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pmid:32309427

Identification of Four Pathological Stage-Relevant Genes in Association with Progression and Prognosis in Clear Cell Renal Cell Carcinoma by Integrated Bioinformatics Analysis.

Dengyong Xu · Yuzi Xu · Yiming Lv · Fei Wu · Yunlong Liu · Ming Zhu · Dake Chen · Bingjun Bai

BioMed research international · 2020 doi:10.1155/2020/2137319

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Experiment

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title
Identification of Four Pathological Stage-Relevant Genes in Association with Progression and Prognosis in Clear Cell Renal Cell Carcinoma by Integrated Bioinformatics Analysis.
doi
10.1155/2020/2137319
pmid
32309427
authors array · 8 items
[0]
Dengyong Xu
[1]
Yuzi Xu
[2]
Yiming Lv
[3]
Fei Wu
[4]
Yunlong Liu
[5]
Ming Zhu
[6]
Dake Chen
[7]
Bingjun Bai
journal
BioMed research international
year
2020
abstract
Clear cell renal cell carcinoma (ccRCC) is a major histological subtype of renal cell carcinoma and can be clinically divided into four stages according to the TNM criteria. Identifying clinical stage-related genes is beneficial for improving the early diagnosis and prognosis of ccRCC. By using bioinformatics analysis, we aim to identify clinical stage-relevant genes that are significantly associated with the development of ccRCC. First, we analyzed the gene expression microarray data sets: GSE53757 and GSE73731. We divided these data into five groups by staging information-normal tissue and ccRCC stages I, II, III, and IV-and eventually identified 500 differentially expressed genes (DEGs). To obtain precise stage-relevant genes, we subsequently applied weighted gene coexpression network analysis (WGCNA) to the GSE73731 dataset and KIRC data from The Cancer Genome Atlas (TCGA). Two modules from each dataset were identified to be related to the tumor TNM stage. Several genes with high inner connection inside the modules were considered hub genes. The intersection results between hub genes of key modules and 500 DEGs revealed UBE2C, BUB1B, RRM2, and TPX2 as highly associated with the stage of ccRCC. In addition, the candidate genes were validated at both the RNA expression level and the protein level. Survival analysis also showed that 4 genes were significantly correlated with overall survival. In conclusion, our study affords a deeper understanding of the molecular mechanisms associated with the development of ccRCC and provides potential biomarkers for early diagnosis and individualized treatment for patients at different stages of ccRCC.
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The gene expression levels in ccRCC stages I, II, III, and IV were compared with those in normal tissue using the limma package [33] in R software.
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The gene expression levels in ccRCC stages I, II, III, and IV were compared with those in normal tissue using the limma package [33] in R software.
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Clear cell renal cell carcinoma (ccRCC) samples
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TPX2
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F: 5′- ATGGAACTGGAGGGCTTTTTC -3′
[8] array · 1 item
[0]
R: 5′- TGTTGTCAACTGGTTTCAAAGGT -3′
[9] array · 2 items
[0]
β-Actin
[1]
F: 5′- ACTCTTCCAGCCTTCCTTCC -3′
[10] array · 1 item
[0]
R: 5′- CGTCATACTCCTGCTTGCTG -3′
locator
section[13]/table-wrap[1]#tab1
[4] object · 16 fields
id
asset:table:pmid:32309427:2
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:2235023330f468cdca395f4a7a00379138adaf6ed38925b5a4006c067024ad58
bytes
451
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[16]/table-wrap[1]#tab2
version
null
note
GSE datasets involved in our study.
structure object · 5 fields
pmcid
PMC7142335
section_index
16
section_title
3.1. Basic Characteristics of Microarray Data
row_count
7
column_count
3
table object · 8 fields
label
Table 2
caption
GSE datasets involved in our study.
rows array · 7 items
[0] array · 3 items
[0]
Group
[1]
Quantity
[2]
GSE datasets
[1] array · 3 items
[0]
Normal tissues
[1]
72
[2]
GSE53757
[2] array · 3 items
[0]
ccRCC stage I
[1]
62
[2]
GSE53757+GSE73731
[3] array · 3 items
[0]
ccRCC stage II
[1]
29
[2]
GSE53757+GSE73731
[4] array · 3 items
[0]
ccRCC stage III
[1]
41
[2]
GSE53757+GSE73731
[5] array · 3 items
[0]
ccRCC stage IV
[1]
57
[2]
GSE53757+GSE73731
[6] array · 3 items
[0]
Total
[1]
261
[2]
locator
section[16]/table-wrap[1]#tab2
[5] object · 16 fields
id
asset:table:pmid:32309427:3
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:8ade9c4dbdf817c489c1bda3254d609f6de0406b1e457803690b1e0accffdce1
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691
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open
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verified
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read_table
reader_status
available
identifier
section[21]/table-wrap[1]#tab3
version
null
note
Four key hub genes selected from among 500 DEGs and 21 common hub genes from GSE73731 and TCGA-KIRC data.
structure object · 5 fields
pmcid
PMC7142335
section_index
21
section_title
3.6. Weighted Gene Coexpression Network Analysis Using TCGA-KIRC Dataset and Filtration of Hub Genes
row_count
5
column_count
6
table object · 8 fields
label
Table 3
caption
Four key hub genes selected from among 500 DEGs and 21 common hub genes from GSE73731 and TCGA-KIRC data.
rows array · 5 items
[0] array · 6 items
[0]
Gene symbol
[1]
Description
[2]
Log FC in stage I
[3]
Log FC in stage II
[4]
Log FC in stage III
[5]
Log FC in stage IV
[1] array · 6 items
[0]
UBE2C
[1]
Ubiquitin-conjugating enzyme E2C
[2]
2.92
[3]
2.60
[4]
3.68
[5]
3.76
[2] array · 6 items
[0]
BUB1B
[1]
BUB1 mitotic checkpoint serine/threonine kinase B
[2]
3.07
[3]
2.24
[4]
3.26
[5]
3.19
[3] array · 6 items
[0]
RRM2
[1]
Ribonucleotide reductase regulatory subunit M2
[2]
3.08
[3]
2.9
[4]
3.74
[5]
4.10
[4] array · 6 items
[0]
TPX2
[1]
TPX2 microtubule nucleation factor
[2]
2.59
[3]
2.51
[4]
3.14
[5]
3.50
locator
section[21]/table-wrap[1]#tab3
[6] object · 16 fields
id
asset:table:pmid:32309427:4
role
table
format
jats-table
media_type
application/vnd.jats.table+json
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null
sha256
sha256:10220fdb08290a060093ee538dbb3ecd3c70d59cb4fd05a28f6efd3c036d3785
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742
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read_table
reader_status
available
identifier
section[22]/table-wrap[1]#tab4
version
null
note
Histopathological characteristics of the ccRCC patients.
structure object · 5 fields
pmcid
PMC7142335
section_index
22
section_title
3.7. Validation of RNA and Protein Expression Level for Key Hub Genes
row_count
9
column_count
7
table object · 8 fields
label
Table 4
caption
Histopathological characteristics of the ccRCC patients.
rows array · 9 items
[0] array · 7 items
[0]
Patient
[1]
Sex
[2]
Age (years)
[3]
Pathology
[4]
Location
[5]
Tumor size (cm)
[6]
Stage
[1] array · 7 items
[0]
1
[1]
Male
[2]
65
[3]
ccRCC, partially PRCC
[4]
Left
[5]
12∗10.5
[6]
III
[2] array · 7 items
[0]
2
[1]
Male
[2]
80
[3]
ccRCC
[4]
Left
[5]
14.8∗9.8
[6]
IV
[3] array · 7 items
[0]
3
[1]
Female
[2]
58
[3]
ccRCC, partially PRCC
[4]
Left
[5]
7∗4∗2.5
[6]
I
[4] array · 7 items
[0]
4
[1]
Male
[2]
63
[3]
ccRCC
[4]
Right
[5]
4.5∗4.5
[6]
IV
[5] array · 7 items
[0]
5
[1]
Female
[2]
81
[3]
ccRCC, partially PRCC
[4]
Left
[5]
3∗2.2
[6]
I
[6] array · 7 items
[0]
6
[1]
Female
[2]
56
[3]
ccRCC
[4]
Right
[5]
2.5∗3.1
[6]
IV
[7] array · 7 items
[0]
7
[1]
Male
[2]
57
[3]
ccRCC
[4]
Right
[5]
5∗4.5
[6]
II
[8] array · 7 items
[0]
8
[1]
Male
[2]
34
[3]
ccRCC
[4]
Right
[5]
3.5∗3.2
[6]
I
locator
section[22]/table-wrap[1]#tab4
[7] object · 16 fields
id
asset:table:pmid:32309427:5
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:d4d4cdec6e29e14542a6ce514aef9c93acff7c760d958abe1e1be4b349bb131b
bytes
807
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reader
read_table
reader_status
available
identifier
section[22]/table-wrap[2]#tab5
version
null
note
IHC staining characteristics of hub genes from the Human Protein Atlas database.
structure object · 5 fields
pmcid
PMC7142335
section_index
22
section_title
3.7. Validation of RNA and Protein Expression Level for Key Hub Genes
row_count
9
column_count
8
table object · 8 fields
label
Table 5
caption
IHC staining characteristics of hub genes from the Human Protein Atlas database.
rows array · 9 items
[0] array · 8 items
[0]
Gene
[1]
Patient ID
[2]
Gender
[3]
Age (years)
[4]
Staining
[5]
Intensity
[6]
Quantity
[7]
Location
[1] array · 1 item
[0]
Normal tissues
[2] array · 8 items
[0]
UBE2C
[1]
3229
[2]
Male
[3]
59
[4]
Medium
[5]
Moderate
[6]
>75%
[7]
CytoplasmicMembranousNuclear
[3] array · 8 items
[0]
RRM2
[1]
1859
[2]
Male
[3]
61
[4]
Not detected
[5]
Negative
[6]
None
[7]
None
[4] array · 8 items
[0]
TPX2
[1]
1933
[2]
Female
[3]
56
[4]
Low
[5]
Weak
[6]
25-75%
[7]
CytoplasmicMembranous
[5] array · 1 item
[0]
Cancerous tissues
[6] array · 8 items
[0]
UBE2C
[1]
2540
[2]
Male
[3]
61
[4]
High
[5]
Strong
[6]
>75%
[7]
CytoplasmicMembranousNuclear
[7] array · 8 items
[0]
RRM2
[1]
3616
[2]
Female
[3]
63
[4]
Not detected
[5]
Negative
[6]
None
[7]
None
[8] array · 8 items
[0]
TPX2
[1]
1831
[2]
Male
[3]
77
[4]
Medium
[5]
Strong
[6]
25%
[7]
Nuclear
locator
section[22]/table-wrap[2]#tab5
gaps array · 4 items
[0]
asset:data:geo:GSE53757 not downloaded
[1]
asset:data:geo:GSE53757 licence not read
[2]
asset:data:geo:GSE73731 not downloaded
[3]
asset:data:geo:GSE73731 licence not read
analysis object · 4 fields
state
complete
methods array · 1 item
[0] object · 10 fields
id
method-1
family
differential_expression
specific
limma_voom
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
1
band
verbatim
quote
The gene expression levels in ccRCC stages I, II, III, and IV were compared with those in normal tissue using the limma package [33] in R software.
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 · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
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: limma_voom.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 2 items
[0]
GSE53757
[1]
GSE73731
resolved_accessions array · 2 items
[0]
GSE53757
[1]
GSE73731
statements array · 1 item
[0]
All data included in this study are available upon request by contact with the corresponding author.
basis
The paper names GSE53757, GSE73731 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 · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
assets array · 7 items
[0]
source:pmid:32309427
[1]
data:geo:GSE53757
[2]
asset:table:pmid:32309427:1
[3]
asset:table:pmid:32309427:2
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asset:table:pmid:32309427:3
[5]
asset:table:pmid:32309427:4
[6]
asset:table:pmid:32309427:5
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:GSE53757
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
2026-10-31T18:19:20Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
37929
completion_tokens
1600
cached_tokens
784
stages array · 1 item
[0] object · 4 fields
id
extraction
state
complete
reader
MiniMax-M3.1-Flash
provider
minimax
gaps array · 3 items
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review.independent_reader
[1]
review.machine_critique
[2]
review.human_critique
execution object · 5 fields
state
absent
status
not_run
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null
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gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:32309427
type
paper
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pmid:32309427
[1] object · 3 fields
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source:pmid:32309427
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manuscript
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PMID 32309427 full text
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data:geo:GSE53757
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GEO GSE53757
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classification
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pmid:32309427
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pmid:32309427
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source:pmid:32309427
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PMID 32309427 full text
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data:geo:GSE53757
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GEO GSE53757
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agent:corpus-assay-engine
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agent:minimax-reader
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activity-resolve-GSE53757
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data:geo:GSE53757
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agent:corpus-assay-engine
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agent:minimax-reader
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343fb30756ba6ec3
capability_table_fingerprint
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lineage object · 4 fields
parent_id
pmid:32309427
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gaps array · 8 items
[0]
asset:data:geo:GSE53757 licence not read
[1]
asset:data:geo:GSE53757 not downloaded
[2]
asset:data:geo:GSE73731 licence not read
[3]
asset:data:geo:GSE73731 not downloaded
[4]
execution.not_run
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review.human_critique
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99e1195c7d6f
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evidence array · 1 item
[0]
cRCC. First, we analyzed the gene expression microarray data sets: GSE53757 and GSE73731. We divided
order_basis
paper_text_order:606
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assay:1
[1] object · 11 fields
role
analysis
definition_id
differential_expression
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fdr_bh
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dsl_catalogue
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The gene expression levels in ccRCC stages I, II, III, and IV were compared with those in normal tissue using the limma package [33] in R software.
order_basis
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32309427", "kind": "science-record", "revision": 8, "content_hash": "sha256:1c97cab106a6b19d0d6abff09d7c3bbe5933b06ba879b00b2939f0bcf59b7944", "created_at": "2026-11-01T15:40:59Z", "updated_at": "2026-11-01T22:44:46Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Four Pathological Stage-Relevant Genes in Association with Progression and Prognosis in Clear Cell Renal Cell Carcinoma by Integrated Bioinformatics Analysis.", "doi": "10.1155/2020/2137319", "pmid": "32309427", "authors": ["Dengyong Xu", "Yuzi Xu", "Yiming Lv", "Fei Wu", "Yunlong Liu", "Ming Zhu", "Dake Chen", "Bingjun Bai"], "journal": "BioMed research international", "year": 2020, "abstract": "Clear cell renal cell carcinoma (ccRCC) is a major histological subtype of renal cell carcinoma and can be clinically divided into four stages according to the TNM criteria. Identifying clinical stage-related genes is beneficial for improving the early diagnosis and prognosis of ccRCC. By using bioinformatics analysis, we aim to identify clinical stage-relevant genes that are significantly associated with the development of ccRCC. First, we analyzed the gene expression microarray data sets: GSE53757 and GSE73731. We divided these data into five groups by staging information-normal tissue and ccRCC stages I, II, III, and IV-and eventually identified 500 differentially expressed genes (DEGs). To obtain precise stage-relevant genes, we subsequently applied weighted gene coexpression network analysis (WGCNA) to the GSE73731 dataset and KIRC data from The Cancer Genome Atlas (TCGA). Two modules from each dataset were identified to be related to the tumor TNM stage. Several genes with high inner connection inside the modules were considered hub genes. The intersection results between hub genes of key modules and 500 DEGs revealed UBE2C, BUB1B, RRM2, and TPX2 as highly associated with the stage of ccRCC. In addition, the candidate genes were validated at both the RNA expression level and the protein level. Survival analysis also showed that 4 genes were significantly correlated with overall survival. In conclusion, our study affords a deeper understanding of the molecular mechanisms associated with the development of ccRCC and provides potential biomarkers for early diagnosis and individualized treatment for patients at different stages of ccRCC.", "claims": [{"id": "claim-method", "statement": "The gene expression levels in ccRCC stages I, II, III, and IV were compared with those in normal tissue using the limma package [33] in R software.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32309427", "locator": "sections[4] \"2.2. Identification of DEGs\" paragraph 2", "quote": "The gene expression levels in ccRCC stages I, II, III, and IV were compared with those in normal tissue using the limma package [33] in R software."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data included in this study are available upon request by contact with the corresponding author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32309427", "locator": "sections[28] \"Data Availability\" paragraph 2", "quote": "All data included in this study are available upon request by contact with the corresponding author."}], "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:32309427"], "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:GSE53757"], "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:GSE53757"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32309427", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2020/2137319", "sha256": 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