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pmid:37124627

Unveiling DNA damage repair-based molecular subtypes, tumor microenvironment and pharmacogenomic landscape in gastric cancer.

Weiqi Kong · Zhiqiang Wang · Bingyi Wang

Frontiers in genetics · 2023 doi:10.3389/fgene.2023.1118889

Paper

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Experiment

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title
Unveiling DNA damage repair-based molecular subtypes, tumor microenvironment and pharmacogenomic landscape in gastric cancer.
doi
10.3389/fgene.2023.1118889
pmid
37124627
authors array · 3 items
[0]
Weiqi Kong
[1]
Zhiqiang Wang
[2]
Bingyi Wang
journal
Frontiers in genetics
year
2023
abstract
Objective: The current molecular classification system for gastric cancer covers genomic, molecular, and morphological characteristics. Non-etheless, classification of gastric cancer based upon DNA damage repair is still lacking. Here, we defined DNA damage repair-based subtypes across gastric cancer and identified clinicopathological, tumor microenvironment and pharmacogenomic features. Methods: Unsupervised clustering analysis was executed in the TCGA-STAD cohort based upon the transcriptional expression profiling of DNA damage repair genes. LASSO computational approach was adopted for generating a DNA damage repair-relevant gene signature. The identified subtypes or signature were externally verified in the GSE84426 or GSE84433 cohort. The transcriptional levels of immunomodulators, abundance of immune cells and somatic mutations were measured, respectively. Immunotherapeutic response, and drug sensitivity were investigated. The DNA damage repair-relevant genes were further experimentally verified. Results: Two DNA damage repair-based subtypes were identified, with the notable heterogeneity in prognostic stratification, tumor microenvironment and somatic mutations. The gene signature was generated for risk stratification and prognostic prediction, which was in relation to immunomodulators and immune cells. High-risk cases were more likely to respond to immunotherapy, with distinct pharmacogenomic landscapes between low- and high-risk groups. Higher levels of PAPPA2, MPO, MAGEA11, DEPP1, CPZ, and COLEC12 and lower level of CYTL1 were proven in gastric cancer cells versus controls. Silencing CYTL1 facilitated intracellular ROS accumulation and suppressed migration in gastric cancer cells. Conclusion: Collectively, the DNA damage repair-based classification is a suitable complement to existing molecular classification system, and the quantitative gene signature provides a robust tool in selecting specific therapeutic options.
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Uni- and multivariate Cox regression approaches were utilized for examining whether the RiskScore acted as an independent prognostic parameter.
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LASSO computational approach was adopted for generating a DNA damage repair-relevant gene signature.
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LASSO computational approach was adopted for generating a DNA damage repair-relevant gene signature.
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[337]
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[338]
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[339]
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[340]
GSM2236078
[341]
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[342]
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[344]
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[345]
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[347]
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[348]
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[349]
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[350]
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[351]
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[352]
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[353]
GSM2236092
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[355]
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[356]
GSM2236095
sample_count
357
group_sizes
null
group_sizes_basis
null
platform
6947
taxon
Homo sapiens
title
Molecular subtypes in gastric cancer. [II]
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[4] object · 15 fields
id
data:geo:GSE91061
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=GSE91061
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE91061
version
null
note
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
access_statement_kind
data_availability_statement
sample_accessions array · 109 items
[0]
GSM2420259
[1]
GSM2420260
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GSM2420264
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GSM2420265
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[8]
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GSM2420268
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GSM2420271
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GSM2420275
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[45]
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[63]
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[64]
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[66]
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[67]
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[74]
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[76]
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[107]
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[108]
GSM2420376
sample_count
109
group_sizes
null
group_sizes_basis
null
platform
9052
taxon
Homo sapiens
title
Molecular portraits of tumor mutational and micro-environmental sculpting by immune checkpoint blockade therapy
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 8 items
[0]
asset:data:geo:GSE78220 not downloaded
[1]
asset:data:geo:GSE78220 licence not read
[2]
asset:data:geo:GSE84426 not downloaded
[3]
asset:data:geo:GSE84426 licence not read
[4]
asset:data:geo:GSE84433 not downloaded
[5]
asset:data:geo:GSE84433 licence not read
[6]
asset:data:geo:GSE91061 not downloaded
[7]
asset:data:geo:GSE91061 licence not read
analysis object · 4 fields
state
partial
methods array · 4 items
[0] object · 10 fields
id
method-1
family
survival_analysis
specific
cox_proportional_hazards
label
Survival analysis
dsl_operations array · 1 item
[0]
cox_ph
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
1
band
verbatim
quote
Uni- and multivariate Cox regression approaches were utilized for examining whether the RiskScore acted as an independent prognostic parameter.
[1] object · 10 fields
id
method-2
family
group_comparison
specific
wilcoxon
label
Group comparison
dsl_operations array · 0 items
missing_operations array · 1 item
[0]
group_comparison_wilcoxon
expressible
false
parameters object · 0 fields
data_shapes array · 1 item
[0]
two_or_more_groups_continuous
evidence object · 3 fields
score
0.8
band
high
quote
Wilcoxon
[2] object · 10 fields
id
method-3
family
group_comparison
specific
anova
label
Group comparison
dsl_operations array · 4 items
[0]
group_summary
[1]
welch_t
[2]
bootstrap_mean_difference
[3]
group_comparison_anova
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parameters object · 0 fields
data_shapes array · 1 item
[0]
two_or_more_groups_continuous
evidence object · 3 fields
score
0.8
band
high
quote
ANOVA
[3] object · 10 fields
id
method-4
family
correlation_analysis
specific
spearman
label
Correlation analysis
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[0]
spearman_rho
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
paired_numeric_columns
evidence object · 3 fields
score
0.8
band
high
quote
Spearman correlation
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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
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
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true
required_operations array · 1 item
[0]
cox_ph
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: cox_proportional_hazards.
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]
GSE84426
[1]
GSE84433
[2]
GSE78220
[3]
GSE91061
resolved_accessions array · 4 items
[0]
GSE84426
[1]
GSE84433
[2]
GSE78220
[3]
GSE91061
statements array · 1 item
[0]
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.
basis
The paper names GSE84426, GSE84433, GSE78220, GSE91061 in GSE84426 and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 1 item
[0]
cox_ph
assets array · 2 items
[0]
source:pmid:37124627
[1]
data:geo:GSE78220
steps array · 1 item
[0]
run_analysis
must_build object · 5 fields
dsl_operations array · 0 items
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readers array · 0 items
capabilities array · 0 items
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[0]
data:geo:GSE78220
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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
2026-11-01T18:38:16Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
15246
completion_tokens
2272
cached_tokens
264
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[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
provider
minimax
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review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
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absent
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not_run
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null
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execution.not_run
provenance object · 7 fields
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id
pmid:37124627
type
paper
label
pmid:37124627
[1] object · 3 fields
id
source:pmid:37124627
type
manuscript
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PMID 37124627 full text
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id
data:geo:GSE78220
type
dataset
label
GEO GSE78220
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[0] object · 4 fields
id
activity-reading-sci-2026-11-01
type
classification
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[0] object · 3 fields
id
pmid:37124627
type
paper
label
pmid:37124627
[1] object · 3 fields
id
source:pmid:37124627
type
manuscript
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PMID 37124627 full text
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id
data:geo:GSE78220
type
dataset
label
GEO GSE78220
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-37124627
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extraction
used array · 1 item
[0]
source:pmid:37124627
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE78220
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accession_resolution
used array · 1 item
[0]
data:geo:GSE78220
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agent:corpus-assay-engine
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[0] object · 3 fields
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agent:corpus-assay-engine
type
software
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Corpus assay engine
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id
agent:minimax-reader
type
software
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MiniMax literature reader
source_run_id
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dsl_catalogue_fingerprint
343fb30756ba6ec3
capability_table_fingerprint
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ba34b49490d9bfaf
lineage object · 4 fields
parent_id
pmid:37124627
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sha256:01fb6c3f3c0b2d3383d3b6f9558971c7a2de6319e657bac5c173c15092087bbd
fork_of
null
gaps array · 13 items
[0]
asset:data:geo:GSE78220 licence not read
[1]
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[2]
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[3]
asset:data:geo:GSE84426 not downloaded
[4]
asset:data:geo:GSE84433 licence not read
[5]
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[6]
asset:data:geo:GSE91061 licence not read
[7]
asset:data:geo:GSE91061 not downloaded
[8]
execution.not_run
[9]
method.reader_differs_from_extractor
[10]
review.human_critique
[11]
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[12]
review.machine_critique
assays array · 3 items
[0] object · 11 fields
role
data_generation
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99e1195c7d6f
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partial
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99e1195c7d6f
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evidence array · 2 items
[0]
the DNA damage repair-relevant genes. (A–G) RT-qPCR of the transcriptional levels of PAPPA2, MPO
[1]
e DNA damage repair-relevant genes. (A–G) RT-qPCR of the transcriptional levels of PAPPA2, MPO
order_basis
paper_text_order:4281
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assay:1
[1] object · 11 fields
role
data_generation
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western_blot
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99e1195c7d6f
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99e1195c7d6f
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0.93
evidence array · 1 item
[0]
-1, HGC-27, MKN-28 and AGS cell lines. (H–O) Immunoblotting of the protein levels of PAPPA2, MPO, MAGEA1
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paper_text_order:4425
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assay:2
[2] object · 11 fields
role
analysis
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survival_analysis
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f2132e96ae6c7a4e
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cox_ph
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supported
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dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
Uni- and multivariate Cox regression approaches were utilized for examining whether the RiskScore acted as an independent prognostic parameter.
order_basis
consumes_earlier_output
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37124627", "kind": "science-record", "revision": 3, "content_hash": "sha256:738f24bd5652085545f6b582a73116157fc4c3c0867699b712321fe7cae10dba", "created_at": "2026-11-01T19:01:47Z", "updated_at": "2026-11-01T22:09:22Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Unveiling DNA damage repair-based molecular subtypes, tumor microenvironment and pharmacogenomic landscape in gastric cancer.", "doi": "10.3389/fgene.2023.1118889", "pmid": "37124627", "authors": ["Weiqi Kong", "Zhiqiang Wang", "Bingyi Wang"], "journal": "Frontiers in genetics", "year": 2023, "abstract": "Objective: The current molecular classification system for gastric cancer covers genomic, molecular, and morphological characteristics. Non-etheless, classification of gastric cancer based upon DNA damage repair is still lacking. Here, we defined DNA damage repair-based subtypes across gastric cancer and identified clinicopathological, tumor microenvironment and pharmacogenomic features. Methods: Unsupervised clustering analysis was executed in the TCGA-STAD cohort based upon the transcriptional expression profiling of DNA damage repair genes. LASSO computational approach was adopted for generating a DNA damage repair-relevant gene signature. The identified subtypes or signature were externally verified in the GSE84426 or GSE84433 cohort. The transcriptional levels of immunomodulators, abundance of immune cells and somatic mutations were measured, respectively. Immunotherapeutic response, and drug sensitivity were investigated. The DNA damage repair-relevant genes were further experimentally verified. Results: Two DNA damage repair-based subtypes were identified, with the notable heterogeneity in prognostic stratification, tumor microenvironment and somatic mutations. The gene signature was generated for risk stratification and prognostic prediction, which was in relation to immunomodulators and immune cells. High-risk cases were more likely to respond to immunotherapy, with distinct pharmacogenomic landscapes between low- and high-risk groups. Higher levels of PAPPA2, MPO, MAGEA11, DEPP1, CPZ, and COLEC12 and lower level of CYTL1 were proven in gastric cancer cells versus controls. Silencing CYTL1 facilitated intracellular ROS accumulation and suppressed migration in gastric cancer cells. Conclusion: Collectively, the DNA damage repair-based classification is a suitable complement to existing molecular classification system, and the quantitative gene signature provides a robust tool in selecting specific therapeutic options.", "claims": [{"id": "claim-method", "statement": "Uni- and multivariate Cox regression approaches were utilized for examining whether the RiskScore acted as an independent prognostic parameter.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37124627", "locator": "sections[10] \"Construction of a DNA damage repair-relevant gene signature\" paragraph 2", "quote": "Uni- and multivariate Cox regression approaches were utilized for examining whether the RiskScore acted as an independent prognostic parameter."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37124627", "locator": "sections[35] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "LASSO computational approach was adopted for generating a DNA damage repair-relevant gene signature.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37124627", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "LASSO computational approach was adopted for generating a DNA damage repair-relevant gene signature."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "LASSO computational approach was adopted for generating a DNA damage repair-relevant gene signature.", "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:37124627"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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