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

pmid:35665757

Low expression of IGFBP4 and TAGLN accelerate the poor overall survival of osteosarcoma.

Yue Xi · Jianlin Liu · Gufeng Shen

Scientific reports · 2022 doi:10.1038/s41598-022-13163-8

Paper

complete

Experiment

complete

Data

partial

Analysis

complete

Execution

absent

Execution evidence has not yet been added to this .science file. Explore its methods, data and open questions to plan the next step.
Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
id
pmid:35665757
kind
science-record
content_hash
sha256:95e5519f89959733a04404dade54a45ae6398f0569d48672fb5982f7fd0b30c7
schema
https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json
created_at
2026-11-01T18:14:37Z
updated_at
2026-11-01T22:06:42Z
generator object · 2 fields
name
corpus-assay-engine
run_id
reading-sci-2026-11-01
paper object · 10 fields
state
complete
title
Low expression of IGFBP4 and TAGLN accelerate the poor overall survival of osteosarcoma.
doi
10.1038/s41598-022-13163-8
pmid
35665757
authors array · 3 items
[0]
Yue Xi
[1]
Jianlin Liu
[2]
Gufeng Shen
journal
Scientific reports
year
2022
abstract
Osteosarcoma is a common malignant bone tumor characterized by the production of osteoid stroma by the tumor. However, effect of IGFBP4 and TAGLN on the survival of osteosarcoma is unclear. The GEO database was used to identify the differentially expressed genes (DEGs) between control samples and osteosarcoma. Genes for biological process (BP), cellular composition (CC), and molecular function (MF) were examined using DAVID, Metascape, and GSEA. GSE14359 and GSE36001 were downloaded in the GEO database. GEO2R was used to find DEGs between control samples and osteosarcoma. The cytoHubb also found the hub genes of IGFBP4 and TAGLN. The Kaplan-Meier method was used to analyze overall survival. A total of 134 patients with osteosarcoma were enrolled in this study. The RNA levels of IGFBP4 and TAGLN were evaluated by RT-qPCR. The correlation between IGFBP4 and TAGLN expression and their associations with clinical indicators were analyzed using Spearman's rho test and Pearson's Chi-squared test. Univariate and multivariate Cox regression analyses were used to determine the potential prognostic factors. And the animal model was used to verify the role of hub genes on the osteosarcoma by the RT-qPCR and immunofluorescence. Support Vector Machine (SVM) was performed to construct the correlation among the expression of IGFBP4, TAGLN, and osteosarcoma. Through bioinformatics, IGFBP4 and TAGLN were identified as the hub genes of osteosarcoma. And osteosarcoma patients with high expression levels of IGFBP4 (HR = 0.56, P = 0.013) and TAGLN (HR = 0.52, P = 0.012) had better overall survival times than those with low expression levels. The results showed that pathologic grade (P = 0.017), tumor metastasis (P < 0.001), and enneking stage (P < 0.001) were significantly correlated with IGFBP4. Also, pathologic grade (P = 0.002), tumor metastasis (P < 0.001), and enneking stage (P < 0.001) were significantly related to the TAGLN. Spearman's correlation coefficient displayed that IGFBP4 were significantly correlated with the tumor metastasis (ρ = - 0.843, P < 0.001), enneking stage (ρ = - 0.500, P < 0.001), and TAGLN (ρ = 0.821, P < 0.001). IGFBP4 (HR = 0.252, 95% CI 0.122-0.517, P < 0.001) and TAGLN (HR = 0.155, 95% CI 0.089-0.269, P < 0.001) were significantly associated with overall survival. Based on the qPCR and immunofluorescence, IGFBP4 and TAGLN were down-regulated in the osteosarcoma tissue than the control group. And the SVM presented that there exists strong relationship among the expression of IGFBP4, TAGLN, and osteosarcoma. IGFBP4 and TAGLN may be attractive molecular targets for osteosarcoma, opening a new avenue for research into the disease.
claims array · 3 items
[0] object · 6 fields
id
claim-method
statement
Univariate and multivariate Cox regression analyses were used to determine the potential prognostic factors.
kind
methodological
target
null
evidence array · 1 item
[0] object · 3 fields
asset
source:pmid:35665757
locator
sections[0] "Abstract" paragraph 1
quote
Univariate and multivariate Cox regression analyses were used to determine the potential prognostic factors.
state
complete
[1] object · 6 fields
id
claim-data-access
statement
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
kind
methodological
target
null
evidence array · 1 item
[0] object · 3 fields
asset
source:pmid:35665757
locator
sections[42] "notes" paragraph 1
quote
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
state
complete
[2] object · 6 fields
id
claim-target-result
statement
Osteosarcoma patients with high expression levels of IGFBP4 (HR = 0.56, P = 0.013) and TAGLN (HR = 0.52, P = 0.012) had better overall survival times than those with low expression levels.
kind
qualitative
target
null
evidence array · 1 item
[0] object · 3 fields
asset
source:pmid:35665757
locator
sections[0] "Abstract" paragraph 1
quote
And osteosarcoma patients with high expression levels of IGFBP4 (HR = 0.56, P = 0.013) and TAGLN (HR = 0.52, P = 0.012) had better overall survival times than those with low expression levels.
state
complete
gaps array · 0 items
experiment object · 8 fields
state
complete
objective
Osteosarcoma patients with high expression levels of IGFBP4 (HR = 0.56, P = 0.013) and TAGLN (HR = 0.52, P = 0.012) had better overall survival times than those with low expression levels.
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:35665757
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:GSE14359
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:GSE14359
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 · 3 items
[0] object · 15 fields
id
source:pmid:35665757
role
manuscript
format
xml
media_type
application/xml
uri
https://doi.org/10.1038/s41598-022-13163-8
sha256
sha256:e12799cf8894a75c1c968965813fefd33be832bd3b6a6ee6be3071840c553b9b
bytes
40489
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
10.1038/s41598-022-13163-8
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
PMC9166812
source
europe_pmc_fulltext
coverage
whole_body_without_references
text_hash_scope
rendered_section_body
[1] object · 15 fields
id
data:geo:GSE14359
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=GSE14359
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE14359
version
null
note
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
access_statement_kind
data_availability_statement
sample_accessions array · 20 items
[0]
GSM359137
[1]
GSM359138
[2]
GSM359139
[3]
GSM359140
[4]
GSM359141
[5]
GSM359142
[6]
GSM359143
[7]
GSM359144
[8]
GSM359145
[9]
GSM359146
[10]
GSM359147
[11]
GSM359148
[12]
GSM359149
[13]
GSM359150
[14]
GSM359151
[15]
GSM359152
[16]
GSM359153
[17]
GSM359154
[18]
GSM359155
[19]
GSM359156
sample_count
20
group_sizes
null
group_sizes_basis
null
platform
96
taxon
Homo sapiens
title
Expression data from conventional osteosarcoma compared to primary non-neoplastic osteoblast cells
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:GSE36001
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=GSE36001
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE36001
version
null
note
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
access_statement_kind
data_availability_statement
sample_accessions array · 25 items
[0]
GSM879156
[1]
GSM879157
[2]
GSM879158
[3]
GSM879159
[4]
GSM879160
[5]
GSM879161
[6]
GSM879162
[7]
GSM879163
[8]
GSM879164
[9]
GSM879165
[10]
GSM879166
[11]
GSM879167
[12]
GSM879168
[13]
GSM879169
[14]
GSM879170
[15]
GSM879171
[16]
GSM879172
[17]
GSM879173
[18]
GSM879174
[19]
GSM879175
[20]
GSM879176
[21]
GSM879177
[22]
GSM879178
[23]
GSM879179
[24]
GSM879180
sample_count
25
group_sizes
null
group_sizes_basis
null
platform
6102
taxon
Homo sapiens
title
Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma [gene expression]
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 · 4 items
[0]
asset:data:geo:GSE14359 not downloaded
[1]
asset:data:geo:GSE14359 licence not read
[2]
asset:data:geo:GSE36001 not downloaded
[3]
asset:data:geo:GSE36001 licence not read
analysis object · 4 fields
state
complete
methods array · 5 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
Univariate and multivariate Cox regression analyses were used to determine the potential prognostic 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
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
machine_learning
specific
support_vector_machine
label
Machine learning
dsl_operations array · 3 items
[0]
train_classifier
[1]
cross_validate
[2]
roc_auc
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
labelled_feature_matrix
evidence object · 3 fields
score
0.7
band
medium
quote
Support Vector Machine
[3] object · 10 fields
id
method-4
family
correlation_analysis
specific
spearman
label
Correlation analysis
dsl_operations array · 1 item
[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
0.7
band
medium
quote
Spearman's correlation
[4] object · 10 fields
id
method-5
family
contingency_analysis
specific
chi_square
label
Categorical (contingency table) analysis
dsl_operations array · 1 item
[0]
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
0.8
band
high
quote
Chi-square
targets array · 0 items
gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 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]
GSE14359
[1]
GSE36001
resolved_accessions array · 2 items
[0]
GSE14359
[1]
GSE36001
statements array · 1 item
[0]
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
basis
The paper names GSE14359, GSE36001 in 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:35665757
[1]
data:geo:GSE14359
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:GSE14359
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
2026-11-01T17:49:24Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
13380
completion_tokens
1557
cached_tokens
128
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:35665757
type
paper
label
pmid:35665757
[1] object · 3 fields
id
source:pmid:35665757
type
manuscript
label
PMID 35665757 full text
[2] object · 3 fields
id
data:geo:GSE14359
type
dataset
label
GEO GSE14359
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:35665757
type
paper
label
pmid:35665757
[1] object · 3 fields
id
source:pmid:35665757
type
manuscript
label
PMID 35665757 full text
[2] object · 3 fields
id
data:geo:GSE14359
type
dataset
label
GEO GSE14359
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-35665757
type
extraction
used array · 1 item
[0]
source:pmid:35665757
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE14359
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE14359
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:35665757
parent_hash
sha256:ace2ba4ab3c034ac1fd72c6ed6c60f5846682427f5112fd213b3eb07090901c5
fork_of
null
gaps array · 8 items
[0]
asset:data:geo:GSE14359 licence not read
[1]
asset:data:geo:GSE14359 not downloaded
[2]
asset:data:geo:GSE36001 licence not read
[3]
asset:data:geo:GSE36001 not downloaded
[4]
execution.not_run
[5]
review.human_critique
[6]
review.independent_reader
[7]
review.machine_critique
assays array · 3 items
[0] object · 11 fields
role
data_generation
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.99
evidence array · 4 items
[0]
levels of IGFBP4 and TAGLN were evaluated by RT-qPCR. The correlation between IGFBP4 and TAGLN ex
[1]
role of hub genes on the osteosarcoma by the RT-qPCR and immunofluorescence. Support Vector Machi
[2]
els of IGFBP4 and TAGLN were evaluated by RT-qPCR. The correlation between IGFBP4 and TAGLN ex
[3]
e of hub genes on the osteosarcoma by the RT-qPCR and immunofluorescence. Support Vector Machi
order_basis
paper_text_order:868
id
assay:1
[1] object · 11 fields
role
data_generation
definition_version
99e1195c7d6f
required_operations array · 0 items
support_state
partial
source_hashes object · 1 field
assay_lexicon
99e1195c7d6f
confidence
0.99
evidence array · 2 items
[0]
genes on the osteosarcoma by the RT-qPCR and immunofluorescence. Support Vector Machine (SVM) was performed
[1]
with overall survival. Based on the qPCR and immunofluorescence, IGFBP4 and TAGLN were down-regulated in the
order_basis
paper_text_order:1259
id
assay:2
[2] 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]
Univariate and multivariate Cox regression analyses were used to determine the potential prognostic factors.
order_basis
consumes_earlier_output
id
assay:3
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35665757", "kind": "science-record", "revision": 4, "content_hash": "sha256:95e5519f89959733a04404dade54a45ae6398f0569d48672fb5982f7fd0b30c7", "created_at": "2026-11-01T18:14:37Z", "updated_at": "2026-11-01T22:06:42Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Low expression of IGFBP4 and TAGLN accelerate the poor overall survival of osteosarcoma.", "doi": "10.1038/s41598-022-13163-8", "pmid": "35665757", "authors": ["Yue Xi", "Jianlin Liu", "Gufeng Shen"], "journal": "Scientific reports", "year": 2022, "abstract": "Osteosarcoma is a common malignant bone tumor characterized by the production of osteoid stroma by the tumor. However, effect of IGFBP4 and TAGLN on the survival of osteosarcoma is unclear. The GEO database was used to identify the differentially expressed genes (DEGs) between control samples and osteosarcoma. Genes for biological process (BP), cellular composition (CC), and molecular function (MF) were examined using DAVID, Metascape, and GSEA. GSE14359 and GSE36001 were downloaded in the GEO database. GEO2R was used to find DEGs between control samples and osteosarcoma. The cytoHubb also found the hub genes of IGFBP4 and TAGLN. The Kaplan-Meier method was used to analyze overall survival. A total of 134 patients with osteosarcoma were enrolled in this study. The RNA levels of IGFBP4 and TAGLN were evaluated by RT-qPCR. The correlation between IGFBP4 and TAGLN expression and their associations with clinical indicators were analyzed using Spearman's rho test and Pearson's Chi-squared test. Univariate and multivariate Cox regression analyses were used to determine the potential prognostic factors. And the animal model was used to verify the role of hub genes on the osteosarcoma by the RT-qPCR and immunofluorescence. Support Vector Machine (SVM) was performed to construct the correlation among the expression of IGFBP4, TAGLN, and osteosarcoma. Through bioinformatics, IGFBP4 and TAGLN were identified as the hub genes of osteosarcoma. And osteosarcoma patients with high expression levels of IGFBP4 (HR = 0.56, P = 0.013) and TAGLN (HR = 0.52, P = 0.012) had better overall survival times than those with low expression levels. The results showed that pathologic grade (P = 0.017), tumor metastasis (P < 0.001), and enneking stage (P < 0.001) were significantly correlated with IGFBP4. Also, pathologic grade (P = 0.002), tumor metastasis (P < 0.001), and enneking stage (P < 0.001) were significantly related to the TAGLN. Spearman's correlation coefficient displayed that IGFBP4 were significantly correlated with the tumor metastasis (ρ = - 0.843, P < 0.001), enneking stage (ρ = - 0.500, P < 0.001), and TAGLN (ρ = 0.821, P < 0.001). IGFBP4 (HR = 0.252, 95% CI 0.122-0.517, P < 0.001) and TAGLN (HR = 0.155, 95% CI 0.089-0.269, P < 0.001) were significantly associated with overall survival. Based on the qPCR and immunofluorescence, IGFBP4 and TAGLN were down-regulated in the osteosarcoma tissue than the control group. And the SVM presented that there exists strong relationship among the expression of IGFBP4, TAGLN, and osteosarcoma. IGFBP4 and TAGLN may be attractive molecular targets for osteosarcoma, opening a new avenue for research into the disease.", "claims": [{"id": "claim-method", "statement": "Univariate and multivariate Cox regression analyses were used to determine the potential prognostic factors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35665757", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Univariate and multivariate Cox regression analyses were used to determine the potential prognostic factors."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35665757", "locator": "sections[42] \"notes\" paragraph 1", "quote": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Osteosarcoma patients with high expression levels of IGFBP4 (HR = 0.56, P = 0.013) and TAGLN (HR = 0.52, P = 0.012) had better overall survival times than those with low expression levels.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35665757", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "And osteosarcoma patients with high expression levels of IGFBP4 (HR = 0.56, P = 0.013) and TAGLN (HR = 0.52, P = 0.012) had better overall survival times than those with low expression levels."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Osteosarcoma patients with high expression levels of IGFBP4 (HR = 0.56, P = 0.013) and TAGLN (HR = 0.52, P = 0.012) had better overall survival times than those with low expression levels.", "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:35665757"], "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:GSE14359"], "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:GSE14359"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35665757", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1038/s41598-022-13163-8", "sha256": "sha256:e12799cf8894a75c1c968965813fefd33be832bd3b6a6ee6be3071840c553b9b", "bytes": 40489, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1038/s41598-022-13163-8", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9166812", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE14359", "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=GSE14359", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE14359", "version": null, "note": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM359137", "GSM359138", "GSM359139", "GSM359140", "GSM359141", "GSM359142", "GSM359143", "GSM359144", "GSM359145", "GSM359146", "GSM359147", "GSM359148", "GSM359149", "GSM359150", "GSM359151", "GSM359152", "GSM359153", "GSM359154", "GSM359155", "GSM359156"], "sample_count": 20, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Expression data from conventional osteosarcoma compared to primary non-neoplastic osteoblast cells", "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:GSE36001", "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=GSE36001", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE36001", "version": null, "note": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM879156", "GSM879157", "GSM879158", "GSM879159", "GSM879160", "GSM879161", "GSM879162", "GSM879163", "GSM879164", "GSM879165", "GSM879166", "GSM879167", "GSM879168", "GSM879169", "GSM879170", "GSM879171", "GSM879172", "GSM879173", "GSM879174", "GSM879175", "GSM879176", "GSM879177", "GSM879178", "GSM879179", "GSM879180"], "sample_count": 25, "group_sizes": null, "group_sizes_basis": null, "platform": "6102", "taxon": "Homo sapiens", "title": "Integrative analysis reveals relationships of genetic and epigenetic alterations in osteosarcoma [gene expression]", "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:GSE14359 not downloaded", "asset:data:geo:GSE14359 licence not read", "asset:data:geo:GSE36001 not downloaded", "asset:data:geo:GSE36001 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "survival_analysis", "specific": "cox_proportional_hazards", "label": "Survival analysis", "dsl_operations": ["cox_ph"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["time_to_event_with_censoring"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Univariate and multivariate Cox regression analyses were used to determine the potential prognostic 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": "machine_learning", "specific": "support_vector_machine", "label": "Machine learning", "dsl_operations": ["train_classifier", "cross_validate", "roc_auc"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 0.7, "band": "medium", "quote": "Support Vector Machine"}}, {"id": "method-4", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.7, "band": "medium", "quote": "Spearman's correlation"}}, {"id": "method-5", "family": "contingency_analysis", "specific": "chi_square", "label": "Categorical (contingency table) analysis", "dsl_operations": ["chi_square_test"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["categorical_cross_tabulation"], "evidence": {"score": 0.8, "band": "high", "quote": "Chi-square"}}], "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. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE14359", "GSE36001"], "resolved_accessions": ["GSE14359", "GSE36001"], "statements": ["The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request."], "basis": "The paper names GSE14359, GSE36001 in GEO and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["cox_ph"], "assets": ["source:pmid:35665757", "data:geo:GSE14359"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE14359"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:49:24Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13380, "completion_tokens": 1557, "cached_tokens": 128}}, "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:35665757", "type": "paper", "label": "pmid:35665757"}, {"id": "source:pmid:35665757", "type": "manuscript", "label": "PMID 35665757 full text"}, {"id": "data:geo:GSE14359", "type": "dataset", "label": "GEO GSE14359"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35665757", "type": "paper", "label": "pmid:35665757"}, {"id": "source:pmid:35665757", "type": "manuscript", "label": "PMID 35665757 full text"}, {"id": "data:geo:GSE14359", "type": "dataset", "label": "GEO GSE14359"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35665757", "type": "extraction", "used": ["source:pmid:35665757"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE14359", "type": "accession_resolution", "used": ["data:geo:GSE14359"], "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:35665757", "parent_hash": "sha256:ace2ba4ab3c034ac1fd72c6ed6c60f5846682427f5112fd213b3eb07090901c5", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE14359 licence not read", "asset:data:geo:GSE14359 not downloaded", "asset:data:geo:GSE36001 licence not read", "asset:data:geo:GSE36001 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["levels of IGFBP4 and TAGLN were evaluated by RT-qPCR. The correlation between IGFBP4 and TAGLN ex", "role of hub genes on the osteosarcoma by the RT-qPCR and immunofluorescence. Support Vector Machi", "els of IGFBP4 and TAGLN were evaluated by RT-qPCR. The correlation between IGFBP4 and TAGLN ex", "e of hub genes on the osteosarcoma by the RT-qPCR and immunofluorescence. Support Vector Machi"], "order_basis": "paper_text_order:868", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["genes on the osteosarcoma by the RT-qPCR and immunofluorescence. Support Vector Machine (SVM) was performed", "with overall survival. Based on the qPCR and immunofluorescence, IGFBP4 and TAGLN were down-regulated in the"], "order_basis": "paper_text_order:1259", "id": "assay:2"}, {"role": "analysis", "definition_id": "survival_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["cox_ph"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Univariate and multivariate Cox regression analyses were used to determine the potential prognostic factors."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}