "statement": "We identified 7 potential FRHGs (NQO1, AKR1C3, AKR1C1, GPX2, TXNRD1, SRXN1, SLC7A11), which showed good diagnostic properties.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35433978", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We identified 7 potential FRHGs (NQO1, AKR1C3, AKR1C1, GPX2, TXNRD1, SRXN1, SLC7A11), which showed good diagnostic properties."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "We identified 7 potential FRHGs (NQO1, AKR1C3, AKR1C1, GPX2, TXNRD1, SRXN1, SLC7A11), which showed good diagnostic properties.", "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:35433978"], "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:GSE10006"], "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:GSE10006"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35433978", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/atm-22-1009", "sha256": 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GSE994, and GSE27973 were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) in the data format MINiML.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The mRNA expression profile datasets GSE10006, GSE11784, GSE20257, GSE19407, GSE994, and GSE27973 were downloaded from the GEO database (https://www.ncbi.nlm.nih.gov/geo/) in the data format MINiML.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM101095", "GSM101096", "GSM101097", "GSM101098", "GSM101100", "GSM101101", "GSM101102", "GSM101103", "GSM101104", "GSM101105", "GSM101106", "GSM101107", "GSM101111", "GSM101113", "GSM101114", "GSM101115", "GSM101116", "GSM114089", "GSM114090", "GSM190149", "GSM190150", "GSM190151", "GSM190152", "GSM190153", "GSM190154", "GSM190155", "GSM190156", "GSM252828", "GSM252829", "GSM252830", "GSM252831", "GSM252833", "GSM252835", "GSM252836", "GSM252837", "GSM252838", "GSM252839", "GSM252841", 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Methods: The microarray datasets GSE10006, GSE11784, and GSE20257 we", "sion The normalized expression matrix of the microarray data was downloaded from the 4 datasets and"], "order_basis": "paper_text_order:583", "id": "assay:1"}, {"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Genes with an adjusted P value less than 0.05 and absolute fold change (FC) greater than 1 were considered as DEGs using the ‘limma’ package of R software (22). Receiver operating characteristic (ROC) curve analysis was performed using HiPlot software (version 0.1.0) to determine the sensitivity and specificity of target genes."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}