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pmid:32825936

Identification of methylated-differentially expressed genes and pathways in esophageal squamous cell carcinoma.

Liang Sang · Zhanwu Yu · Ang Wang · Hao Li · Xiantong Dai · Liping Sun · Hongxu Liu · Yuan Yuan

Pathology, research and practice · 2020 doi:10.1016/j.prp.2020.153050

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Experiment

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Data

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pmid:32825936
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title
Identification of methylated-differentially expressed genes and pathways in esophageal squamous cell carcinoma.
doi
10.1016/j.prp.2020.153050
pmid
32825936
authors array · 8 items
[0]
Liang Sang
[1]
Zhanwu Yu
[2]
Ang Wang
[3]
Hao Li
[4]
Xiantong Dai
[5]
Liping Sun
[6]
Hongxu Liu
[7]
Yuan Yuan
journal
Pathology, research and practice
year
2020
abstract
Methylation, as an epigenetic modification, can affect gene expression and play a role in the occurrence and development of cancer. This research is devoted to discover methylated-differentially expressed genes (MDEGs) in esophageal squamous cell carcinoma (ESCC) and explore special associated pathways. We downloaded GSE51287 methylation profiles and GSE26886 expression profiles from GEO DataSets, and performed a comprehensive bioinformatics analysis. Totally, 19 hypermethylated, lowly expressed genes (Hyper-LGs) were identified, and involved in regulation of cell proliferation, phosphorus metabolic process and protein kinase activity. Meanwhile, 17 hypomethylated, highly expressed genes (Hypo-HGs) were participated in collagen catabolic process, metallopeptidase and cytokine activity. Pathway analysis determined that Hyper-LGs were enriched in arachidonic acid metabolism pathway, while Hypo-HGs were primarily associated with the cytokine-cytokine receptor interaction pathway. IL 6, MMP3, MMP9, SPP1 were identified as hub genes based on the PPI network that combined 7 ranked methods included in cytoHubba, and verification was performed in human tissues. Our integrated analysis identified many novel genetic lesions in ESCC and provides a crucial molecular foundation to improve our understanding of ESCC. Hub genes, including IL 6, MMP3, MMP9 and SPP1, could be considered for use as aberrant methylation-based biomarkers to facilitate the accurate diagnosis and therapy of ESCC.
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Differential expression between normal and ESCC tissue samples was identified using the online tool GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r/) across experimental conditions in the GEO series. The multiple t-test was used to detect statistically significant genes, and the Benjamin & Hochberg false discovery rate method is selected.
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Differential expression between normal and ESCC tissue samples was identified using the online tool GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r/) across experimental conditions in the GEO series. The multiple t-test was used to detect statistically significant genes, and the Benjamin & Hochberg false discovery rate method is selected.
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The GSE51287 gene methylation microarray data comprise 98 ESCC and 93 normal tissue specimens (platform: GPL9183 Illumina GoldenGate Methylation Cancer Panel I); 9 ESCC and 19 normal squamous epithelial specimens are registered for GSE26886 (platform: GPL[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array).
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The GSE51287 gene methylation microarray data comprise 98 ESCC and 93 normal tissue specimens (platform: GPL9183 Illumina GoldenGate Methylation Cancer Panel I); 9 ESCC and 19 normal squamous epithelial specimens are registered for GSE26886 (platform: GPL[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array).
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The GSE51287 gene methylation microarray data comprise 98 ESCC and 93 normal tissue specimens (platform: GPL9183 Illumina GoldenGate Methylation Cancer Panel I); 9 ESCC and 19 normal squamous epithelial specimens are registered for GSE26886 (platform: GPL[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array).
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sha256:217423467a39a2f8e19e7f7601c8f1feb7df849b3578d901b4e5a57ec2ce9fe3
bytes
280
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[8]/table-wrap[2]#tbl0010
version
null
note
PCR reaction conditions.
structure object · 5 fields
pmcid
PMC7283077
section_index
8
section_title
Verification of hub genes in human tissues
row_count
5
column_count
3
table object · 8 fields
label
Table 2
caption
PCR reaction conditions.
rows array · 5 items
[0] array · 3 items
[0]
[1]
94 °C
[2]
5min
[1] array · 3 items
[0]
40cyc
[1]
94 °C
[2]
20 s
[2] array · 2 items
[0]
55 °C
[1]
20 s
[3] array · 2 items
[0]
72 °C
[1]
30 s
[4] array · 3 items
[0]
[1]
72 °C
[2]
6min
locator
section[8]/table-wrap[2]#tbl0010
[5] object · 16 fields
id
asset:table:pmid:32825936:3
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:787200912a4bf7d5702ce1fabbdd9296202fe447fc0db53c689084aeab1ce968
bytes
537
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[8]/table-wrap[3]#tbl0015
version
null
note
Realtime-PCR primer sequence.
structure object · 5 fields
pmcid
PMC7283077
section_index
8
section_title
Verification of hub genes in human tissues
row_count
11
column_count
3
table object · 8 fields
label
Table 3
caption
Realtime-PCR primer sequence.
rows array · 11 items
[0] array · 2 items
[0]
Name
[1]
Sequence
[1] array · 3 items
[0]
MMP9
[1]
F
[2]
GGGACGCAGACATCGTCATC
[2] array · 2 items
[0]
R
[1]
TCGTCATCGTCGAAATGGGC
[3] array · 3 items
[0]
MMP7
[1]
F
[2]
GAGTGAGCTACAGTGGGAACA
[4] array · 2 items
[0]
R
[1]
CTATGACGCGGGAGTTTAACAT
[5] array · 3 items
[0]
MMP3
[1]
F
[2]
CGGTTCCGCCTGTCTCAAG
[6] array · 2 items
[0]
R
[1]
CGCCAAAAGTGCCTGTCTT
[7] array · 3 items
[0]
SPP1
[1]
F
[2]
CTCCATTGACTCGAACGACTC
[8] array · 2 items
[0]
R
[1]
CAGGTCTGCGAAACTTCTTAGAT
[9] array · 3 items
[0]
IL-6
[1]
F
[2]
ACTCACCTCTTCAGAACGAATTG
[10] array · 2 items
[0]
R
[1]
CCATCTTTGGAAGGTTCAGGTTG
locator
section[8]/table-wrap[3]#tbl0015
[6] object · 16 fields
id
asset:table:pmid:32825936:4
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:4d34f595ffbe3e3debe31172ace6cbcab37ae409499a5bc5d994892d46488e29
bytes
309
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[8]/table-wrap[4]#tbl0020
version
null
note
Realtime-PCR reaction conditions.
structure object · 5 fields
pmcid
PMC7283077
section_index
8
section_title
Verification of hub genes in human tissues
row_count
6
column_count
3
table object · 8 fields
label
Table 4
caption
Realtime-PCR reaction conditions.
rows array · 6 items
[0] array · 3 items
[0]
[1]
95 °C
[2]
30 s
[1] array · 3 items
[0]
40cyc
[1]
95 °C
[2]
10 s
[2] array · 2 items
[0]
56 °C
[1]
20 s
[3] array · 2 items
[0]
72 °C
[1]
30 s
[4] array · 2 items
[0]
[1]
melting curve
[5] array · 3 items
[0]
[1]
4 °C
[2]
Hold
locator
section[8]/table-wrap[4]#tbl0020
[7] object · 16 fields
id
asset:table:pmid:32825936:5
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:bf0a012589fe348f9069937b8cb1b1121bec322bfe2a4e246734ff97bc42e435
bytes
2669
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[11]/table-wrap[1]#tbl0025
version
null
note
GO enrichment analysis of MDEGs related to ESCC.
structure object · 5 fields
pmcid
PMC7283077
section_index
11
section_title
GO functional enrichment analysis
row_count
29
column_count
6
table object · 8 fields
label
Table 5
caption
GO enrichment analysis of MDEGs related to ESCC.
rows array · 29 items
[0] array · 5 items
[0]
Category
[1]
Term
[2]
Count
[3]
%
[4]
PValue
[1] array · 6 items
[0]
Hyper-LGs
[1]
GOTERM_BP_FAT
[2]
GO:0006468∼protein amino acid phosphorylation
[3]
6
[4]
31.58
[5]
1.44E-03
[2] array · 6 items
[0]
[1]
GOTERM_BP_FAT
[2]
GO:0042127∼regulation of cell proliferation
[3]
6
[4]
31.58
[5]
2.99E-03
[3] array · 6 items
[0]
[1]
GOTERM_BP_FAT
[2]
GO:0016310∼phosphorylation
[3]
6
[4]
31.58
[5]
3.21E-03
[4] array · 6 items
[0]
[1]
GOTERM_BP_FAT
[2]
GO:0046777∼protein amino acid autophosphorylation
[3]
3
[4]
15.79
[5]
5.59E-03
[5] array · 6 items
[0]
[1]
GOTERM_BP_FAT
[2]
GO:0006793∼phosphorus metabolic process
[3]
6
[4]
31.58
[5]
7.41E-03
[6] array · 6 items
[0]
[1]
GOTERM_CC_FAT
[2]
GO:0012505∼endomembrane system
[3]
4
[4]
21.05
[5]
4.12E-02
[7] array · 6 items
[0]
[1]
GOTERM_CC_FAT
[2]
GO:0044459∼plasma membrane part
[3]
6
[4]
31.58
[5]
5.79E-02
[8] array · 6 items
[0]
[1]
GOTERM_MF_FAT
[2]
GO:0004672∼protein kinase activity
[3]
6
[4]
31.58
[5]
8.44E-04
[9] array · 6 items
[0]
[1]
GOTERM_MF_FAT
[2]
GO:0004713∼protein tyrosine kinase activity
[3]
4
[4]
21.05
[5]
1.22E-03
[10] array · 6 items
[0]
[1]
GOTERM_MF_FAT
[2]
GO:0004714∼transmembrane receptor protein tyrosine kinase activity
[3]
3
[4]
15.79
[5]
3.39E-03
[11] array · 6 items
[0]
[1]
GOTERM_MF_FAT
[2]
GO:0005021∼vascular endothelial growth factor receptor activity
[3]
2
[4]
10.53
[5]
1.04E-02
[12] array · 6 items
[0]
[1]
GOTERM_MF_FAT
[2]
GO:0005524∼ATP binding
[3]
6
[4]
31.58
[5]
3.64E-02
[13] array · 1 item
[0]
[14] array · 6 items
[0]
Hypo-HGs
[1]
GOTERM_BP_FAT
[2]
GO:0030574∼collagen catabolic process
[3]
4
[4]
22.22
[5]
1.53E-06
[15] array · 6 items
[0]
[1]
GOTERM_BP_FAT
[2]
GO:0044243∼multicellular organismal catabolic process
[3]
4
[4]
22.22
[5]
3.47E-06
[16] array · 6 items
[0]
[1]
GOTERM_BP_FAT
[2]
GO:0032963∼collagen metabolic process
[3]
4
[4]
22.22
[5]
4.37E-06
[17] array · 6 items
[0]
[1]
GOTERM_BP_FAT
[2]
GO:0044259∼multicellular organismal macromolecule metabolic process
[3]
4
[4]
22.22
[5]
5.98E-06
[18] array · 6 items
[0]
[1]
GOTERM_BP_FAT
[2]
GO:0044236∼multicellular organismal metabolic process
[3]
4
[4]
22.22
[5]
1.03E-05
[19] array · 6 items
[0]
[1]
GOTERM_CC_FAT
[2]
GO:0044421∼extracellular region part
[3]
10
[4]
55.56
[5]
1.03E-06
[20] array · 6 items
[0]
[1]
GOTERM_CC_FAT
[2]
GO:0005615∼extracellular space
[3]
9
[4]
50.00
[5]
1.03E-06
[21] array · 6 items
[0]
[1]
GOTERM_CC_FAT
[2]
GO:0005576∼extracellular region
[3]
10
[4]
55.56
[5]
4.21E-04
[22] array · 6 items
[0]
[1]
GOTERM_CC_FAT
[2]
GO:0005578∼proteinaceous extracellular matrix
[3]
5
[4]
27.78
[5]
7.09E-04
[23] array · 6 items
[0]
[1]
GOTERM_CC_FAT
[2]
GO:0031012∼extracellular matrix
[3]
5
[4]
27.78
[5]
9.39E-04
[24] array · 6 items
[0]
[1]
GOTERM_MF_FAT
[2]
GO:0004222∼metalloendopeptidase activity
[3]
4
[4]
22.22
[5]
2.59E-04
[25] array · 6 items
[0]
[1]
GOTERM_MF_FAT
[2]
GO:0008237∼metallopeptidase activity
[3]
4
[4]
22.22
[5]
1.35E-03
[26] array · 6 items
[0]
[1]
GOTERM_MF_FAT
[2]
GO:0004175∼endopeptidase activity
[3]
4
[4]
22.22
[5]
1.01E-02
[27] array · 6 items
[0]
[1]
GOTERM_MF_FAT
[2]
GO:0005509∼calcium ion binding
[3]
5
[4]
27.78
[5]
2.29E-02
[28] array · 6 items
[0]
[1]
GOTERM_MF_FAT
[2]
GO:0005125∼cytokine activity
[3]
3
[4]
16.67
[5]
2.35E-02
locator
section[11]/table-wrap[1]#tbl0025
[8] object · 16 fields
id
asset:table:pmid:32825936:6
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:544c305ab19b62f3ae6ccc6fc15a798ea3c7e4e7e1464b78ce70a0ad7556d01f
bytes
529
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[12]/table-wrap[1]#tbl0030
version
null
note
KEGG pathway analysis of MDEGs related to ESCC.
structure object · 5 fields
pmcid
PMC7283077
section_index
12
section_title
KEGG pathway analysis
row_count
5
column_count
6
table object · 8 fields
label
Table 6
caption
KEGG pathway analysis of MDEGs related to ESCC.
rows array · 5 items
[0] array · 5 items
[0]
Category
[1]
Term
[2]
Count
[3]
%
[4]
PValue
[1] array · 6 items
[0]
Hyper-LGs
[1]
KEGG_PATHWAY
[2]
hsa00590:Arachidonic acid metabolism
[3]
2
[4]
10.53
[5]
9.49E-02
[2] array · 1 item
[0]
[3] array · 6 items
[0]
Hypo-HGs
[1]
KEGG_PATHWAY
[2]
hsa04620:Toll-like receptor signaling pathway
[3]
3
[4]
16.67
[5]
1.58E-02
[4] array · 6 items
[0]
[1]
KEGG_PATHWAY
[2]
hsa04060:Cytokine-cytokine receptor interaction
[3]
3
[4]
16.67
[5]
9.06E-02
locator
section[12]/table-wrap[1]#tbl0030
[9] object · 16 fields
id
asset:table:pmid:32825936:7
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:83cbc1cf95ec13a6228f8f9126a3164b7ef99a497cbd900c991df71c89f7985a
bytes
574
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[13]/table-wrap[1]#tbl0035
version
null
note
Hub genes for Hypo-HGs ranked in cytoHubba.
structure object · 5 fields
pmcid
PMC7283077
section_index
13
section_title
PPI network construction and cytoHubba analysis
row_count
7
column_count
8
table object · 8 fields
label
Table 7
caption
Hub genes for Hypo-HGs ranked in cytoHubba.
rows array · 7 items
[0] array · 2 items
[0]
gene symbols
[1]
Ranking methods in cytoHubba
[1] array · 7 items
[0]
MCC
[1]
DMNC
[2]
MNC
[3]
Degree
[4]
EPC
[5]
Closeness
[6]
Radiality
[2] array · 8 items
[0]
IL6
[1]
1572
[2]
0.42
[3]
13
[4]
13
[5]
4.49
[6]
13.50
[7]
3.21
[3] array · 8 items
[0]
MMP9
[1]
1568
[2]
0.53
[3]
11
[4]
11
[5]
4.26
[6]
12.33
[7]
3.00
[4] array · 8 items
[0]
MMP3
[1]
1560
[2]
0.67
[3]
9
[4]
9
[5]
4.05
[6]
11.33
[7]
2.86
[5] array · 8 items
[0]
MMP7
[1]
1560
[2]
0.67
[3]
9
[4]
9
[5]
3.99
[6]
11.33
[7]
2.86
[6] array · 8 items
[0]
SPP1
[1]
1448
[2]
0.54
[3]
10
[4]
10
[5]
4.15
[6]
11.83
[7]
2.93
locator
section[13]/table-wrap[1]#tbl0035
[10] object · 16 fields
id
asset:table:pmid:32825936:8
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:d3261b418ff28e793feebeb62583aa476c46bd245f2daeae558737855ca1233b
bytes
1073
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[15]/table-wrap[1]#tbl0040
version
null
note
Human tissue verification for hub genes.
structure object · 5 fields
pmcid
PMC7283077
section_index
15
section_title
Verification in human tissues
row_count
17
column_count
5
table object · 8 fields
label
Table 8
caption
Human tissue verification for hub genes.
rows array · 17 items
[0] array · 3 items
[0]
gene
[1]
mRNA expression
[2]
Methylation
[1] array · 4 items
[0]
Median(25 %,75 %)a
[1]
P value
[2]
Median(25 %,75 %)
[3]
P value
[2] array · 5 items
[0]
MMP3
[1]
[2]
0.290
[3]
[4]
0.885
[3] array · 5 items
[0]
Tumor
[1]
3.700(4.020, 2.809)
[2]
[3]
0.784(0.695, 0.825)
[4]
[4] array · 5 items
[0]
Non-tumor
[1]
4.326(5.601, 2.996)
[2]
[3]
0.786(0.753, 0.870)
[4]
[5] array · 5 items
[0]
MMP9
[1]
[2]
0.096
[3]
[4]
0.131
[6] array · 5 items
[0]
Tumor
[1]
2.757(3.192, 2.659)
[2]
[3]
0.191(0.120, 0.539)
[4]
[7] array · 5 items
[0]
Non-tumor
[1]
3.265(3.574, 2.851)
[2]
[3]
0.455(0.407, 0.546)
[4]
[8] array · 5 items
[0]
MMP7
[1]
[2]
0.510
[3]
[4]
0.261
[9] array · 5 items
[0]
Tumor
[1]
3.796(4.243, 3.219)
[2]
[3]
0.918(0.894, 0.959)
[4]
[10] array · 5 items
[0]
Non-tumor
[1]
3.016(4.999, 2.363)
[2]
[3]
0.934(0.918, 0.951)
[4]
[11] array · 5 items
[0]
SPP1
[1]
[2]
0.033
[3]
[4]
0.108
[12] array · 5 items
[0]
Tumor
[1]
2.411(3.244, 2.297)
[2]
[3]
0.786(0.722, 0.866)
[4]
[13] array · 5 items
[0]
Non-tumor
[1]
3.552(4.330, 3.315)
[2]
[3]
0.849(0.824, 0.882)
[4]
[14] array · 5 items
[0]
IL-6
[1]
[2]
0.345
[3]
[4]
0.520
[15] array · 5 items
[0]
Tumor
[1]
4.083(4.533, 3.779)
[2]
[3]
0.847(0.834, 0.910)
[4]
[16] array · 5 items
[0]
Non-tumor
[1]
4.608(5.253, 3.883)
[2]
[3]
0.892(0.834, 0.932)
[4]
locator
section[15]/table-wrap[1]#tbl0040
gaps array · 4 items
[0]
asset:data:geo:GSE26886 not downloaded
[1]
asset:data:geo:GSE26886 licence not read
[2]
asset:data:geo:GSE51287 not downloaded
[3]
asset:data:geo:GSE51287 licence not read
analysis object · 4 fields
state
partial
methods array · 2 items
[0] object · 10 fields
id
method-1
family
network_analysis
specific
ppi_network
label
Network / pathway analysis
dsl_operations array · 3 items
[0]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
edge_list
evidence object · 3 fields
score
0.7
band
medium
quote
PPI
[1] object · 10 fields
id
method-2
family
null
specific
null
label
Multiple t-test with Benjamin–Hochberg false discovery rate adjustment, applied using GEO2R
dsl_operations array · 0 items
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 0 items
evidence object · 3 fields
score
1
band
verbatim
quote
Differential expression between normal and ESCC tissue samples was identified using the online tool GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r/) across experimental conditions in the GEO series. The multiple t-test was used to detect statistically significant genes, and the Benjamin & Hochberg false discovery rate method is selected.
targets array · 0 items
gaps array · 1 item
[0]
method.reader_named_unmapped
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]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
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: ppi_network.
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]
GSE51287
[1]
GSE26886
resolved_accessions array · 2 items
[0]
GSE51287
[1]
GSE26886
statements array · 1 item
[0]
The GSE51287 gene methylation microarray data comprise 98 ESCC and 93 normal tissue specimens (platform: GPL9183 Illumina GoldenGate Methylation Cancer Panel I); 9 ESCC and 19 normal squamous epithelial specimens are registered for GSE26886 (platform: GPL[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array).
basis
The paper names GSE51287, GSE26886 in Gene Expression Omnibus (GEO) DataSets 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]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
assets array · 10 items
[0]
source:pmid:32825936
[1]
data:geo:GSE26886
[2]
asset:table:pmid:32825936:1
[3]
asset:table:pmid:32825936:2
[4]
asset:table:pmid:32825936:3
[5]
asset:table:pmid:32825936:4
[6]
asset:table:pmid:32825936:5
[7]
asset:table:pmid:32825936:6
[8]
asset:table:pmid:32825936:7
[9]
asset:table:pmid:32825936:8
steps array · 1 item
[0]
run_analysis
must_build object · 5 fields
dsl_operations array · 0 items
converters array · 0 items
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32825936", "kind": "science-record", "revision": 6, "content_hash": "sha256:d4b549f6722d4f681ea8ac3889d6680c6bcddd736813fd092b49668c4dc4c652", "created_at": "2026-11-01T15:41:08Z", "updated_at": "2026-11-01T22:02:04Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of methylated-differentially expressed genes and pathways in esophageal squamous cell carcinoma.", "doi": "10.1016/j.prp.2020.153050", "pmid": "32825936", "authors": ["Liang Sang", "Zhanwu Yu", "Ang Wang", "Hao Li", "Xiantong Dai", "Liping Sun", "Hongxu Liu", "Yuan Yuan"], "journal": "Pathology, research and practice", "year": 2020, "abstract": "Methylation, as an epigenetic modification, can affect gene expression and play a role in the occurrence and development of cancer. This research is devoted to discover methylated-differentially expressed genes (MDEGs) in esophageal squamous cell carcinoma (ESCC) and explore special associated pathways. We downloaded GSE51287 methylation profiles and GSE26886 expression profiles from GEO DataSets, and performed a comprehensive bioinformatics analysis. Totally, 19 hypermethylated, lowly expressed genes (Hyper-LGs) were identified, and involved in regulation of cell proliferation, phosphorus metabolic process and protein kinase activity. Meanwhile, 17 hypomethylated, highly expressed genes (Hypo-HGs) were participated in collagen catabolic process, metallopeptidase and cytokine activity. Pathway analysis determined that Hyper-LGs were enriched in arachidonic acid metabolism pathway, while Hypo-HGs were primarily associated with the cytokine-cytokine receptor interaction pathway. IL 6, MMP3, MMP9, SPP1 were identified as hub genes based on the PPI network that combined 7 ranked methods included in cytoHubba, and verification was performed in human tissues. Our integrated analysis identified many novel genetic lesions in ESCC and provides a crucial molecular foundation to improve our understanding of ESCC. Hub genes, including IL 6, MMP3, MMP9 and SPP1, could be considered for use as aberrant methylation-based biomarkers to facilitate the accurate diagnosis and therapy of ESCC.", "claims": [{"id": "claim-method", "statement": "Differential expression between normal and ESCC tissue samples was identified using the online tool GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r/) across experimental conditions in the GEO series. The multiple t-test was used to detect statistically significant genes, and the Benjamin & Hochberg false discovery rate method is selected.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32825936", "locator": "sections[4] \"Data process\" paragraph 2", "quote": "Differential expression between normal and ESCC tissue samples was identified using the online tool GEO2R (http://www.ncbi.nlm.nih.gov/geo/geo2r/) across experimental conditions in the GEO series. The multiple t-test was used to detect statistically significant genes, and the Benjamin & Hochberg false discovery rate method is selected."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GSE51287 gene methylation microarray data comprise 98 ESCC and 93 normal tissue specimens (platform: GPL9183 Illumina GoldenGate Methylation Cancer Panel I); 9 ESCC and 19 normal squamous epithelial specimens are registered for GSE26886 (platform: GPL[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32825936", "locator": "sections[3] \"Microarray data\" paragraph 2", "quote": "The GSE51287 gene methylation microarray data comprise 98 ESCC and 93 normal tissue specimens (platform: GPL9183 Illumina GoldenGate Methylation Cancer Panel I); 9 ESCC and 19 normal squamous epithelial specimens are registered for GSE26886 (platform: GPL[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array)."}], "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:32825936"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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The multiple t-test was used to detect statistically significant genes, and the Benjamin & Hochberg false discovery rate method is selected."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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