Corpus Engine Towards a reproducible .science file.
← All .science files

pmid:37932341

Transcriptome analysis reveals the impact of NETs activation on airway epithelial cell EMT and inflammation in bronchiolitis obliterans.

Zhongji Wu · Xiaowen Chen · Shangzhi Wu · Zhenwei Liu · Hongwei Li · Kailin Mai · Yinghui Peng · Haidi Zhang · Xiaodie Zhang · Zhaocong Zheng · Zian Fu · Dehui Chen

Scientific reports · 2023 doi:10.1038/s41598-023-45617-y

Paper

complete

Experiment

complete

Data

partial

Analysis

complete

Execution

absent

Execution evidence has not yet been added to this .science file. Explore its methods, data and open questions to plan the next step.
Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
id
pmid:37932341
kind
science-record
content_hash
sha256:65e1ac0cd5aed1275d80a74d5d0288fea10cb27d40897ac5cff9a4923ec53142
schema
https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json
created_at
2026-11-01T19:02:49Z
updated_at
2026-11-01T22:53:02Z
generator object · 2 fields
name
corpus-assay-engine
run_id
reading-sci-2026-11-01
paper object · 10 fields
state
complete
title
Transcriptome analysis reveals the impact of NETs activation on airway epithelial cell EMT and inflammation in bronchiolitis obliterans.
doi
10.1038/s41598-023-45617-y
pmid
37932341
authors array · 12 items
[0]
Zhongji Wu
[1]
Xiaowen Chen
[2]
Shangzhi Wu
[3]
Zhenwei Liu
[4]
Hongwei Li
[5]
Kailin Mai
[6]
Yinghui Peng
[7]
Haidi Zhang
[8]
Xiaodie Zhang
[9]
Zhaocong Zheng
[10]
Zian Fu
[11]
Dehui Chen
journal
Scientific reports
year
2023
abstract
Bronchiolitis obliterans (BO) is a chronic airway disease that was often indicated by the pathological presentation of narrowed and irreversible airways. However, the molecular mechanisms of BO pathogenesis remain unknown. Although neutrophil extracellular traps (NETs) can contribute to inflammatory disorders, their involvement in BO is unclear. This study aims to identify potential signaling pathways in BO by exploring the correlations between NETs and BO. GSE52761 and GSE137169 datasets were downloaded from gene expression omnibus (GEO) database. A series of bioinformatics analyses such as differential expression analysis, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and gene set enrichment analysis (GSEA) were performed on GSE52761 and GSE137169 datasets to identify BO potential signaling pathways. Two different types of BO mouse models were constructed to verify NETs involvements in BO. Additional experiments and bioinformatics analysis using human small airway epithelial cells (SAECs) were also performed to further elucidate differential genes enrichment with their respective signaling pathways in BO. Our study identified 115 differentially expressed genes (DEGs) that were found up-regulated in BO. Pathway enrichment analysis revealed that these genes were primarily involved in inflammatory signaling processes. Besides, we found that neutrophil extracellular traps (NETs) were formed and activated during BO. Our western blot analysis on lung tissue from BO mice further confirmed NETs activation in BO, where neutrophil elastase (NE) and myeloperoxidase (MPO) expression were found significantly elevated. Transcriptomic and bioinformatics analysis of NETs treated-SAECs also revealed that NETs-DEGs were primarily associated through inflammatory and epithelial-to-mesenchymal transition (EMT) -related pathways. Our study provides novel clues towards the understanding of BO pathogenesis, in which NETs contribute to BO pathogenesis through the activation of inflammatory and EMT associated pathways. The completion of our study will provide the basis for potential novel therapeutic targets in BO treatment.
claims array · 3 items
[0] object · 6 fields
id
claim-method
statement
We used the R package limma to obtain DEGs between the BO and control groups from the GSE52761 and GSE137169 datasets.
kind
methodological
target
null
evidence array · 1 item
[0] object · 3 fields
asset
source:pmid:37932341
locator
sections[8] "Data processing and differentially expressed genes identification" paragraph 2
quote
We used the R package limma to obtain DEGs between the BO and control groups from the GSE52761 and GSE137169 datasets.
state
complete
[1] object · 6 fields
id
claim-data-access
statement
Publicly available datasets were analyzed in this study. These data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52761. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137169. The raw RNA sequencing data of SAECs have been uploaded to the GEO database, and readers can access the dataset by entering a Reviewer token after the following website (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232805. Reviewer token: idgvasqibhwnzoz).
kind
methodological
target
null
evidence array · 1 item
[0] object · 3 fields
asset
source:pmid:37932341
locator
sections[37] "Data availability" paragraph 2
quote
Publicly available datasets were analyzed in this study. These data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52761. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137169. The raw RNA sequencing data of SAECs have been uploaded to the GEO database, and readers can access the dataset by entering a Reviewer token after the following website (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232805. Reviewer token: idgvasqibhwnzoz).
state
complete
[2] object · 6 fields
id
claim-target-result
statement
The study identified 115 differentially expressed genes that were found up-regulated in BO, with pathway enrichment primarily involving inflammatory signaling processes.
kind
qualitative
target
null
evidence array · 1 item
[0] object · 3 fields
asset
source:pmid:37932341
locator
sections[0] "Abstract" paragraph 1
quote
Our study identified 115 differentially expressed genes (DEGs) that were found up-regulated in BO. Pathway enrichment analysis revealed that these genes were primarily involved in inflammatory signaling processes.
state
complete
gaps array · 0 items
experiment object · 8 fields
state
complete
objective
The study identified 115 differentially expressed genes that were found up-regulated in BO, with pathway enrichment primarily involving inflammatory signaling processes.
steps array · 3 items
[0] object · 13 fields
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.
parameters object · 0 fields
inputs array · 1 item
[0]
source:pmid:37932341
outputs array · 1 item
[0]
the published estimate and its evidence
instruments array · 0 items
reagents array · 0 items
[1] object · 13 fields
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.
parameters object · 0 fields
inputs array · 1 item
[0]
data:geo:GSE137169
outputs array · 1 item
[0]
the source data with its repository provenance
instruments array · 0 items
reagents array · 0 items
[2] object · 13 fields
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.
parameters object · 0 fields
inputs array · 1 item
[0]
data:geo:GSE137169
outputs array · 1 item
[0]
the replicated result and its comparison
instruments array · 0 items
reagents array · 0 items
materials array · 0 items
instruments array · 0 items
reagents array · 0 items
conditions object · 0 fields
gaps array · 0 items
data object · 3 fields
state
partial
assets array · 4 items
[0] object · 15 fields
id
source:pmid:37932341
role
manuscript
format
xml
media_type
application/xml
uri
https://doi.org/10.1038/s41598-023-45617-y
sha256
sha256:85813081fcfcf922cf093cf71ef0042229b4209eeb3cf8c27ee7c34761a3a535
bytes
55693
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
10.1038/s41598-023-45617-y
version
null
note
Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.
structure object · 4 fields
pmcid
PMC10628238
source
europe_pmc_fulltext
coverage
whole_body
text_hash_scope
rendered_section_body
[1] object · 15 fields
id
data:geo:GSE137169
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=GSE137169
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE137169
version
null
note
Publicly available datasets were analyzed in this study. These data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52761. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137169. The raw RNA sequencing data of SAECs have been uploaded to the GEO database, and readers can access the dataset by entering a Reviewer token after the following website (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232805. Reviewer token: idgvasqibhwnzoz).
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
Publicly available datasets were analyzed in this study. These data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52761. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137169. The raw RNA sequencing data of SAECs have been uploaded to the GEO database, and readers can access the dataset by entering a Reviewer token after the following website (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232805. Reviewer token: idgvasqibhwnzoz).
access_statement_kind
data_availability_statement
sample_accessions array · 9 items
[0]
GSM4072356
[1]
GSM4072357
[2]
GSM4072358
[3]
GSM4072359
[4]
GSM4072360
[5]
GSM4072361
[6]
GSM4072362
[7]
GSM4072363
[8]
GSM4072364
sample_count
9
group_sizes
null
group_sizes_basis
null
platform
21810
taxon
Mus musculus
title
Gene analysis during the development of obliterative bronchiolitis in a murine orthotopic lung transplantation model
resolution_checked_at
2026-11-01T19:09:46Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[2] object · 15 fields
id
data:geo:GSE232805
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=GSE232805
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE232805
version
null
note
Publicly available datasets were analyzed in this study. These data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52761. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137169. The raw RNA sequencing data of SAECs have been uploaded to the GEO database, and readers can access the dataset by entering a Reviewer token after the following website (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232805. Reviewer token: idgvasqibhwnzoz).
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
Publicly available datasets were analyzed in this study. These data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52761. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137169. The raw RNA sequencing data of SAECs have been uploaded to the GEO database, and readers can access the dataset by entering a Reviewer token after the following website (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232805. Reviewer token: idgvasqibhwnzoz).
access_statement_kind
data_availability_statement
sample_accessions array · 6 items
[0]
GSM7383555
[1]
GSM7383556
[2]
GSM7383557
[3]
GSM7383558
[4]
GSM7383559
[5]
GSM7383560
sample_count
6
group_sizes
null
group_sizes_basis
null
platform
24676
taxon
Homo sapiens
title
RNA-sequencing (RNAseq) of human small airway epithelial cells treated with neutrophil extracellular traps
resolution_checked_at
2026-11-01T19:09:46Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[3] object · 15 fields
id
data:geo:GSE52761
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=GSE52761
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE52761
version
null
note
Publicly available datasets were analyzed in this study. These data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52761. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137169. The raw RNA sequencing data of SAECs have been uploaded to the GEO database, and readers can access the dataset by entering a Reviewer token after the following website (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232805. Reviewer token: idgvasqibhwnzoz).
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
Publicly available datasets were analyzed in this study. These data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52761. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137169. The raw RNA sequencing data of SAECs have been uploaded to the GEO database, and readers can access the dataset by entering a Reviewer token after the following website (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232805. Reviewer token: idgvasqibhwnzoz).
access_statement_kind
data_availability_statement
sample_accessions array · 12 items
[0]
GSM1275662
[1]
GSM1275663
[2]
GSM1275664
[3]
GSM1275665
[4]
GSM1275666
[5]
GSM1275667
[6]
GSM1275668
[7]
GSM1275669
[8]
GSM1589593
[9]
GSM1589594
[10]
GSM1589595
[11]
GSM1589596
sample_count
12
group_sizes
null
group_sizes_basis
null
platform
1355
taxon
Rattus norvegicus
title
Gene expression in 2,3-Pentanedione Induced Bronchiolitis Oblliterans
resolution_checked_at
2026-11-01T19:09:46Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 6 items
[0]
asset:data:geo:GSE137169 not downloaded
[1]
asset:data:geo:GSE137169 licence not read
[2]
asset:data:geo:GSE232805 not downloaded
[3]
asset:data:geo:GSE232805 licence not read
[4]
asset:data:geo:GSE52761 not downloaded
[5]
asset:data:geo:GSE52761 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
We used the R package limma to obtain DEGs between the BO and control groups from the GSE52761 and GSE137169 datasets.
[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
0.8
band
high
quote
PPI
[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
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 · 3 items
[0]
GSE52761
[1]
GSE137169
[2]
GSE232805
resolved_accessions array · 3 items
[0]
GSE52761
[1]
GSE137169
[2]
GSE232805
statements array · 1 item
[0]
Publicly available datasets were analyzed in this study. These data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52761. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137169. The raw RNA sequencing data of SAECs have been uploaded to the GEO database, and readers can access the dataset by entering a Reviewer token after the following website (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232805. Reviewer token: idgvasqibhwnzoz).
basis
The paper names GSE52761, GSE137169, GSE232805 in gene expression omnibus (GEO) database 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:37932341
[1]
data:geo:GSE137169
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:GSE137169
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
2026-11-01T18:58:28Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
16384
completion_tokens
1805
cached_tokens
264
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:37932341
type
paper
label
pmid:37932341
[1] object · 3 fields
id
source:pmid:37932341
type
manuscript
label
PMID 37932341 full text
[2] object · 3 fields
id
data:geo:GSE137169
type
dataset
label
GEO GSE137169
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:37932341
type
paper
label
pmid:37932341
[1] object · 3 fields
id
source:pmid:37932341
type
manuscript
label
PMID 37932341 full text
[2] object · 3 fields
id
data:geo:GSE137169
type
dataset
label
GEO GSE137169
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-37932341
type
extraction
used array · 1 item
[0]
source:pmid:37932341
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE137169
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE137169
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:37932341
parent_hash
sha256:d64704fed009546e8c74b04786ff1d54018a319368b2cf5ae481424156db7edd
fork_of
null
gaps array · 10 items
[0]
asset:data:geo:GSE137169 licence not read
[1]
asset:data:geo:GSE137169 not downloaded
[2]
asset:data:geo:GSE232805 licence not read
[3]
asset:data:geo:GSE232805 not downloaded
[4]
asset:data:geo:GSE52761 licence not read
[5]
asset:data:geo:GSE52761 not downloaded
[6]
execution.not_run
[7]
review.human_critique
[8]
review.independent_reader
[9]
review.machine_critique
assays array · 4 items
[0] object · 11 fields
role
data_generation
definition_id
animal_model
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.69
evidence array · 1 item
[0]
ignaling pathways. Two different types of BO mouse models were constructed to verify NETs invol
order_basis
paper_text_order:954
id
assay:1
[1] object · 11 fields
role
data_generation
definition_id
western_blot
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.93
evidence array · 1 item
[0]
Ts) were formed and activated during BO. Our western blot analysis on lung tissue from BO mice further
order_basis
paper_text_order:1555
id
assay:2
[2] 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
0.93
evidence array · 1 item
[0]
rentially expressed genes identification Raw microarray data for the BO datasets were downloaded fro
order_basis
paper_text_order:2855
id
assay:3
[3] 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]
We used the R package limma to obtain DEGs between the BO and control groups from the GSE52761 and GSE137169 datasets.
order_basis
consumes_earlier_output
id
assay:4
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37932341", "kind": "science-record", "revision": 5, "content_hash": "sha256:65e1ac0cd5aed1275d80a74d5d0288fea10cb27d40897ac5cff9a4923ec53142", "created_at": "2026-11-01T19:02:49Z", "updated_at": "2026-11-01T22:53:02Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Transcriptome analysis reveals the impact of NETs activation on airway epithelial cell EMT and inflammation in bronchiolitis obliterans.", "doi": "10.1038/s41598-023-45617-y", "pmid": "37932341", "authors": ["Zhongji Wu", "Xiaowen Chen", "Shangzhi Wu", "Zhenwei Liu", "Hongwei Li", "Kailin Mai", "Yinghui Peng", "Haidi Zhang", "Xiaodie Zhang", "Zhaocong Zheng", "Zian Fu", "Dehui Chen"], "journal": "Scientific reports", "year": 2023, "abstract": "Bronchiolitis obliterans (BO) is a chronic airway disease that was often indicated by the pathological presentation of narrowed and irreversible airways. However, the molecular mechanisms of BO pathogenesis remain unknown. Although neutrophil extracellular traps (NETs) can contribute to inflammatory disorders, their involvement in BO is unclear. This study aims to identify potential signaling pathways in BO by exploring the correlations between NETs and BO. GSE52761 and GSE137169 datasets were downloaded from gene expression omnibus (GEO) database. A series of bioinformatics analyses such as differential expression analysis, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and gene set enrichment analysis (GSEA) were performed on GSE52761 and GSE137169 datasets to identify BO potential signaling pathways. Two different types of BO mouse models were constructed to verify NETs involvements in BO. Additional experiments and bioinformatics analysis using human small airway epithelial cells (SAECs) were also performed to further elucidate differential genes enrichment with their respective signaling pathways in BO. Our study identified 115 differentially expressed genes (DEGs) that were found up-regulated in BO. Pathway enrichment analysis revealed that these genes were primarily involved in inflammatory signaling processes. Besides, we found that neutrophil extracellular traps (NETs) were formed and activated during BO. Our western blot analysis on lung tissue from BO mice further confirmed NETs activation in BO, where neutrophil elastase (NE) and myeloperoxidase (MPO) expression were found significantly elevated. Transcriptomic and bioinformatics analysis of NETs treated-SAECs also revealed that NETs-DEGs were primarily associated through inflammatory and epithelial-to-mesenchymal transition (EMT) -related pathways. Our study provides novel clues towards the understanding of BO pathogenesis, in which NETs contribute to BO pathogenesis through the activation of inflammatory and EMT associated pathways. The completion of our study will provide the basis for potential novel therapeutic targets in BO treatment.", "claims": [{"id": "claim-method", "statement": "We used the R package limma to obtain DEGs between the BO and control groups from the GSE52761 and GSE137169 datasets.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37932341", "locator": "sections[8] \"Data processing and differentially expressed genes identification\" paragraph 2", "quote": "We used the R package limma to obtain DEGs between the BO and control groups from the GSE52761 and GSE137169 datasets."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. These data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52761. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137169. The raw RNA sequencing data of SAECs have been uploaded to the GEO database, and readers can access the dataset by entering a Reviewer token after the following website (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232805. Reviewer token: idgvasqibhwnzoz).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37932341", "locator": "sections[37] \"Data availability\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. These data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52761. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137169. The raw RNA sequencing data of SAECs have been uploaded to the GEO database, and readers can access the dataset by entering a Reviewer token after the following website (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232805. Reviewer token: idgvasqibhwnzoz)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified 115 differentially expressed genes that were found up-regulated in BO, with pathway enrichment primarily involving inflammatory signaling processes.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37932341", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Our study identified 115 differentially expressed genes (DEGs) that were found up-regulated in BO. Pathway enrichment analysis revealed that these genes were primarily involved in inflammatory signaling processes."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified 115 differentially expressed genes that were found up-regulated in BO, with pathway enrichment primarily involving inflammatory signaling processes.", "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:37932341"], "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:GSE137169"], "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:GSE137169"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37932341", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1038/s41598-023-45617-y", "sha256": "sha256:85813081fcfcf922cf093cf71ef0042229b4209eeb3cf8c27ee7c34761a3a535", "bytes": 55693, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1038/s41598-023-45617-y", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10628238", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE137169", "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=GSE137169", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE137169", "version": null, "note": "Publicly available datasets were analyzed in this study. These data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52761. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137169. The raw RNA sequencing data of SAECs have been uploaded to the GEO database, and readers can access the dataset by entering a Reviewer token after the following website (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232805. Reviewer token: idgvasqibhwnzoz).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. These data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52761. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137169. The raw RNA sequencing data of SAECs have been uploaded to the GEO database, and readers can access the dataset by entering a Reviewer token after the following website (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232805. Reviewer token: idgvasqibhwnzoz).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4072356", "GSM4072357", "GSM4072358", "GSM4072359", "GSM4072360", "GSM4072361", "GSM4072362", "GSM4072363", "GSM4072364"], "sample_count": 9, "group_sizes": null, "group_sizes_basis": null, "platform": "21810", "taxon": "Mus musculus", "title": "Gene analysis during the development of obliterative bronchiolitis in a murine orthotopic lung transplantation model", "resolution_checked_at": "2026-11-01T19:09:46Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE232805", "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=GSE232805", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE232805", "version": null, "note": "Publicly available datasets were analyzed in this study. These data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52761. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137169. The raw RNA sequencing data of SAECs have been uploaded to the GEO database, and readers can access the dataset by entering a Reviewer token after the following website (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232805. Reviewer token: idgvasqibhwnzoz).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. These data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52761. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137169. The raw RNA sequencing data of SAECs have been uploaded to the GEO database, and readers can access the dataset by entering a Reviewer token after the following website (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232805. Reviewer token: idgvasqibhwnzoz).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM7383555", "GSM7383556", "GSM7383557", "GSM7383558", "GSM7383559", "GSM7383560"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "24676", "taxon": "Homo sapiens", "title": "RNA-sequencing (RNAseq) of human small airway epithelial cells treated with neutrophil extracellular traps", "resolution_checked_at": "2026-11-01T19:09:46Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE52761", "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=GSE52761", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE52761", "version": null, "note": "Publicly available datasets were analyzed in this study. These data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52761. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137169. The raw RNA sequencing data of SAECs have been uploaded to the GEO database, and readers can access the dataset by entering a Reviewer token after the following website (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232805. Reviewer token: idgvasqibhwnzoz).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. These data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52761. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137169. The raw RNA sequencing data of SAECs have been uploaded to the GEO database, and readers can access the dataset by entering a Reviewer token after the following website (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232805. Reviewer token: idgvasqibhwnzoz).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1275662", "GSM1275663", "GSM1275664", "GSM1275665", "GSM1275666", "GSM1275667", "GSM1275668", "GSM1275669", "GSM1589593", "GSM1589594", "GSM1589595", "GSM1589596"], "sample_count": 12, "group_sizes": null, "group_sizes_basis": null, "platform": "1355", "taxon": "Rattus norvegicus", "title": "Gene expression in 2,3-Pentanedione Induced Bronchiolitis Oblliterans", "resolution_checked_at": "2026-11-01T19:09:46Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE137169 not downloaded", "asset:data:geo:GSE137169 licence not read", "asset:data:geo:GSE232805 not downloaded", "asset:data:geo:GSE232805 licence not read", "asset:data:geo:GSE52761 not downloaded", "asset:data:geo:GSE52761 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "We used the R package limma to obtain DEGs between the BO and control groups from the GSE52761 and GSE137169 datasets."}}, {"id": "method-2", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "PPI"}}, {"id": "method-3", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "Pathway enrichment"}}], "targets": [], "gaps": []}, "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": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "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": ["GSE52761", "GSE137169", "GSE232805"], "resolved_accessions": ["GSE52761", "GSE137169", "GSE232805"], "statements": ["Publicly available datasets were analyzed in this study. These data can be found here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE52761. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE137169. The raw RNA sequencing data of SAECs have been uploaded to the GEO database, and readers can access the dataset by entering a Reviewer token after the following website (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE232805. Reviewer token: idgvasqibhwnzoz)."], "basis": "The paper names GSE52761, GSE137169, GSE232805 in gene expression omnibus (GEO) database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:37932341", "data:geo:GSE137169"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE137169"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:58:28Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 16384, "completion_tokens": 1805, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:37932341", "type": "paper", "label": "pmid:37932341"}, {"id": "source:pmid:37932341", "type": "manuscript", "label": "PMID 37932341 full text"}, {"id": "data:geo:GSE137169", "type": "dataset", "label": "GEO GSE137169"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37932341", "type": "paper", "label": "pmid:37932341"}, {"id": "source:pmid:37932341", "type": "manuscript", "label": "PMID 37932341 full text"}, {"id": "data:geo:GSE137169", "type": "dataset", "label": "GEO GSE137169"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37932341", "type": "extraction", "used": ["source:pmid:37932341"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE137169", "type": "accession_resolution", "used": ["data:geo:GSE137169"], "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:37932341", "parent_hash": "sha256:d64704fed009546e8c74b04786ff1d54018a319368b2cf5ae481424156db7edd", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE137169 licence not read", "asset:data:geo:GSE137169 not downloaded", "asset:data:geo:GSE232805 licence not read", "asset:data:geo:GSE232805 not downloaded", "asset:data:geo:GSE52761 licence not read", "asset:data:geo:GSE52761 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["ignaling pathways. Two different types of BO mouse models were constructed to verify NETs invol"], "order_basis": "paper_text_order:954", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["Ts) were formed and activated during BO. Our western blot analysis on lung tissue from BO mice further"], "order_basis": "paper_text_order:1555", "id": "assay:2"}, {"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": ["rentially expressed genes identification Raw microarray data for the BO datasets were downloaded fro"], "order_basis": "paper_text_order:2855", "id": "assay:3"}, {"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": ["We used the R package limma to obtain DEGs between the BO and control groups from the GSE52761 and GSE137169 datasets."], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}