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

pmid:34513670

RNA Sequence Profiling Reveals Unique Immune and Metabolic Features of Breast Cancer Brain Metastases.

Limei Xiao · Jie Zhou · Hongyi Liu · Yuanyuan Zhou · Weibin Chen · Wugeng Cui · Yilin Zhao

Frontiers in oncology · 2021 doi:10.3389/fonc.2021.679262

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

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:34513670
kind
science-record
content_hash
sha256:1ee79a04f30a4351c71130e3dd9a47d71ff03a1e30dd74f68e5207749769bf38
schema
https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json
created_at
2026-11-01T15:41:51Z
updated_at
2026-11-01T22:47:29Z
generator object · 2 fields
name
corpus-assay-engine
run_id
reading-sci-2026-11-01
paper object · 10 fields
state
complete
title
RNA Sequence Profiling Reveals Unique Immune and Metabolic Features of Breast Cancer Brain Metastases.
doi
10.3389/fonc.2021.679262
pmid
34513670
authors array · 7 items
[0]
Limei Xiao
[1]
Jie Zhou
[2]
Hongyi Liu
[3]
Yuanyuan Zhou
[4]
Weibin Chen
[5]
Wugeng Cui
[6]
Yilin Zhao
journal
Frontiers in oncology
year
2021
abstract
There is an urgent need to improve our understanding of breast cancer brain metastases (BCBMs). Thus, we obtained transcriptome data of BCBMs, primary breast cancers (BCs), and extracranial metastases (BCEMs) from the Gene Expression Omnibus (GEO) database, including GSE43837, GSE14017, and GSE14018, for immune and metabolic analysis. Firstly, we performed immune and metabolic analysis on BCBMs and primary breast cancers of GSE43837 using RNA sequence. We identified significant immunosuppression and gene signatures associated with immune infiltration in BCBMs; the lower the expression of the signatures, the worse the prognosis of breast cancer patients in the Kaplan-Meier (KM) plotter [Breast cancer] database. We also identified increased oxidative phosphorylation (OXPHOS) utilization in BCBMs compared with BCs and gene signatures associated with increased OXPHOS utilization in BCBMs; the higher the expression of the signatures, the worse the prognosis of breast cancer patients in the KM plotter [Breast cancer] database, which can predict the prognosis of breast cancer patients better, as it can also predict the prognosis of patients with different breast cancer subtypes. In addition, we performed immune and metabolic analysis on BCBMs and extracranial metastases of GSE14017 and GSE14018 using RNA sequence. Compared with extracranial metastases, we identified more significant immunosuppression but no difference in OXPHOS utilization in BCBMs, which may be because OXPHOS was also involved in extracranial metastases. We have proven that OXPHOS was functionally significant in metastasis in vitro assays. Oligomycin, an OXPHOS inhibitor, substantially attenuated the migration and invasion potential of breast cancer cells. Our study provides new insights into the pathogenesis of BCBMs. SIGNIFICANCE: Our study reports the most comprehensive gene expression analysis of BCBMs, BCs and extracranial metastases to date. We identified immunosuppression and OXPHOS enrichment in BCBMs compared with BCs, which provide new insights into the pathogenesis of BCBMs and will facilitate the development of new therapeutic strategies for patients with BCBMs.
claims array · 2 items
[0] object · 6 fields
id
claim-method
statement
p-values are determined by the Fisher’s exact test in DAVID.
kind
methodological
target
null
evidence array · 1 item
[0] object · 3 fields
asset
source:pmid:34513670
locator
sections[7] "Functional Enrichment Analysis of DEGs" paragraph 2
quote
p-values are determined by the Fisher’s exact test in DAVID.
state
complete
[1] object · 6 fields
id
claim-data-access
statement
The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files or from the corresponding author on reasonable request. All RNA-seq data files that were reanalysed here are available in the GEO database under the following accession codes: GSE43837, GSE14017 and GSE14018.
kind
methodological
target
null
evidence array · 1 item
[0] object · 3 fields
asset
source:pmid:34513670
locator
sections[23] "Data Availability Statement" paragraph 2
quote
The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files or from the corresponding author on reasonable request. All RNA-seq data files that were reanalysed here are available in the GEO database under the following accession codes: GSE43837, GSE14017 and GSE14018.
state
complete
gaps array · 0 items
experiment object · 8 fields
state
complete
objective
null
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:34513670
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:GSE14017
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:GSE14017
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:34513670
role
manuscript
format
xml
media_type
application/xml
uri
https://doi.org/10.3389/fonc.2021.679262
sha256
sha256:0ef82084b39b80936f30db00384ba98408c43e7f9ba9f0b6b4aa4d1249c4b815
bytes
62517
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
10.3389/fonc.2021.679262
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
PMC8427193
source
europe_pmc_fulltext
coverage
whole_body
text_hash_scope
rendered_section_body
[1] object · 15 fields
id
data:geo:GSE14017
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=GSE14017
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE14017
version
null
note
The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files or from the corresponding author on reasonable request. All RNA-seq data files that were reanalysed here are available in the GEO database under the following accession codes: GSE43837, GSE14017 and GSE14018.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files or from the corresponding author on reasonable request. All RNA-seq data files that were reanalysed here are available in the GEO database under the following accession codes: GSE43837, GSE14017 and GSE14018.
access_statement_kind
data_availability_statement
sample_accessions array · 29 items
[0]
GSM352095
[1]
GSM352097
[2]
GSM352098
[3]
GSM352100
[4]
GSM352101
[5]
GSM352103
[6]
GSM352105
[7]
GSM352107
[8]
GSM352109
[9]
GSM352110
[10]
GSM352111
[11]
GSM352113
[12]
GSM352114
[13]
GSM352115
[14]
GSM352117
[15]
GSM352119
[16]
GSM352120
[17]
GSM352121
[18]
GSM352122
[19]
GSM352123
[20]
GSM352124
[21]
GSM352125
[22]
GSM352126
[23]
GSM352127
[24]
GSM352128
[25]
GSM352129
[26]
GSM352130
[27]
GSM352131
[28]
GSM352132
sample_count
29
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Metastases of breast cancer (U133plus2)
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[2] object · 15 fields
id
data:geo:GSE14018
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=GSE14018
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE14018
version
null
note
The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files or from the corresponding author on reasonable request. All RNA-seq data files that were reanalysed here are available in the GEO database under the following accession codes: GSE43837, GSE14017 and GSE14018.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files or from the corresponding author on reasonable request. All RNA-seq data files that were reanalysed here are available in the GEO database under the following accession codes: GSE43837, GSE14017 and GSE14018.
access_statement_kind
data_availability_statement
sample_accessions array · 36 items
[0]
GSM352133
[1]
GSM352134
[2]
GSM352135
[3]
GSM352136
[4]
GSM352137
[5]
GSM352138
[6]
GSM352139
[7]
GSM352140
[8]
GSM352141
[9]
GSM352142
[10]
GSM352143
[11]
GSM352144
[12]
GSM352145
[13]
GSM352146
[14]
GSM352147
[15]
GSM352148
[16]
GSM352149
[17]
GSM352150
[18]
GSM352151
[19]
GSM352152
[20]
GSM352153
[21]
GSM352154
[22]
GSM352155
[23]
GSM352156
[24]
GSM352157
[25]
GSM352158
[26]
GSM352159
[27]
GSM352160
[28]
GSM352161
[29]
GSM352162
[30]
GSM352163
[31]
GSM352164
[32]
GSM352165
[33]
GSM352166
[34]
GSM352167
[35]
GSM352168
sample_count
36
group_sizes
null
group_sizes_basis
null
platform
96
taxon
Homo sapiens
title
Metastases of breast cancer (U133A)
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[3] object · 15 fields
id
data:geo:GSE43837
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=GSE43837
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE43837
version
null
note
The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files or from the corresponding author on reasonable request. All RNA-seq data files that were reanalysed here are available in the GEO database under the following accession codes: GSE43837, GSE14017 and GSE14018.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files or from the corresponding author on reasonable request. All RNA-seq data files that were reanalysed here are available in the GEO database under the following accession codes: GSE43837, GSE14017 and GSE14018.
access_statement_kind
data_availability_statement
sample_accessions array · 38 items
[0]
GSM1071862
[1]
GSM1071863
[2]
GSM1071864
[3]
GSM1071865
[4]
GSM1071866
[5]
GSM1071867
[6]
GSM1071868
[7]
GSM1071869
[8]
GSM1071870
[9]
GSM1071871
[10]
GSM1071872
[11]
GSM1071873
[12]
GSM1071874
[13]
GSM1071875
[14]
GSM1071876
[15]
GSM1071877
[16]
GSM1071878
[17]
GSM1071879
[18]
GSM1071880
[19]
GSM1071881
[20]
GSM1071882
[21]
GSM1071883
[22]
GSM1071884
[23]
GSM1071885
[24]
GSM1071886
[25]
GSM1071887
[26]
GSM1071888
[27]
GSM1071889
[28]
GSM1071890
[29]
GSM1071891
[30]
GSM1071892
[31]
GSM1071893
[32]
GSM1071894
[33]
GSM1071895
[34]
GSM1071896
[35]
GSM1071897
[36]
GSM1071898
[37]
GSM1071899
sample_count
38
group_sizes
null
group_sizes_basis
null
platform
1352
taxon
Homo sapiens
title
A BRCA1 Deficient-Like Signature is Enriched in Breast Cancer Brain Metastases
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 6 items
[0]
asset:data:geo:GSE14017 not downloaded
[1]
asset:data:geo:GSE14017 licence not read
[2]
asset:data:geo:GSE14018 not downloaded
[3]
asset:data:geo:GSE14018 licence not read
[4]
asset:data:geo:GSE43837 not downloaded
[5]
asset:data:geo:GSE43837 licence not read
analysis object · 4 fields
state
partial
methods array · 3 items
[0] object · 10 fields
id
method-1
family
contingency_analysis
specific
fisher_exact
label
Categorical (contingency table) analysis
dsl_operations array · 2 items
[0]
contingency_table
[1]
chi_square_test
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
categorical_cross_tabulation
evidence object · 3 fields
score
1
band
verbatim
quote
p-values are determined by the Fisher’s exact test in DAVID.
[1] object · 10 fields
id
method-2
family
survival_analysis
specific
kaplan_meier
label
Survival analysis
dsl_operations array · 1 item
[0]
survival_km
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
0.7
band
medium
quote
Kaplan-Meier
[2] object · 10 fields
id
method-3
family
differential_expression
specific
edger
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
0.8
band
high
quote
edgeR
targets array · 0 items
gaps array · 1 item
[0]
method.reader_differs_from_extractor
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 2 items
[0]
contingency_table
[1]
chi_square_test
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: fisher_exact.
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]
GSE43837
[1]
GSE14017
[2]
GSE14018
resolved_accessions array · 3 items
[0]
GSE43837
[1]
GSE14017
[2]
GSE14018
statements array · 1 item
[0]
The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files or from the corresponding author on reasonable request. All RNA-seq data files that were reanalysed here are available in the GEO database under the following accession codes: GSE43837, GSE14017 and GSE14018.
basis
The paper names GSE43837, GSE14017, GSE14018 in National Central of Biology Information 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 · 2 items
[0]
contingency_table
[1]
chi_square_test
assets array · 2 items
[0]
source:pmid:34513670
[1]
data:geo:GSE14017
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:GSE14017
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
2026-10-31T18:34:42Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
49927
completion_tokens
2446
cached_tokens
776
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:34513670
type
paper
label
pmid:34513670
[1] object · 3 fields
id
source:pmid:34513670
type
manuscript
label
PMID 34513670 full text
[2] object · 3 fields
id
data:geo:GSE14017
type
dataset
label
GEO GSE14017
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:34513670
type
paper
label
pmid:34513670
[1] object · 3 fields
id
source:pmid:34513670
type
manuscript
label
PMID 34513670 full text
[2] object · 3 fields
id
data:geo:GSE14017
type
dataset
label
GEO GSE14017
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-34513670
type
extraction
used array · 1 item
[0]
source:pmid:34513670
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE14017
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE14017
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:34513670
parent_hash
sha256:1684c25bb5296114399b7553d6a233cef7907ee16ad79aa263ba47b18a315c5a
fork_of
null
gaps array · 11 items
[0]
asset:data:geo:GSE14017 licence not read
[1]
asset:data:geo:GSE14017 not downloaded
[2]
asset:data:geo:GSE14018 licence not read
[3]
asset:data:geo:GSE14018 not downloaded
[4]
asset:data:geo:GSE43837 licence not read
[5]
asset:data:geo:GSE43837 not downloaded
[6]
execution.not_run
[7]
method.reader_differs_from_extractor
[8]
review.human_critique
[9]
review.independent_reader
[10]
review.machine_critique
assays array · 2 items
[0] object · 11 fields
role
data_generation
definition_id
cell_culture
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.77
evidence array · 1 item
[0]
& Technology Co. Ltd. MDA-MB-231 cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM; Ba
order_basis
paper_text_order:3093
id
assay:1
[1] object · 11 fields
role
analysis
definition_id
contingency_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 2 items
[0]
contingency_table
[1]
chi_square_test
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
p-values are determined by the Fisher’s exact test in DAVID.
order_basis
consumes_earlier_output
id
assay:2
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34513670", "kind": "science-record", "revision": 8, "content_hash": "sha256:1ee79a04f30a4351c71130e3dd9a47d71ff03a1e30dd74f68e5207749769bf38", "created_at": "2026-11-01T15:41:51Z", "updated_at": "2026-11-01T22:47:29Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "RNA Sequence Profiling Reveals Unique Immune and Metabolic Features of Breast Cancer Brain Metastases.", "doi": "10.3389/fonc.2021.679262", "pmid": "34513670", "authors": ["Limei Xiao", "Jie Zhou", "Hongyi Liu", "Yuanyuan Zhou", "Weibin Chen", "Wugeng Cui", "Yilin Zhao"], "journal": "Frontiers in oncology", "year": 2021, "abstract": "There is an urgent need to improve our understanding of breast cancer brain metastases (BCBMs). Thus, we obtained transcriptome data of BCBMs, primary breast cancers (BCs), and extracranial metastases (BCEMs) from the Gene Expression Omnibus (GEO) database, including GSE43837, GSE14017, and GSE14018, for immune and metabolic analysis. Firstly, we performed immune and metabolic analysis on BCBMs and primary breast cancers of GSE43837 using RNA sequence. We identified significant immunosuppression and gene signatures associated with immune infiltration in BCBMs; the lower the expression of the signatures, the worse the prognosis of breast cancer patients in the Kaplan-Meier (KM) plotter [Breast cancer] database. We also identified increased oxidative phosphorylation (OXPHOS) utilization in BCBMs compared with BCs and gene signatures associated with increased OXPHOS utilization in BCBMs; the higher the expression of the signatures, the worse the prognosis of breast cancer patients in the KM plotter [Breast cancer] database, which can predict the prognosis of breast cancer patients better, as it can also predict the prognosis of patients with different breast cancer subtypes. In addition, we performed immune and metabolic analysis on BCBMs and extracranial metastases of GSE14017 and GSE14018 using RNA sequence. Compared with extracranial metastases, we identified more significant immunosuppression but no difference in OXPHOS utilization in BCBMs, which may be because OXPHOS was also involved in extracranial metastases. We have proven that OXPHOS was functionally significant in metastasis in vitro assays. Oligomycin, an OXPHOS inhibitor, substantially attenuated the migration and invasion potential of breast cancer cells. Our study provides new insights into the pathogenesis of BCBMs.\nSIGNIFICANCE: Our study reports the most comprehensive gene expression analysis of BCBMs, BCs and extracranial metastases to date. We identified immunosuppression and OXPHOS enrichment in BCBMs compared with BCs, which provide new insights into the pathogenesis of BCBMs and will facilitate the development of new therapeutic strategies for patients with BCBMs.", "claims": [{"id": "claim-method", "statement": "p-values are determined by the Fisher’s exact test in DAVID.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34513670", "locator": "sections[7] \"Functional Enrichment Analysis of DEGs\" paragraph 2", "quote": "p-values are determined by the Fisher’s exact test in DAVID."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files or from the corresponding author on reasonable request. All RNA-seq data files that were reanalysed here are available in the GEO database under the following accession codes: GSE43837, GSE14017 and GSE14018.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34513670", "locator": "sections[23] \"Data Availability Statement\" paragraph 2", "quote": "The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files or from the corresponding author on reasonable request. All RNA-seq data files that were reanalysed here are available in the GEO database under the following accession codes: GSE43837, GSE14017 and GSE14018."}], "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:34513670"], "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:GSE14017"], "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:GSE14017"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34513670", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fonc.2021.679262", "sha256": "sha256:0ef82084b39b80936f30db00384ba98408c43e7f9ba9f0b6b4aa4d1249c4b815", "bytes": 62517, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fonc.2021.679262", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8427193", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE14017", "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=GSE14017", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE14017", "version": null, "note": "The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files or from the corresponding author on reasonable request. All RNA-seq data files that were reanalysed here are available in the GEO database under the following accession codes: GSE43837, GSE14017 and GSE14018.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files or from the corresponding author on reasonable request. All RNA-seq data files that were reanalysed here are available in the GEO database under the following accession codes: GSE43837, GSE14017 and GSE14018.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM352095", "GSM352097", "GSM352098", "GSM352100", "GSM352101", "GSM352103", "GSM352105", "GSM352107", "GSM352109", "GSM352110", "GSM352111", "GSM352113", "GSM352114", "GSM352115", "GSM352117", "GSM352119", "GSM352120", "GSM352121", "GSM352122", "GSM352123", "GSM352124", "GSM352125", "GSM352126", "GSM352127", "GSM352128", "GSM352129", "GSM352130", "GSM352131", "GSM352132"], "sample_count": 29, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Metastases of breast cancer (U133plus2)", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE14018", "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=GSE14018", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE14018", "version": null, "note": "The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files or from the corresponding author on reasonable request. All RNA-seq data files that were reanalysed here are available in the GEO database under the following accession codes: GSE43837, GSE14017 and GSE14018.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files or from the corresponding author on reasonable request. All RNA-seq data files that were reanalysed here are available in the GEO database under the following accession codes: GSE43837, GSE14017 and GSE14018.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM352133", "GSM352134", "GSM352135", "GSM352136", "GSM352137", "GSM352138", "GSM352139", "GSM352140", "GSM352141", "GSM352142", "GSM352143", "GSM352144", "GSM352145", "GSM352146", "GSM352147", "GSM352148", "GSM352149", "GSM352150", "GSM352151", "GSM352152", "GSM352153", "GSM352154", "GSM352155", "GSM352156", "GSM352157", "GSM352158", "GSM352159", "GSM352160", "GSM352161", "GSM352162", "GSM352163", "GSM352164", "GSM352165", "GSM352166", "GSM352167", "GSM352168"], "sample_count": 36, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Metastases of breast cancer (U133A)", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE43837", "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=GSE43837", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE43837", "version": null, "note": "The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files or from the corresponding author on reasonable request. All RNA-seq data files that were reanalysed here are available in the GEO database under the following accession codes: GSE43837, GSE14017 and GSE14018.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files or from the corresponding author on reasonable request. All RNA-seq data files that were reanalysed here are available in the GEO database under the following accession codes: GSE43837, GSE14017 and GSE14018.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1071862", "GSM1071863", "GSM1071864", "GSM1071865", "GSM1071866", "GSM1071867", "GSM1071868", "GSM1071869", "GSM1071870", "GSM1071871", "GSM1071872", "GSM1071873", "GSM1071874", "GSM1071875", "GSM1071876", "GSM1071877", "GSM1071878", "GSM1071879", "GSM1071880", "GSM1071881", "GSM1071882", "GSM1071883", "GSM1071884", "GSM1071885", "GSM1071886", "GSM1071887", "GSM1071888", "GSM1071889", "GSM1071890", "GSM1071891", "GSM1071892", "GSM1071893", "GSM1071894", "GSM1071895", "GSM1071896", "GSM1071897", "GSM1071898", "GSM1071899"], "sample_count": 38, "group_sizes": null, "group_sizes_basis": null, "platform": "1352", "taxon": "Homo sapiens", "title": "A BRCA1 Deficient-Like Signature is Enriched in Breast Cancer Brain Metastases", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE14017 not downloaded", "asset:data:geo:GSE14017 licence not read", "asset:data:geo:GSE14018 not downloaded", "asset:data:geo:GSE14018 licence not read", "asset:data:geo:GSE43837 not downloaded", "asset:data:geo:GSE43837 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "contingency_analysis", "specific": "fisher_exact", "label": "Categorical (contingency table) analysis", "dsl_operations": ["contingency_table", "chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "p-values are determined by the Fisher’s exact test in DAVID."}}, {"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": "differential_expression", "specific": "edger", "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": 0.8, "band": "high", "quote": "edgeR"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "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": ["contingency_table", "chi_square_test"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: fisher_exact."}, "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": ["GSE43837", "GSE14017", "GSE14018"], "resolved_accessions": ["GSE43837", "GSE14017", "GSE14018"], "statements": ["The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files or from the corresponding author on reasonable request. All RNA-seq data files that were reanalysed here are available in the GEO database under the following accession codes: GSE43837, GSE14017 and GSE14018."], "basis": "The paper names GSE43837, GSE14017, GSE14018 in National Central of Biology Information 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": ["contingency_table", "chi_square_test"], "assets": ["source:pmid:34513670", "data:geo:GSE14017"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE14017"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:34:42Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 49927, "completion_tokens": 2446, "cached_tokens": 776}}, "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:34513670", "type": "paper", "label": "pmid:34513670"}, {"id": "source:pmid:34513670", "type": "manuscript", "label": "PMID 34513670 full text"}, {"id": "data:geo:GSE14017", "type": "dataset", "label": "GEO GSE14017"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34513670", "type": "paper", "label": "pmid:34513670"}, {"id": "source:pmid:34513670", "type": "manuscript", "label": "PMID 34513670 full text"}, {"id": "data:geo:GSE14017", "type": "dataset", "label": "GEO GSE14017"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34513670", "type": "extraction", "used": ["source:pmid:34513670"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE14017", "type": "accession_resolution", "used": ["data:geo:GSE14017"], "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:34513670", "parent_hash": "sha256:1684c25bb5296114399b7553d6a233cef7907ee16ad79aa263ba47b18a315c5a", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE14017 licence not read", "asset:data:geo:GSE14017 not downloaded", "asset:data:geo:GSE14018 licence not read", "asset:data:geo:GSE14018 not downloaded", "asset:data:geo:GSE43837 licence not read", "asset:data:geo:GSE43837 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["& Technology Co. Ltd. MDA-MB-231 cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM; Ba"], "order_basis": "paper_text_order:3093", "id": "assay:1"}, {"role": "analysis", "definition_id": "contingency_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["contingency_table", "chi_square_test"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["p-values are determined by the Fisher’s exact test in DAVID."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}