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pmid:33536775

Identification of Genes with Altered Methylation and Its Role in Early Diagnosis of Sepsis-Induced Acute Respiratory Distress Syndrome.

Jihua Feng · Jielong Pang · Dan He · Zimeng Wu · Qian Li · Pan Ji · Cuiying He · Zhimei Zhong · Hongyuan Li · Jianfeng Zhang

International journal of general medicine · 2021 doi:10.2147/IJGM.S287960

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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title
Identification of Genes with Altered Methylation and Its Role in Early Diagnosis of Sepsis-Induced Acute Respiratory Distress Syndrome.
doi
10.2147/IJGM.S287960
pmid
33536775
authors array · 10 items
[0]
Jihua Feng
[1]
Jielong Pang
[2]
Dan He
[3]
Zimeng Wu
[4]
Qian Li
[5]
Pan Ji
[6]
Cuiying He
[7]
Zhimei Zhong
[8]
Hongyuan Li
[9]
Jianfeng Zhang
journal
International journal of general medicine
year
2021
abstract
PURPOSE: Early diagnosis of sepsis-induced acute respiratory distress syndrome (ARDS) is critical for effective treatment. We aimed to identify early stage biomarkers. MATERIALS AND METHODS: Differentially expressed genes were identified in whole blood samples from patients with sepsis or ARDS based on the Gene Expression Omnibus (GEO) datasets GSE32707, GSE54514 and GSE10361. Functional enrichment analysis explored the biological characteristics of differentially expressed genes. Genes with high functional connectivity based on a protein-protein interaction network were marked as hub genes, which were validated using the GEO dataset GSE76293, and a gene set variation analysis index (GSVA) was assigned. Diagnostic and predictive ability of the hub genes were assessed by receiver operating characteristic (ROC) curve analysis. DNA methylation levels of hub genes were quantified using the GEO dataset GSE67530. RESULTS: Forty-one differentially expressed genes were shared between sepsis-specific and ARDS-specific datasets. MAP2K2 and IRF7 functional activity was highly connected in sepsis-induced ARDS. Hub genes included RETN, MVP, DEFA4, CTSG, AZU1, FMNL1, RBBP7, POLD4, RIN3, IRF7. ROC curve analysis of the hub gene GSVA index showed good diagnostic ability in sepsis or ARDS. Among genes related to sepsis-induced ARDS, 17 were differentially methylated. Principal component analysis and heatmaps indicated that gene methylation patterns differed significantly between ARDS patients and controls. CONCLUSION: We identified a genetic profile specific to early-stage sepsis-induced ARDS. The abnormal expression of these genes may be caused by hypomethylation, which may serve as a biomarker for early diagnosis of ARDS.
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sections[4] "Differentially Expressed Gene Analysis (DEG)" paragraph 2
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The limma package in R was used to screen GSE32707, GSE10361 and GSE54514 datasets to identify genes differentially expressed among sepsis, ARDS and control samples.
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sections[3] "Data Preparation" paragraph 2
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Temporal Analysis of Platelets as Cytotoxic Mediators in Sepsis-induced Acute Lung Injury (ALI)
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[87]
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[88]
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[89]
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[90]
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[91]
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[92]
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[93]
GSM1979333
sample_count
94
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Neutrophils from ARDS patients and healthy volunteers, and healthy volunteer samples treated with PI3K inhibitors
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
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gaps array · 8 items
[0]
asset:data:geo:GSE10361 not downloaded
[1]
asset:data:geo:GSE10361 licence not read
[2]
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[3]
asset:data:geo:GSE32707 licence not read
[4]
asset:data:geo:GSE54514 not downloaded
[5]
asset:data:geo:GSE54514 licence not read
[6]
asset:data:geo:GSE76293 not downloaded
[7]
asset:data:geo:GSE76293 licence not read
analysis object · 4 fields
state
partial
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id
method-1
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differential_expression
specific
limma_voom
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Differential expression analysis
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[0]
normalise_counts
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differential_expression_fit
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fdr_bh
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count_matrix_with_condition
evidence object · 3 fields
score
1
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verbatim
quote
The limma package in R was used to screen GSE32707, GSE10361 and GSE54514 datasets to identify genes differentially expressed among sepsis, ARDS and control samples.
[1] object · 10 fields
id
method-2
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principal_component_analysis
specific
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Principal component analysis
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missing_operations array · 0 items
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wide_numeric_matrix
evidence object · 3 fields
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Principal component analysis
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id
method-3
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network_analysis
specific
ppi_network
label
Network / pathway analysis
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[1]
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[2]
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evidence object · 3 fields
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0.7
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diagnostic_evaluation
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label
Diagnostic test evaluation
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[2]
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[3]
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[4]
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[5]
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reference_standard_and_test
evidence object · 3 fields
score
0.7
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medium
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ROC curve
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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
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[0]
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[1]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
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readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
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tier
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true
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normalise_counts
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differential_expression_fit
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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 · 4 items
[0]
GSE32707
[1]
GSE10361
[2]
GSE54514
[3]
GSE76293
resolved_accessions array · 4 items
[0]
GSE32707
[1]
GSE10361
[2]
GSE54514
[3]
GSE76293
statements array · 1 item
[0]
The GSE32707 gene expression profiles,19 obtained using the GPL10558 platform, contained 144 human blood samples, including 58 from patients with sepsis, 31 from patients with sepsis+ARDS, 21 from patients with systemic inflammatory response syndrome and 34 healthy controls.
basis
The paper names GSE32707, GSE10361, GSE54514, GSE76293 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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dsl_operations array · 3 items
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differential_expression_fit
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fdr_bh
assets array · 2 items
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source:pmid:33536775
[1]
data:geo:GSE10361
steps array · 1 item
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run_analysis
must_build object · 5 fields
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data:geo:GSE10361
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review object · 5 fields
state
partial
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kind
extraction_review
reader object · 5 fields
model
MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-10-31T18:26:44Z
independence
single_reader
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method
verbatim
availability
null
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3
usage object · 3 fields
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24868
completion_tokens
1710
cached_tokens
776
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[0] object · 4 fields
id
extraction
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complete
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MiniMax-M3.1-Flash
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minimax
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review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
state
absent
status
not_run
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null
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gaps array · 1 item
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execution.not_run
provenance object · 7 fields
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id
pmid:33536775
type
paper
label
pmid:33536775
[1] object · 3 fields
id
source:pmid:33536775
type
manuscript
label
PMID 33536775 full text
[2] object · 3 fields
id
data:geo:GSE10361
type
dataset
label
GEO GSE10361
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[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
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pmid:33536775
type
paper
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pmid:33536775
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id
source:pmid:33536775
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manuscript
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PMID 33536775 full text
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data:geo:GSE10361
type
dataset
label
GEO GSE10361
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agent:corpus-assay-engine
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id
activity-read-33536775
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extraction
used array · 1 item
[0]
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agent:minimax-reader
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id
activity-resolve-GSE10361
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accession_resolution
used array · 1 item
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data:geo:GSE10361
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agent:corpus-assay-engine
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agent:corpus-assay-engine
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Corpus assay engine
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agent:minimax-reader
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MiniMax literature reader
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capability_table_fingerprint
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lineage object · 4 fields
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pmid:33536775
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null
gaps array · 13 items
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asset:data:geo:GSE10361 licence not read
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[3]
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asset:data:geo:GSE54514 licence not read
[5]
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[6]
asset:data:geo:GSE76293 licence not read
[7]
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[8]
execution.not_run
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role
data_generation
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clinical_cohort
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assay_lexicon
99e1195c7d6f
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[0]
were identified in whole blood samples from patients with sepsis or ARDS based on the Gene Expression
[1]
lly expressed genes were identified in whole blood samples from patients with sepsis or ARDS based on the Ge
order_basis
paper_text_order:338
id
assay:1
[1] object · 11 fields
role
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differential_expression
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fdr_bh
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f2132e96ae6c7a4e
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The limma package in R was used to screen GSE32707, GSE10361 and GSE54514 datasets to identify genes differentially expressed among sepsis, ARDS and control samples.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33536775", "kind": "science-record", "revision": 9, "content_hash": "sha256:e540e1b8a1d778f6eb7ff59c64c987c8d49de3630936f4743d86e56861ac5252", "created_at": "2026-11-01T15:41:24Z", "updated_at": "2026-11-01T22:46:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Genes with Altered Methylation and Its Role in Early Diagnosis of Sepsis-Induced Acute Respiratory Distress Syndrome.", "doi": "10.2147/IJGM.S287960", "pmid": "33536775", "authors": ["Jihua Feng", "Jielong Pang", "Dan He", "Zimeng Wu", "Qian Li", "Pan Ji", "Cuiying He", "Zhimei Zhong", "Hongyuan Li", "Jianfeng Zhang"], "journal": "International journal of general medicine", "year": 2021, "abstract": "PURPOSE: Early diagnosis of sepsis-induced acute respiratory distress syndrome (ARDS) is critical for effective treatment. We aimed to identify early stage biomarkers.\nMATERIALS AND METHODS: Differentially expressed genes were identified in whole blood samples from patients with sepsis or ARDS based on the Gene Expression Omnibus (GEO) datasets GSE32707, GSE54514 and GSE10361. Functional enrichment analysis explored the biological characteristics of differentially expressed genes. Genes with high functional connectivity based on a protein-protein interaction network were marked as hub genes, which were validated using the GEO dataset GSE76293, and a gene set variation analysis index (GSVA) was assigned. Diagnostic and predictive ability of the hub genes were assessed by receiver operating characteristic (ROC) curve analysis. DNA methylation levels of hub genes were quantified using the GEO dataset GSE67530.\nRESULTS: Forty-one differentially expressed genes were shared between sepsis-specific and ARDS-specific datasets. MAP2K2 and IRF7 functional activity was highly connected in sepsis-induced ARDS. Hub genes included RETN, MVP, DEFA4, CTSG, AZU1, FMNL1, RBBP7, POLD4, RIN3, IRF7. ROC curve analysis of the hub gene GSVA index showed good diagnostic ability in sepsis or ARDS. Among genes related to sepsis-induced ARDS, 17 were differentially methylated. Principal component analysis and heatmaps indicated that gene methylation patterns differed significantly between ARDS patients and controls.\nCONCLUSION: We identified a genetic profile specific to early-stage sepsis-induced ARDS. The abnormal expression of these genes may be caused by hypomethylation, which may serve as a biomarker for early diagnosis of ARDS.", "claims": [{"id": "claim-method", "statement": "The limma package in R was used to screen GSE32707, GSE10361 and GSE54514 datasets to identify genes differentially expressed among sepsis, ARDS and control samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33536775", "locator": "sections[4] \"Differentially Expressed Gene Analysis (DEG)\" paragraph 2", "quote": "The limma package in R was used to screen GSE32707, GSE10361 and GSE54514 datasets to identify genes differentially expressed among sepsis, ARDS and control samples."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GSE32707 gene expression profiles,19 obtained using the GPL10558 platform, contained 144 human blood samples, including 58 from patients with sepsis, 31 from patients with sepsis+ARDS, 21 from patients with systemic inflammatory response syndrome and 34 healthy controls.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33536775", "locator": "sections[3] \"Data Preparation\" paragraph 2", "quote": "The GSE32707 gene expression profiles,19 obtained using the GPL10558 platform, contained 144 human blood samples, including 58 from patients with sepsis, 31 from patients with sepsis+ARDS, 21 from patients with systemic inflammatory response syndrome and 34 healthy controls."}], "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:33536775"], "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:GSE10361"], "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:GSE10361"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33536775", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/IJGM.S287960", "sha256": 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patients with sepsis, 31 from patients with sepsis+ARDS, 21 from patients with systemic inflammatory response syndrome and 34 healthy controls.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The GSE32707 gene expression profiles,19 obtained using the GPL10558 platform, contained 144 human blood samples, including 58 from patients with sepsis, 31 from patients with sepsis+ARDS, 21 from patients with systemic inflammatory response syndrome and 34 healthy controls.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM260537", "GSM260541", "GSM260542", "GSM261573", "GSM261575", "GSM261580", "GSM261581", "GSM261913", "GSM261914"], "sample_count": 9, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Temporal Analysis of Platelets as Cytotoxic Mediators in Sepsis-induced Acute Lung Injury (ALI)", "resolution_checked_at": "2026-11-01T15:39:54Z", 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