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pmid:34920339

Construction and validation of a risk scoring model for diffuse large B-cell lymphoma based on ferroptosis-related genes and its association with immune infiltration.

Dan Xiong · Mojuan Li · Chong Zeng

Translational oncology · 2022 doi:10.1016/j.tranon.2021.101314

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2026-11-01T17:36:38Z
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title
Construction and validation of a risk scoring model for diffuse large B-cell lymphoma based on ferroptosis-related genes and its association with immune infiltration.
doi
10.1016/j.tranon.2021.101314
pmid
34920339
authors array · 3 items
[0]
Dan Xiong
[1]
Mojuan Li
[2]
Chong Zeng
journal
Translational oncology
year
2022
abstract
BACKGROUNDS: The prognostic significance of ferroptosis-related genes is well known. However, survival- and ferroptosis-related genes are not currently considered in risk scoring models for diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS: Ferroptosis regulators and markers were downloaded from the FerrDb database. The transcriptome profiling data were collected from the cancer genome atlas (TCGA). Transcriptome data and corresponding clinical information of DLBCL were downloaded from the gene expression omnibus (GEO). The validation data were downloaded using the UCSC Xena browser. ConsensusClusterPlus was used to categorize DLBCL samples according to gene expression profiles. The survival function was plotted with the Kaplan-Meier plots. The nomogram was built using multivariate logistic regression analysis and the Cox proportional hazards regression model. RESULTS: Based on the GSE11318 dataset of 203 samples and 267 ferroptosis-related gene expression profiles, we identified four clusters. A total of 19 survival-related genes were found associated with ferroptosis. The prognostic risk scoring model was constructed based on the regression coefficients. The obtained area under the receiver operating characteristic curve (AUC) values were 0.769, 0.801, and 0.791 for 1-, 3-, and 5-year survival, respectively. DLBCL samples with cluster 2 or cancer stage IV have shorter survival. Correlations between the immune infiltration and risk scores of the 12 immune cells were demonstrated. The response of DLBCL to doxorubicin was effectively validated by the risk scoring model. CONCLUSIONS: In this study, a ferroptosis-based risk scoring model for patients with DLBCL was constructed and validated in an independent dataset. This risk score model has a better efficacy in predicting survival compared to clinical characteristics.
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Univariable Cox regression analysis was carried out to screen the survival- and ferroptosis- related factors. A least absolute shrinkage and selection operator (LASSO)-type regularization method was used to penalize the factor data. The obtained model shrank the coefficients for non-informative factors toward zero, the reduced variance was acquired, and clustering performance was improved. Prognostic risk scoring models associated with ferroptosis-related factors in DLBCL were constructed based on the regression coefficients of these factors.
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sections[10] "COX-LASSO regression analysis" paragraph 2
quote
Univariable Cox regression analysis was carried out to screen the survival- and ferroptosis- related factors. A least absolute shrinkage and selection operator (LASSO)-type regularization method was used to penalize the factor data. The obtained model shrank the coefficients for non-informative factors toward zero, the reduced variance was acquired, and clustering performance was improved. Prognostic risk scoring models associated with ferroptosis-related factors in DLBCL were constructed based on the regression coefficients of these factors.
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Datasets used and/or analyzed in this study can be obtained from the corresponding author upon reasonable request.
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Datasets used and/or analyzed in this study can be obtained from the corresponding author upon reasonable request.
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The study constructed and externally validated a ferroptosis-based risk scoring model for DLBCL, with AUC values of 0.769, 0.801, and 0.791 for 1-, 3-, and 5-year survival in the development dataset and 0.673, 0.708, and 0.716, respectively, in the independent dataset.
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sections[15] "Identification of ferroptosis and survival-related genes and construction of prognostic risk scoring model" paragraph 2
quote
The prognostic risk scoring model was constructed based on the regression coefficients and calculated as follows, risk Score = -0.006906*DRD4-0.1427*TFAP2C-0.03086*AKR1C3+0.08295*CHAC1+0.2237*ULK2+0.1026*CXCL2-0.2478*GABARAPL1+0.07055*TRIB3-0.01005*CYBB+0.4483*IREB2-0.02139*EPAS1+0.1521*MT1G+0.2654*ATG3-0.06966*CAPG+0.4052*ATF4+0.03599*UBC.
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The obtained area under the receiver operating characteristic curve (AUC) values were 0.769, 0.801, and 0.791 for 1-, 3-, and 5-year survival, respectively.
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sections[17] "Validation of the prognostic scoring model for DLBCL and external confirmation of the nomogram" paragraph 2
quote
The GSE10846 expression profile was input into the model, and the risk scores were obtained.
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sections[17] "Validation of the prognostic scoring model for DLBCL and external confirmation of the nomogram" paragraph 2
quote
The predictive validity of risk scores for 1, 3, and 5 -year survival probability is presented in Fig. 5B, with obtained AUC values of 0.673, 0.708 and 0.716, respectively.
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The study constructed and externally validated a ferroptosis-based risk scoring model for DLBCL, with AUC values of 0.769, 0.801, and 0.791 for 1-, 3-, and 5-year survival in the development dataset and 0.673, 0.708, and 0.716, respectively, in the independent dataset.
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structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
Datasets used and/or analyzed in this study can be obtained from the corresponding author upon reasonable request.
access_statement_kind
data_availability_statement
sample_accessions array · 406 items
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sample_count
406
group_sizes
null
group_sizes_basis
null
platform
570;6400
taxon
Homo sapiens
title
Molecular subtypes of DLBCL have distinct chromosomal aberrations
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 · 4 items
[0]
asset:data:geo:GSE10846 not downloaded
[1]
asset:data:geo:GSE10846 licence not read
[2]
asset:data:geo:GSE11318 not downloaded
[3]
asset:data:geo:GSE11318 licence not read
analysis object · 4 fields
state
complete
methods array · 3 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
Univariable Cox regression analysis was carried out to screen the survival- and ferroptosis- related factors. A least absolute shrinkage and selection operator (LASSO)-type regularization method was used to penalize the factor data. The obtained model shrank the coefficients for non-informative factors toward zero, the reduced variance was acquired, and clustering performance was improved. Prognostic risk scoring models associated with ferroptosis-related factors in DLBCL were constructed based on the regression coefficients of these factors.
[1] object · 10 fields
id
method-2
family
survival_analysis
specific
kaplan_meier
label
Survival analysis
dsl_operations array · 1 item
[0]
survival_km
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parameters object · 0 fields
data_shapes array · 1 item
[0]
time_to_event_with_censoring
evidence object · 3 fields
score
0.7
band
medium
quote
Kaplan-Meier
[2] object · 10 fields
id
method-3
family
regression_modelling
specific
logistic
label
Regression modelling
dsl_operations array · 1 item
[0]
glm_logit_fit
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
predictors_and_outcome
evidence object · 3 fields
score
0.7
band
medium
quote
logistic regression
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]
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[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 · 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 · 2 items
[0]
GSE11318
[1]
GSE10846
resolved_accessions array · 2 items
[0]
GSE11318
[1]
GSE10846
statements array · 1 item
[0]
Datasets used and/or analyzed in this study can be obtained from the corresponding author upon reasonable request.
basis
The paper names GSE11318, GSE10846 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 · 1 item
[0]
cox_ph
assets array · 2 items
[0]
source:pmid:34920339
[1]
data:geo:GSE10846
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:GSE10846
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
2026-11-01T17:11:45Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
9180
completion_tokens
2226
cached_tokens
264
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
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minimax
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[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:34920339
type
paper
label
pmid:34920339
[1] object · 3 fields
id
source:pmid:34920339
type
manuscript
label
PMID 34920339 full text
[2] object · 3 fields
id
data:geo:GSE10846
type
dataset
label
GEO GSE10846
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:34920339
type
paper
label
pmid:34920339
[1] object · 3 fields
id
source:pmid:34920339
type
manuscript
label
PMID 34920339 full text
[2] object · 3 fields
id
data:geo:GSE10846
type
dataset
label
GEO GSE10846
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-34920339
type
extraction
used array · 1 item
[0]
source:pmid:34920339
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE10846
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE10846
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
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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:34920339
parent_hash
sha256:f6b5fb9f157c5c6243ac263b549197087aa381c0c328067c015f239f8cb53847
fork_of
null
gaps array · 8 items
[0]
asset:data:geo:GSE10846 licence not read
[1]
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[2]
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[3]
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[4]
execution.not_run
[5]
review.human_critique
[6]
review.independent_reader
[7]
review.machine_critique
assays array · 1 item
[0] object · 11 fields
role
analysis
definition_id
survival_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 1 item
[0]
cox_ph
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
Univariable Cox regression analysis was carried out to screen the survival- and ferroptosis- related factors. A least absolute shrinkage and selection operator (LASSO)-type regularization method was used to penalize the factor data. The obtained model shrank the coefficients for non-informative factors toward zero, the reduced variance was acquired, and clustering performance was improved. Prognostic risk scoring models associated with ferroptosis-related factors in DLBCL were constructed based on the regression coefficients of these factors.
order_basis
analysis_only
id
assay:1
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34920339", "kind": "science-record", "revision": 3, "content_hash": "sha256:153b2c0f26b9df239c4edd78988141ce4c9f72d9a5df4083ffd86a2d6d8b5e1c", "created_at": "2026-11-01T17:36:38Z", "updated_at": "2026-11-01T21:26:49Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Construction and validation of a risk scoring model for diffuse large B-cell lymphoma based on ferroptosis-related genes and its association with immune infiltration.", "doi": "10.1016/j.tranon.2021.101314", "pmid": "34920339", "authors": ["Dan Xiong", "Mojuan Li", "Chong Zeng"], "journal": "Translational oncology", "year": 2022, "abstract": "BACKGROUNDS: The prognostic significance of ferroptosis-related genes is well known. However, survival- and ferroptosis-related genes are not currently considered in risk scoring models for diffuse large B-cell lymphoma (DLBCL).\nMATERIALS AND METHODS: Ferroptosis regulators and markers were downloaded from the FerrDb database. The transcriptome profiling data were collected from the cancer genome atlas (TCGA). Transcriptome data and corresponding clinical information of DLBCL were downloaded from the gene expression omnibus (GEO). The validation data were downloaded using the UCSC Xena browser. ConsensusClusterPlus was used to categorize DLBCL samples according to gene expression profiles. The survival function was plotted with the Kaplan-Meier plots. The nomogram was built using multivariate logistic regression analysis and the Cox proportional hazards regression model.\nRESULTS: Based on the GSE11318 dataset of 203 samples and 267 ferroptosis-related gene expression profiles, we identified four clusters. A total of 19 survival-related genes were found associated with ferroptosis. The prognostic risk scoring model was constructed based on the regression coefficients. The obtained area under the receiver operating characteristic curve (AUC) values were 0.769, 0.801, and 0.791 for 1-, 3-, and 5-year survival, respectively. DLBCL samples with cluster 2 or cancer stage IV have shorter survival. Correlations between the immune infiltration and risk scores of the 12 immune cells were demonstrated. The response of DLBCL to doxorubicin was effectively validated by the risk scoring model.\nCONCLUSIONS: In this study, a ferroptosis-based risk scoring model for patients with DLBCL was constructed and validated in an independent dataset. This risk score model has a better efficacy in predicting survival compared to clinical characteristics.", "claims": [{"id": "claim-method", "statement": "Univariable Cox regression analysis was carried out to screen the survival- and ferroptosis- related factors. A least absolute shrinkage and selection operator (LASSO)-type regularization method was used to penalize the factor data. The obtained model shrank the coefficients for non-informative factors toward zero, the reduced variance was acquired, and clustering performance was improved. Prognostic risk scoring models associated with ferroptosis-related factors in DLBCL were constructed based on the regression coefficients of these factors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34920339", "locator": "sections[10] \"COX-LASSO regression analysis\" paragraph 2", "quote": "Univariable Cox regression analysis was carried out to screen the survival- and ferroptosis- related factors. A least absolute shrinkage and selection operator (LASSO)-type regularization method was used to penalize the factor data. The obtained model shrank the coefficients for non-informative factors toward zero, the reduced variance was acquired, and clustering performance was improved. Prognostic risk scoring models associated with ferroptosis-related factors in DLBCL were constructed based on the regression coefficients of these factors."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Datasets used and/or analyzed in this study can be obtained from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34920339", "locator": "sections[24] \"ack\" paragraph 1", "quote": "Datasets used and/or analyzed in this study can be obtained from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study constructed and externally validated a ferroptosis-based risk scoring model for DLBCL, with AUC values of 0.769, 0.801, and 0.791 for 1-, 3-, and 5-year survival in the development dataset and 0.673, 0.708, and 0.716, respectively, in the independent dataset.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:34920339", "locator": "sections[15] \"Identification of ferroptosis and survival-related genes and construction of prognostic risk scoring model\" paragraph 2", "quote": "The prognostic risk scoring model was constructed based on the regression coefficients and calculated as follows, risk Score = -0.006906*DRD4-0.1427*TFAP2C-0.03086*AKR1C3+0.08295*CHAC1+0.2237*ULK2+0.1026*CXCL2-0.2478*GABARAPL1+0.07055*TRIB3-0.01005*CYBB+0.4483*IREB2-0.02139*EPAS1+0.1521*MT1G+0.2654*ATG3-0.06966*CAPG+0.4052*ATF4+0.03599*UBC."}, {"asset": "source:pmid:34920339", "locator": "sections[0] \"Abstract\" paragraph 7", "quote": "The obtained area under the receiver operating characteristic curve (AUC) values were 0.769, 0.801, and 0.791 for 1-, 3-, and 5-year survival, respectively."}, {"asset": "source:pmid:34920339", "locator": "sections[17] \"Validation of the prognostic scoring model for DLBCL and external confirmation of the nomogram\" paragraph 2", "quote": "The GSE10846 expression profile was input into the model, and the risk scores were obtained."}, {"asset": "source:pmid:34920339", "locator": "sections[17] \"Validation of the prognostic scoring model for DLBCL and external confirmation of the nomogram\" paragraph 2", "quote": "The predictive validity of risk scores for 1, 3, and 5 -year survival probability is presented in Fig. 5B, with obtained AUC values of 0.673, 0.708 and 0.716, respectively."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study constructed and externally validated a ferroptosis-based risk scoring model for DLBCL, with AUC values of 0.769, 0.801, and 0.791 for 1-, 3-, and 5-year survival in the development dataset and 0.673, 0.708, and 0.716, respectively, in the independent dataset.", "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:34920339"], "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:GSE10846"], "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:GSE10846"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34920339", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.tranon.2021.101314", "sha256": 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"missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Univariable Cox regression analysis was carried out to screen the survival- and ferroptosis- related factors. A least absolute shrinkage and selection operator (LASSO)-type regularization method was used to penalize the factor data. The obtained model shrank the coefficients for non-informative factors toward zero, the reduced variance was acquired, and clustering performance was improved. Prognostic risk scoring models associated with ferroptosis-related factors in DLBCL were constructed based on the regression coefficients of these factors."}}, {"id": "method-2", "family": "survival_analysis", "specific": "kaplan_meier", "label": "Survival analysis", "dsl_operations": ["survival_km"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 0.7, "band": "medium", "quote": "Kaplan-Meier"}}, {"id": "method-3", "family": "regression_modelling", "specific": "logistic", "label": "Regression modelling", "dsl_operations": ["glm_logit_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["predictors_and_outcome"], "evidence": {"score": 0.7, "band": "medium", "quote": "logistic regression"}}], "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": ["cox_ph"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: cox_proportional_hazards."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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