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pmid:29201983

Data on novel DNA methylation changes induced by valproic acid in human hepatocytes.

JarnoEJ Wolters · SimoneGJ van Breda · SandraM Claessen · TheoMCM de Kok · JosCS Kleinjans

Data in brief · 2018 doi:10.1016/j.dib.2017.11.031

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complete

Experiment

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Data

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Analysis

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:29201983
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2026-11-01T15:40:30Z
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title
Data on novel DNA methylation changes induced by valproic acid in human hepatocytes.
doi
10.1016/j.dib.2017.11.031
pmid
29201983
authors array · 5 items
[0]
JarnoEJ Wolters
[1]
SimoneGJ van Breda
[2]
SandraM Claessen
[3]
TheoMCM de Kok
[4]
JosCS Kleinjans
journal
Data in brief
year
2018
abstract
Valproic acid (VPA) is a widely prescribed antiepileptic drug in the world. Despite its pharmacological importance, it may cause liver toxicity and steatosis. However the exact mechanism of the steatosis formation is unknown. The data presented in this DIB publication is used to further investigate the VPA-induced mechanisms of steatosis by analyzing changes in patterns of methylation. Therefore, primary human hepatocytes (PHHs) were exposed to VPA at a concentration which was shown to cause steatosis without inducing overt cytotoxicity. VPA was administered for 5 days daily to PHHs. Furthermore, after 5 days VPA-treatment parts of the PHHs were followed for a 3 days washout. Differentially methylated DNA regions (DMRs) were identified by using the 'Methylated DNA Immuno-Precipitation - sequencing' (MeDIP-seq) method. The data presented in this DIB demonstrate induced steatosis pathways by all DMRs during VPA-treatment, covering interesting drug-induced steatosis genes (persistent DMRs upon terminating VPA treatment and the EP300 network). This was illustrated in our associated article (Wolters et al., 2017) [1]. MeDIP-seq raw data are available on ArrayExpress (accession number: E-MTAB-4437).
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Statistical analysis was performed applying the default parameters of MEDIPS, using the edgeR module, an empirical analysis of digital gene expression data in R that uses Bayes estimation and exact tests based on the negative binomial distribution [8].
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sections[15] "MeDIP-Seq analysis" paragraph 2
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Statistical analysis was performed applying the default parameters of MEDIPS, using the edgeR module, an empirical analysis of digital gene expression data in R that uses Bayes estimation and exact tests based on the negative binomial distribution [8].
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MeDIP-seq raw data are available on ArrayExpress (accession number: E-MTAB-4437).
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MeDIP-seq raw data are available on ArrayExpress (accession number: E-MTAB-4437).
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The study identified DMRs using MEDIPS with edgeR, negative-binomial exact tests, and TMM normalization, and the raw MeDIP-seq source data are available through ArrayExpress under accession E-MTAB-4437.
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The MEDIPS package (version 1.16.0, Bioconductor) was used for the analysis of the MeDIP-seq data [4], [5], [6].
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sections[15] "MeDIP-Seq analysis" paragraph 2
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Statistical analysis was performed applying the default parameters of MEDIPS, using the edgeR module, an empirical analysis of digital gene expression data in R that uses Bayes estimation and exact tests based on the negative binomial distribution [8].
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Notably, raw count data was normalized using the weighted trimmed mean of M-values (TMM-normalization).
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The study identified DMRs using MEDIPS with edgeR, negative-binomial exact tests, and TMM normalization, and the raw MeDIP-seq source data are available through ArrayExpress under accession E-MTAB-4437.
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Department of Toxicogenomics, Maastricht University, the Netherlands
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The treated samples were corrected for time-matched vehicle controls.
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The persistent changes were identified by determining DNA methylation similarities between samples of 5 days daily VPA-treatment and samples of 3 days washout upon the 5 days daily VPA-treatment
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Department of Toxicogenomics, Maastricht University, the Netherlands
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Names and functions of the 20 persistently hypermethylated DMRs annotated to 15 unique Entrez Genes (A) and the 11 hypomethylated DMRs annotated to 9 unique Entrez Genes (B) of the MEDIP-seq analysis after the exposure of PHHs for 5 days daily to VPA followed by 3 days washout. PHHs, primary human hepatocytes; VPA, valproic acid; DMRs, differentially methylated DNA regions.
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Table 1
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Names and functions of the 20 persistently hypermethylated DMRs annotated to 15 unique Entrez Genes (A) and the 11 hypomethylated DMRs annotated to 9 unique Entrez Genes (B) of the MEDIP-seq analysis after the exposure of PHHs for 5 days daily to VPA followed by 3 days washout. PHHs, primary human hepatocytes; VPA, valproic acid; DMRs, differentially methylated DNA regions.
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[0] array · 1 item
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A) 20 persistently hypermethylated DMRs annotated to 15 unique Entrez Genes
[1] array · 4 items
[0]
Entrez Gene ID
[1]
Gene Symbol
[2]
Gene Name
[3]
NCBI Gene Function
[2] array · 4 items
[0]
114
[1]
ADCY8
[2]
adenylate cyclase 8 (brain)
[3]
membrane bound enzyme that catalyses the formation of cyclic AMP from ATP
[3] array · 4 items
[0]
5099
[1]
PCDH7
[2]
protocadherin 7
[3]
The gene product is an integral membrane protein that is thought to function in cell-cell recognition and adhesion
[4] array · 4 items
[0]
7625
[1]
ZNF74
[2]
zinc finger protein 74
[3]
–
[5] array · 4 items
[0]
23078
[1]
VWA8
[2]
von Willebrand factor A domain containing 8
[3]
–
[6] array · 4 items
[0]
55591
[1]
VEZT
[2]
vezatin, adherens junctions transmembrane protein
[3]
This gene encodes a transmembrane protein which has been localized to adherens junctions and shown to bind to myosin VIIA
[7] array · 4 items
[0]
57521
[1]
RPTOR
[2]
regulatory associated protein of MTOR, complex 1
[3]
encodes a component of a signaling pathway that regulates cell growth in response to nutrient and insulin levels
[8] array · 4 items
[0]
79755
[1]
ZNF750
[2]
zinc finger protein 750
[3]
This gene encodes a protein with a nuclear localization site and a C2H2 zinc finger domain. Mutations in this gene have been associated with seborrhea-like dermatitis with psoriasiform elements.
[9] array · 4 items
[0]
80757
[1]
TMEM121
[2]
transmembrane protein 121
[3]
–
[10] array · 4 items
[0]
114784
[1]
CSMD2
[2]
CUB and Sushi multiple domains 2
[3]
–
[11] array · 4 items
[0]
122706
[1]
PSMB11
[2]
proteasome (prosome, macropain) subunit, beta type, 11
[3]
Proteasomes generate peptides that are presented by major histocompatibility complex (MHC) I molecules to other cells of the immune system.
[12] array · 4 items
[0]
254827
[1]
NAALADL2
[2]
N-acetylated alpha-linked acidic dipeptidase-like 2
[3]
–
[13] array · 4 items
[0]
338707
[1]
B4GALNT4
[2]
beta-1,4-N-acetyl-galactosaminyl transferase 4
[3]
–
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[0]
388228
[1]
SBK1
[2]
SH3 domain binding kinase 1
[3]
–
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[0]
440073
[1]
IQSEC. 3
[2]
IQ motif and Sec. 7 domain 3
[3]
–
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[0]
100507290
[1]
ZNF865
[2]
zinc finger protein 865
[3]
–
[17] array · 1 item
[0]
[18] array · 1 item
[0]
B) 11 persistently hypomethylated DMRs annotated to 9 unique Entrez Genes
[19] array · 1 item
[0]
[20] array · 4 items
[0]
Entrez Gene ID
[1]
Gene Symbol
[2]
Gene Name
[3]
NCBI Gene Function
[21] array · 1 item
[0]
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[0]
290
[1]
ANPEP
[2]
alanyl (membrane) aminopeptidase
[3]
Aminopeptidase N is located in the small-intestinal and renal microvillar membrane, and also in other plasma membranes. In the small intestine aminopeptidase N plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases.
[23] array · 4 items
[0]
29982
[1]
NRBF2
[2]
nuclear receptor binding factor 2
[3]
–
[24] array · 4 items
[0]
136051
[1]
ZNF786
[2]
zinc finger protein 786
[3]
–
[25] array · 4 items
[0]
414763
[1]
BMS1P18
[2]
BMS1 ribosome biogenesis factor pseudogene 18
[3]
–
[26] array · 4 items
[0]
643955
[1]
ZNF733P
[2]
zinc finger protein 733, pseudogene
[3]
–
[27] array · 4 items
[0]
646096
[1]
CHEK2P2
[2]
checkpoint kinase 2 pseudogene 2
[3]
–
[28] array · 4 items
[0]
647121
[1]
EMBP1
[2]
embigin pseudogene 1
[3]
–
[29] array · 4 items
[0]
100101266
[1]
HAVCR1P1
[2]
hepatitis A virus cellular receptor 1 pseudogene 1
[3]
–
[30] array · 4 items
[0]
101927554
[1]
LINC01250
[2]
long intergenic non-protein coding RNA 1250
[3]
–
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The ‘enriched pathway-based sets’ from the HOMER annotated genes of the 3006 hypermethylated DMRs and the 3077 hypomethylated DMRs after the exposure of PHHs for 5 days daily to VPA. PHHs, primary human hepatocytes; VPA, valproic acid; DMRs, differentially methylated DNA regions.
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The ‘enriched pathway-based sets’ from the HOMER annotated genes of the 3006 hypermethylated DMRs and the 3077 hypomethylated DMRs after the exposure of PHHs for 5 days daily to VPA. PHHs, primary human hepatocytes; VPA, valproic acid; DMRs, differentially methylated DNA regions.
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[0] array · 6 items
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Pathway name
[1]
Set size
[2]
Candidates, contained
[3]
p-value
[4]
q-value
[5]
Pathway source
[1] array · 6 items
[0]
Developmental Biology
[1]
586
[2]
129 (22.0%)
[3]
3.23E-10
[4]
8.02E-07
[5]
Reactome
[2] array · 6 items
[0]
Axon guidance
[1]
459
[2]
101 (22.0%)
[3]
3.06E-08
[4]
3.81E-05
[5]
Reactome
[3] array · 6 items
[0]
Wnt signaling pathway - Homo sapiens (human)
[1]
140
[2]
36 (25.7%)
[3]
3.17E-05
[4]
0.0262
[5]
KEGG
[4] array · 6 items
[0]
Axon guidance - Homo sapiens (human)
[1]
127
[2]
33 (26.0%)
[3]
5.33E-05
[4]
0.0331
[5]
KEGG
[5] array · 6 items
[0]
Signalling by NGF
[1]
386
[2]
76 (19.7%)
[3]
9.86E-05
[4]
0.0447
[5]
Reactome
[6] array · 6 items
[0]
Signaling by SCF-KIT
[1]
264
[2]
56 (21.2%)
[3]
0.000108
[4]
0.0447
[5]
Reactome
[7] array · 6 items
[0]
Hippo signaling pathway - Homo sapiens (human)
[1]
154
[2]
36 (23.4%)
[3]
0.000257
[4]
0.0914
[5]
KEGG
[8] array · 6 items
[0]
Diseases of signal transduction
[1]
180
[2]
40 (22.2%)
[3]
0.000373
[4]
0.097
[5]
Reactome
[9] array · 6 items
[0]
Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
[1]
20
[2]
9 (45.0%)
[3]
0.00044
[4]
0.097
[5]
Reactome
[10] array · 6 items
[0]
Oxytocin signaling pathway - Homo sapiens (human)
[1]
159
[2]
36 (22.6%)
[3]
0.000494
[4]
0.097
[5]
KEGG
[11] array · 6 items
[0]
BMP2 signaling TGF-beta MV
[1]
56
[2]
17 (30.4%)
[3]
0.000501
[4]
0.097
[5]
INOH
[12] array · 6 items
[0]
Fc gamma R-mediated phagocytosis - Homo sapiens (human)
[1]
92
[2]
24 (26.1%)
[3]
0.000502
[4]
0.097
[5]
KEGG
[13] array · 6 items
[0]
effects of calcineurin in keratinocyte differentiation
[1]
13
[2]
7 (53.8%)
[3]
0.000508
[4]
0.097
[5]
BioCarta
[14] array · 6 items
[0]
NOTCH1 Intracellular Domain Regulates Transcription
[1]
47
[2]
15 (31.9%)
[3]
0.000587
[4]
0.104
[5]
Reactome
[15] array · 6 items
[0]
Calcium signaling pathway - Homo sapiens (human)
[1]
180
[2]
39 (21.7%)
[3]
0.000741
[4]
0.118
[5]
KEGG
[16] array · 6 items
[0]
Signaling by ERBB4
[1]
263
[2]
52 (19.8%)
[3]
0.00107
[4]
0.118
[5]
Reactome
[17] array · 6 items
[0]
Signaling by PDGF
[1]
301
[2]
58 (19.3%)
[3]
0.0011
[4]
0.118
[5]
Reactome
[18] array · 6 items
[0]
Signaling by FGFR3
[1]
270
[2]
53 (19.6%)
[3]
0.00114
[4]
0.118
[5]
Reactome
[19] array · 6 items
[0]
Signaling by FGFR4
[1]
270
[2]
53 (19.6%)
[3]
0.00114
[4]
0.118
[5]
Reactome
[20] array · 6 items
[0]
Signaling by FGFR1
[1]
271
[2]
53 (19.6%)
[3]
0.00125
[4]
0.118
[5]
Reactome
[21] array · 6 items
[0]
Extrinsic Pathway of Fibrin Clot Formation
[1]
5
[2]
4 (80.0%)
[3]
0.00126
[4]
0.118
[5]
Reactome
[22] array · 6 items
[0]
G alpha (12/13) signalling events
[1]
76
[2]
20 (26.3%)
[3]
0.00127
[4]
0.118
[5]
Reactome
[23] array · 6 items
[0]
alk in cardiac myocytes
[1]
27
[2]
10 (37.0%)
[3]
0.00134
[4]
0.118
[5]
BioCarta
[24] array · 6 items
[0]
TGF-beta super family signaling pathway canonical
[1]
115
[2]
27 (23.5%)
[3]
0.00135
[4]
0.118
[5]
INOH
[25] array · 6 items
[0]
nuclear receptors coordinate the activities of chromatin remodeling complexes and coactivators to facilitate initiation of transcription in carcinoma cells
[1]
8
[2]
5 (62.5%)
[3]
0.00145
[4]
0.118
[5]
BioCarta
[26] array · 6 items
[0]
Signaling by FGFR2
[1]
273
[2]
53 (19.4%)
[3]
0.00148
[4]
0.118
[5]
Reactome
[27] array · 6 items
[0]
Interleukin-3, 5 and GM-CSF signaling
[1]
211
[2]
43 (20.4%)
[3]
0.00152
[4]
0.118
[5]
Reactome
[28] array · 6 items
[0]
Downstream signaling of activated FGFR2
[1]
267
[2]
52 (19.5%)
[3]
0.00152
[4]
0.118
[5]
Reactome
[29] array · 6 items
[0]
Downstream signaling of activated FGFR1
[1]
267
[2]
52 (19.5%)
[3]
0.00152
[4]
0.118
[5]
Reactome
[30] array · 6 items
[0]
Downstream signaling of activated FGFR3
[1]
267
[2]
52 (19.5%)
[3]
0.00152
[4]
0.118
[5]
Reactome
[31] array · 6 items
[0]
Downstream signaling of activated FGFR4
[1]
267
[2]
52 (19.5%)
[3]
0.00152
[4]
0.118
[5]
Reactome
[32] array · 6 items
[0]
Signaling by FGFR
[1]
274
[2]
53 (19.3%)
[3]
0.00161
[4]
0.118
[5]
Reactome
[33] array · 6 items
[0]
Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human)
[1]
83
[2]
21 (25.3%)
[3]
0.00167
[4]
0.118
[5]
KEGG
[34] array · 6 items
[0]
Signaling by Insulin receptor
[1]
262
[2]
51 (19.5%)
[3]
0.0017
[4]
0.118
[5]
Reactome
[35] array · 6 items
[0]
Androgen receptor signaling pathway
[1]
89
[2]
22 (24.7%)
[3]
0.00181
[4]
0.118
[5]
Wikipathways
[36] array · 6 items
[0]
Signaling by NOTCH1
[1]
73
[2]
19 (26.0%)
[3]
0.00191
[4]
0.118
[5]
Reactome
[37] array · 6 items
[0]
Ectoderm Differentiation
[1]
141
[2]
31 (22.0%)
[3]
0.00194
[4]
0.118
[5]
Wikipathways
[38] array · 6 items
[0]
Signaling by ERBB2
[1]
277
[2]
53 (19.1%)
[3]
0.00206
[4]
0.118
[5]
Reactome
[39] array · 6 items
[0]
Interleukin-2 signaling
[1]
202
[2]
41 (20.3%)
[3]
0.00209
[4]
0.118
[5]
Reactome
[40] array · 6 items
[0]
HTLV-I infection - Homo sapiens (human)
[1]
259
[2]
50 (19.3%)
[3]
0.00224
[4]
0.118
[5]
KEGG
[41] array · 6 items
[0]
Arrhythmogenic Right Ventricular Cardiomyopathy
[1]
74
[2]
19 (25.7%)
[3]
0.00227
[4]
0.118
[5]
Wikipathways
[42] array · 6 items
[0]
Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human)
[1]
74
[2]
19 (25.7%)
[3]
0.00227
[4]
0.118
[5]
KEGG
[43] array · 6 items
[0]
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
[1]
53
[2]
15 (28.3%)
[3]
0.0023
[4]
0.118
[5]
Reactome
[44] array · 6 items
[0]
Constitutive Signaling by NOTCH1 PEST Domain Mutants
[1]
53
[2]
15 (28.3%)
[3]
0.0023
[4]
0.118
[5]
Reactome
[45] array · 6 items
[0]
Signaling by NOTCH1 PEST Domain Mutants in Cancer
[1]
53
[2]
15 (28.3%)
[3]
0.0023
[4]
0.118
[5]
Reactome
[46] array · 6 items
[0]
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer
[1]
53
[2]
15 (28.3%)
[3]
0.0023
[4]
0.118
[5]
Reactome
[47] array · 6 items
[0]
Signaling by NOTCH1 in Cancer
[1]
53
[2]
15 (28.3%)
[3]
0.0023
[4]
0.118
[5]
Reactome
[48] array · 6 items
[0]
Platelet activation - Homo sapiens (human)
[1]
131
[2]
29 (22.1%)
[3]
0.00239
[4]
0.118
[5]
KEGG
[49] array · 6 items
[0]
Adipogenesis
[1]
131
[2]
29 (22.1%)
[3]
0.00239
[4]
0.118
[5]
Wikipathways
[50] array · 6 items
[0]
Downstream signal transduction
[1]
279
[2]
53 (19.0%)
[3]
0.00242
[4]
0.118
[5]
Reactome
[51] array · 6 items
[0]
Signaling by EGFR
[1]
292
[2]
55 (18.8%)
[3]
0.00246
[4]
0.118
[5]
Reactome
[52] array · 6 items
[0]
Regulation of nuclear beta catenin signaling and target gene transcription
[1]
80
[2]
20 (25.0%)
[3]
0.00248
[4]
0.118
[5]
PID
[53] array · 6 items
[0]
Validated nuclear estrogen receptor alpha network
[1]
64
[2]
17 (26.6%)
[3]
0.00257
[4]
0.118
[5]
PID
[54] array · 6 items
[0]
NCAM signaling for neurite out-growth
[1]
223
[2]
44 (19.7%)
[3]
0.0026
[4]
0.118
[5]
Reactome
[55] array · 6 items
[0]
Downstream signaling events of B Cell Receptor (BCR)
[1]
120
[2]
27 (22.5%)
[3]
0.0026
[4]
0.118
[5]
Reactome
[56] array · 6 items
[0]
BMP signaling Dro
[1]
34
[2]
11 (32.4%)
[3]
0.00275
[4]
0.122
[5]
INOH
[57] array · 6 items
[0]
Signaling by Leptin
[1]
193
[2]
39 (20.2%)
[3]
0.00287
[4]
0.124
[5]
Reactome
[58] array · 6 items
[0]
Inactivation of Cdc42 and Rac
[1]
9
[2]
5 (55.6%)
[3]
0.00291
[4]
0.124
[5]
Reactome
[59] array · 6 items
[0]
DAP12 signaling
[1]
282
[2]
53 (18.8%)
[3]
0.00306
[4]
0.129
[5]
Reactome
[60] array · 6 items
[0]
Mesodermal Commitment Pathway
[1]
76
[2]
19 (25.0%)
[3]
0.00314
[4]
0.129
[5]
Wikipathways
[61] array · 6 items
[0]
Insulin receptor signalling cascade
[1]
238
[2]
46 (19.3%)
[3]
0.00321
[4]
0.129
[5]
Reactome
[62] array · 6 items
[0]
regulation of pgc-1a
[1]
21
[2]
8 (38.1%)
[3]
0.00332
[4]
0.129
[5]
BioCarta
[63] array · 6 items
[0]
EPH-ephrin mediated repulsion of cells
[1]
30
[2]
10 (33.3%)
[3]
0.00332
[4]
0.129
[5]
Reactome
[64] array · 6 items
[0]
Retinoic acid receptors-mediated signaling
[1]
30
[2]
10 (33.3%)
[3]
0.00332
[4]
0.129
[5]
PID
[65] array · 6 items
[0]
FoxO signaling pathway - Homo sapiens (human)
[1]
134
[2]
29 (21.6%)
[3]
0.0034
[4]
0.13
[5]
KEGG
[66] array · 6 items
[0]
Interleukin receptor SHC signaling
[1]
195
[2]
39 (20.0%)
[3]
0.00346
[4]
0.13
[5]
Reactome
[67] array · 6 items
[0]
NGF signalling via TRKA from the plasma membrane
[1]
310
[2]
57 (18.4%)
[3]
0.00361
[4]
0.133
[5]
Reactome
[68] array · 6 items
[0]
NRAGE signals death through JNK
[1]
45
[2]
13 (28.9%)
[3]
0.00363
[4]
0.133
[5]
Reactome
[69] array · 6 items
[0]
Constitutive Signaling by Aberrant PI3K in Cancer
[1]
61
[2]
16 (26.2%)
[3]
0.00389
[4]
0.14
[5]
Reactome
[70] array · 6 items
[0]
AMPK signaling pathway - Homo sapiens (human)
[1]
124
[2]
27 (21.8%)
[3]
0.00422
[4]
0.148
[5]
KEGG
[71] array · 6 items
[0]
MAPK1/MAPK3 signaling
[1]
191
[2]
38 (19.9%)
[3]
0.00424
[4]
0.148
[5]
Reactome
[72] array · 6 items
[0]
Signaling by VEGF
[1]
274
[2]
51 (18.6%)
[3]
0.00444
[4]
0.149
[5]
Reactome
[73] array · 6 items
[0]
Wnt Signaling Pathway and Pluripotency
[1]
101
[2]
23 (22.8%)
[3]
0.00445
[4]
0.149
[5]
Wikipathways
[74] array · 6 items
[0]
VEGFR2 mediated cell proliferation
[1]
198
[2]
39 (19.7%)
[3]
0.00455
[4]
0.149
[5]
Reactome
[75] array · 6 items
[0]
FRS-mediated FGFR2 signaling
[1]
186
[2]
37 (19.9%)
[3]
0.00475
[4]
0.149
[5]
Reactome
[76] array · 6 items
[0]
FRS-mediated FGFR1 signaling
[1]
186
[2]
37 (19.9%)
[3]
0.00475
[4]
0.149
[5]
Reactome
[77] array · 6 items
[0]
FRS-mediated FGFR3 signaling
[1]
186
[2]
37 (19.9%)
[3]
0.00475
[4]
0.149
[5]
Reactome
[78] array · 6 items
[0]
FRS-mediated FGFR4 signaling
[1]
186
[2]
37 (19.9%)
[3]
0.00475
[4]
0.149
[5]
Reactome
[79] array · 6 items
[0]
Dilated cardiomyopathy - Homo sapiens (human)
[1]
90
[2]
21 (23.3%)
[3]
0.00475
[4]
0.149
[5]
KEGG
[80] array · 6 items
[0]
repression of WNT target genes
[1]
10
[2]
5 (50.0%)
[3]
0.00519
[4]
0.16
[5]
Reactome
[81] array · 6 items
[0]
MAPK family signaling cascades
[1]
225
[2]
43 (19.1%)
[3]
0.00529
[4]
0.16
[5]
Reactome
[82] array · 6 items
[0]
MAPK signaling pathway - Homo sapiens (human)
[1]
257
[2]
48 (18.7%)
[3]
0.00529
[4]
0.16
[5]
KEGG
[83] array · 6 items
[0]
transcription regulation by methyltransferase of carm1
[1]
14
[2]
6 (42.9%)
[3]
0.00556
[4]
0.16
[5]
BioCarta
[84] array · 6 items
[0]
Netrin-1 signaling
[1]
37
[2]
11 (29.7%)
[3]
0.0057
[4]
0.16
[5]
Reactome
[85] array · 6 items
[0]
IRS-related events triggered by IGF1R
[1]
239
[2]
45 (18.8%)
[3]
0.00583
[4]
0.16
[5]
Reactome
[86] array · 6 items
[0]
IGF1R signaling cascade
[1]
239
[2]
45 (18.8%)
[3]
0.00583
[4]
0.16
[5]
Reactome
[87] array · 6 items
[0]
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
[1]
239
[2]
45 (18.8%)
[3]
0.00583
[4]
0.16
[5]
Reactome
[88] array · 6 items
[0]
Neuronal System
[1]
291
[2]
53 (18.2%)
[3]
0.00595
[4]
0.16
[5]
Reactome
[89] array · 6 items
[0]
DAP12 interactions
[1]
298
[2]
54 (18.1%)
[3]
0.00614
[4]
0.16
[5]
Reactome
[90] array · 6 items
[0]
Gastric acid secretion - Homo sapiens (human)
[1]
75
[2]
18 (24.0%)
[3]
0.00631
[4]
0.16
[5]
KEGG
[91] array · 6 items
[0]
Fatty acid, triacylglycerol, and ketone body metabolism
[1]
98
[2]
22 (22.4%)
[3]
0.00637
[4]
0.16
[5]
Reactome
[92] array · 6 items
[0]
PIP3 activates AKT signaling
[1]
98
[2]
22 (22.4%)
[3]
0.00637
[4]
0.16
[5]
Reactome
[93] array · 6 items
[0]
PI-3K cascade:FGFR2
[1]
98
[2]
22 (22.4%)
[3]
0.00637
[4]
0.16
[5]
Reactome
[94] array · 6 items
[0]
PI-3K cascade:FGFR1
[1]
98
[2]
22 (22.4%)
[3]
0.00637
[4]
0.16
[5]
Reactome
[95] array · 6 items
[0]
PI-3K cascade:FGFR3
[1]
98
[2]
22 (22.4%)
[3]
0.00637
[4]
0.16
[5]
Reactome
[96] array · 6 items
[0]
PI-3K cascade:FGFR4
[1]
98
[2]
22 (22.4%)
[3]
0.00637
[4]
0.16
[5]
Reactome
[97] array · 6 items
[0]
PI3K events in ERBB4 signaling
[1]
98
[2]
22 (22.4%)
[3]
0.00637
[4]
0.16
[5]
Reactome
[98] array · 6 items
[0]
PI3K events in ERBB2 signaling
[1]
98
[2]
22 (22.4%)
[3]
0.00637
[4]
0.16
[5]
Reactome
[99] array · 6 items
[0]
VEGFA-VEGFR2 Pathway
[1]
266
[2]
49 (18.4%)
[3]
0.00639
[4]
0.16
[5]
Reactome
[100] array · 6 items
[0]
Collagen biosynthesis and modifying enzymes
[1]
64
[2]
16 (25.0%)
[3]
0.00644
[4]
0.16
[5]
Reactome
[101] array · 6 items
[0]
IRS-mediated signalling
[1]
235
[2]
44 (18.7%)
[3]
0.00704
[4]
0.173
[5]
Reactome
[102] array · 6 items
[0]
O-linked glycosylation
[1]
105
[2]
23 (21.9%)
[3]
0.00731
[4]
0.173
[5]
Reactome
[103] array · 6 items
[0]
RAF/MAP kinase cascade
[1]
185
[2]
36 (19.5%)
[3]
0.00759
[4]
0.173
[5]
Reactome
[104] array · 6 items
[0]
SHC1 events in EGFR signaling
[1]
185
[2]
36 (19.5%)
[3]
0.00759
[4]
0.173
[5]
Reactome
[105] array · 6 items
[0]
SOS-mediated signalling
[1]
185
[2]
36 (19.5%)
[3]
0.00759
[4]
0.173
[5]
Reactome
[106] array · 6 items
[0]
GRB2 events in EGFR signaling
[1]
185
[2]
36 (19.5%)
[3]
0.00759
[4]
0.173
[5]
Reactome
[107] array · 6 items
[0]
SHC1 events in ERBB2 signaling
[1]
185
[2]
36 (19.5%)
[3]
0.00759
[4]
0.173
[5]
Reactome
[108] array · 6 items
[0]
SHC1 events in ERBB4 signaling
[1]
185
[2]
36 (19.5%)
[3]
0.00759
[4]
0.173
[5]
Reactome
[109] array · 6 items
[0]
GRB2 events in ERBB2 signaling
[1]
185
[2]
36 (19.5%)
[3]
0.00759
[4]
0.173
[5]
Reactome
[110] array · 6 items
[0]
Regulation of Commissural axon pathfinding by Slit and Robo
[1]
4
[2]
3 (75.0%)
[3]
0.00784
[4]
0.175
[5]
Reactome
[111] array · 6 items
[0]
Fosphenytoin (Antiarrhythmic) Metabolism Pathway
[1]
4
[2]
3 (75.0%)
[3]
0.00784
[4]
0.175
[5]
SMPDB
[112] array · 6 items
[0]
Ephrin B reverse signaling
[1]
24
[2]
8 (33.3%)
[3]
0.0084
[4]
0.186
[5]
PID
[113] array · 6 items
[0]
Signaling by Interleukins
[1]
270
[2]
49 (18.1%)
[3]
0.00851
[4]
0.186
[5]
Reactome
[114] array · 6 items
[0]
Transport of organic anions
[1]
11
[2]
5 (45.5%)
[3]
0.00852
[4]
0.186
[5]
Reactome
[115] array · 6 items
[0]
Rho GTPase cycle
[1]
125
[2]
26 (20.8%)
[3]
0.00914
[4]
0.194
[5]
Reactome
[116] array · 6 items
[0]
PI3K/AKT activation
[1]
101
[2]
22 (21.8%)
[3]
0.00918
[4]
0.194
[5]
Reactome
[117] array · 6 items
[0]
Thyroid hormone signaling pathway - Homo sapiens (human)
[1]
119
[2]
25 (21.0%)
[3]
0.0092
[4]
0.194
[5]
KEGG
[118] array · 6 items
[0]
Signaling by NOTCH
[1]
107
[2]
23 (21.5%)
[3]
0.00923
[4]
0.194
[5]
Reactome
[119] array · 6 items
[0]
Cell death signalling via NRAGE, NRIF and NADE
[1]
61
[2]
15 (24.6%)
[3]
0.0096
[4]
0.2
[5]
Reactome
row_count
120
locator
section[3]/table-wrap[2]#t0010
[6] object · 16 fields
id
asset:table:pmid:29201983:5
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:e78853399a1c568de357199c8a538754a6fb4926905f7241b56431765a03fa06
bytes
3733
access
open
state
verified
reader
read_table
reader_status
available
identifier
section[3]/table-wrap[3]#t0015
version
null
note
Names and FCs of the 33 neighbors of the EntrezGene ID 2033 (see Fig. 1) after the exposure of PHHs for 5 days daily to VPA. PHHs, primary human hepatocytes; VPA, valproic acid; FCs, fold changes.
structure object · 5 fields
pmcid
PMC5702865
section_index
3
section_title
Data
row_count
53
column_count
5
table object · 8 fields
label
Table 3
caption
Names and FCs of the 33 neighbors of the EntrezGene ID 2033 (see Fig. 1) after the exposure of PHHs for 5 days daily to VPA. PHHs, primary human hepatocytes; VPA, valproic acid; FCs, fold changes.
rows array · 53 items
[0] array · 5 items
[0]
Entrez Gene ID
[1]
Gene Symbol
[2]
Gene Name
[3]
MeDIP-seq FCs
[4]
Steatosis-related pathway(s)
[1] array · 5 items
[0]
354
[1]
KLK3
[2]
kallikrein-related peptidase 3
[3]
1.9
[4]
–
[2] array · 5 items
[0]
595
[1]
CCND1
[2]
cyclin D1
[3]
2.1
[4]
–
[3] array · 5 items
[0]
864
[1]
RUNX3
[2]
runt-related transcription factor 3
[3]
2
[4]
–
[4] array · 5 items
[0]
[1]
[2]
[3]
[4]
[5] array · 5 items
[0]
1026
[1]
CDKN1A
[2]
cyclin-dependent kinase inhibitor 1 A (p21, Cip1)
[3]
-3.5
[4]
Adipogenesis
[6] array · 1 item
[0]
Signaling events mediated by HDAC Class III
[7] array · 5 items
[0]
[1]
[2]
[3]
[4]
[8] array · 5 items
[0]
1387
[1]
CREBBP
[2]
CREB binding protein
[3]
-3.2
[4]
Signaling events mediated by HDAC Class III
[9] array · 1 item
[0]
Transcriptional regulation of white adipocyte differentiation
[10] array · 1 item
[0]
Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
[11] array · 1 item
[0]
Signaling events mediated by HDAC Class I
[12] array · 1 item
[0]
Fatty acid, triacylglycerol, and ketone body metabolism
[13] array · 5 items
[0]
1488
[1]
CTBP2
[2]
C-terminal binding protein 2
[3]
-3.9
[4]
–
[14] array · 5 items
[0]
1844
[1]
DUSP2
[2]
dual specificity phosphatase 2
[3]
2.4
[4]
–
[15] array · 5 items
[0]
1958
[1]
EGR1
[2]
early growth response 1
[3]
-3.6
[4]
–
[16] array · 5 items
[0]
[1]
[2]
[3]
[4]
[17] array · 5 items
[0]
2033
[1]
EP300
[2]
E1A binding protein p300
[3]
-5.2
[4]
Signaling events mediated by HDAC Class III
[18] array · 1 item
[0]
Transcriptional regulation of white adipocyte differentiation
[19] array · 1 item
[0]
Signaling events mediated by HDAC Class I
[20] array · 5 items
[0]
2309
[1]
FOXO3
[2]
forkhead box O3
[3]
2.2
[4]
Signaling events mediated by HDAC Class III
[21] array · 5 items
[0]
2353
[1]
FOS
[2]
FBJ murine osteosarcoma viral oncogene homolog
[3]
-3.5
[4]
–
[22] array · 5 items
[0]
2626
[1]
GATA4
[2]
GATA binding protein 4
[3]
2.5
[4]
Adipogenesis
[23] array · 5 items
[0]
4088
[1]
SMAD3
[2]
SMAD family member 3
[3]
2.4
[4]
Adipogenesis
[24] array · 5 items
[0]
4205
[1]
MEF2A
[2]
myocyte enhancer factor 2 A
[3]
2.2
[4]
Adipogenesis
[25] array · 5 items
[0]
4772
[1]
NFATC1
[2]
nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1
[3]
1.8
[4]
–
[26] array · 5 items
[0]
5594
[1]
MAPK1
[2]
mitogen-activated protein kinase 1
[3]
2.3
[4]
–
[27] array · 5 items
[0]
5914
[1]
RARA
[2]
retinoic acid receptor, alpha
[3]
-3.8
[4]
Adipogenesis
[28] array · 5 items
[0]
6095
[1]
RORA
[2]
RAR-related orphan receptor A
[3]
-4
[4]
Adipogenesis
[29] array · 5 items
[0]
[1]
[2]
[3]
[4]
[30] array · 5 items
[0]
6256
[1]
RXRA
[2]
retinoid X receptor, alpha
[3]
-3.8
[4]
Adipogenesis
[31] array · 1 item
[0]
Transcriptional regulation of white adipocyte differentiation
[32] array · 1 item
[0]
Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
[33] array · 1 item
[0]
Fatty acid, triacylglycerol, and ketone body metabolism
[34] array · 5 items
[0]
6670
[1]
SP3
[2]
Sp3 transcription factor
[3]
-4.1
[4]
–
[35] array · 5 items
[0]
6776
[1]
STAT5A
[2]
signal transducer and activator of transcription 5 A
[3]
2.2
[4]
Adipogenesis
[36] array · 5 items
[0]
6925
[1]
TCF4
[2]
transcription factor 4
[3]
-4
[4]
–
[37] array · 5 items
[0]
6929
[1]
TCF3
[2]
transcription factor 3
[3]
2.1
[4]
–
[38] array · 5 items
[0]
6934
[1]
TCF7L2
[2]
transcription factor 7-like 2 (T-cell specific, HMG-box)
[3]
-3.4
[4]
–
[39] array · 5 items
[0]
6938
[1]
TCF12
[2]
transcription factor 12
[3]
2.12
[4]
–
[40] array · 5 items
[0]
7026
[1]
NR2F2
[2]
nuclear receptor subfamily 2, group F, member 2
[3]
2.6
[4]
–
[41] array · 5 items
[0]
7161
[1]
TP73
[2]
tumor protein p73
[3]
2.5
[4]
–
[42] array · 5 items
[0]
9252
[1]
RPS6KA5
[2]
ribosomal protein S6 kinase, 90 kDa, polypeptide 5
[3]
-3.9
[4]
–
[43] array · 5 items
[0]
9314
[1]
9314
[2]
Kruppel-like factor 4 (gut)
[3]
2.7
[4]
–
[44] array · 5 items
[0]
[1]
[2]
[3]
[4]
[45] array · 5 items
[0]
9611
[1]
NCOR1
[2]
nuclear receptor corepressor 1
[3]
-3.4
[4]
Adipogenesis
[46] array · 1 item
[0]
Transcriptional regulation of white adipocyte differentiation
[47] array · 1 item
[0]
Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)
[48] array · 1 item
[0]
Signaling events mediated by HDAC Class I
[49] array · 1 item
[0]
Fatty acid, triacylglycerol, and ketone body metabolism
[50] array · 5 items
[0]
10365
[1]
KLF2
[2]
Kruppel-like factor 2
[3]
-3.3
[4]
Signaling events mediated by HDAC Class III
[51] array · 5 items
[0]
23411
[1]
SIRT1
[2]
sirtuin 1
[3]
-3.5
[4]
[52] array · 5 items
[0]
90427
[1]
BMF
[2]
Bcl2 modifying facto
[3]
2.2
[4]
locator
section[3]/table-wrap[3]#t0015
gaps array · 2 items
[0]
asset:data:geo:E-MTAB-4437 not downloaded
[1]
asset:data:geo:E-MTAB-4437 licence not read
analysis object · 4 fields
state
complete
methods array · 1 item
[0] object · 10 fields
id
method-1
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
1
band
verbatim
quote
Statistical analysis was performed applying the default parameters of MEDIPS, using the edgeR module, an empirical analysis of digital gene expression data in R that uses Bayes estimation and exact tests based on the negative binomial distribution [8].
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: edger.
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 · 1 item
[0]
E-MTAB-4437
resolved_accessions array · 1 item
[0]
E-MTAB-4437
statements array · 1 item
[0]
MeDIP-seq raw data are available on ArrayExpress (accession number: E-MTAB-4437).
basis
The paper names E-MTAB-4437 in ArrayExpress 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:29201983
[1]
data:geo:E-MTAB-4437
[2]
asset:table:pmid:29201983:1
[3]
asset:table:pmid:29201983:2
[4]
asset:table:pmid:29201983:3
[5]
asset:table:pmid:29201983:4
[6]
asset:table:pmid:29201983:5
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:E-MTAB-4437
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
2026-10-31T18:32:59Z
independence
same_provider
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
8
usage object · 3 fields
prompt_tokens
70803
completion_tokens
2692
cached_tokens
1832
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:29201983
type
paper
label
pmid:29201983
[1] object · 3 fields
id
source:pmid:29201983
type
manuscript
label
PMID 29201983 full text
[2] object · 3 fields
id
data:geo:E-MTAB-4437
type
dataset
label
GEO E-MTAB-4437
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:29201983
type
paper
label
pmid:29201983
[1] object · 3 fields
id
source:pmid:29201983
type
manuscript
label
PMID 29201983 full text
[2] object · 3 fields
id
data:geo:E-MTAB-4437
type
dataset
label
GEO E-MTAB-4437
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-29201983
type
extraction
used array · 1 item
[0]
source:pmid:29201983
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-E-MTAB-4437
type
accession_resolution
used array · 1 item
[0]
data:geo:E-MTAB-4437
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:29201983
parent_hash
sha256:6221264eefdb6a472fbebce8fab02587c0ec1a37704c1a33ea658282b3d422be
fork_of
null
gaps array · 6 items
[0]
asset:data:geo:E-MTAB-4437 licence not read
[1]
asset:data:geo:E-MTAB-4437 not downloaded
[2]
execution.not_run
[3]
review.human_critique
[4]
review.independent_reader
[5]
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]
riability in susceptibility to toxicants and cultured in 6-well plates in a collagen sandwich [2], ac
order_basis
paper_text_order:1590
id
assay:1
[1] object · 11 fields
role
analysis
definition_id
differential_expression
definition_version
f2132e96ae6c7a4e
required_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
Statistical analysis was performed applying the default parameters of MEDIPS, using the edgeR module, an empirical analysis of digital gene expression data in R that uses Bayes estimation and exact tests based on the negative binomial distribution [8].
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:29201983", "kind": "science-record", "revision": 8, "content_hash": "sha256:0548d61cb491c96723c34cd807d8ac4ba9da3ee4c9a3c97f23918a284c109f57", "created_at": "2026-11-01T15:40:30Z", "updated_at": "2026-11-01T22:43:10Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Data on novel DNA methylation changes induced by valproic acid in human hepatocytes.", "doi": "10.1016/j.dib.2017.11.031", "pmid": "29201983", "authors": ["JarnoEJ Wolters", "SimoneGJ van Breda", "SandraM Claessen", "TheoMCM de Kok", "JosCS Kleinjans"], "journal": "Data in brief", "year": 2018, "abstract": "Valproic acid (VPA) is a widely prescribed antiepileptic drug in the world. Despite its pharmacological importance, it may cause liver toxicity and steatosis. However the exact mechanism of the steatosis formation is unknown. The data presented in this DIB publication is used to further investigate the VPA-induced mechanisms of steatosis by analyzing changes in patterns of methylation. Therefore, primary human hepatocytes (PHHs) were exposed to VPA at a concentration which was shown to cause steatosis without inducing overt cytotoxicity. VPA was administered for 5 days daily to PHHs. Furthermore, after 5 days VPA-treatment parts of the PHHs were followed for a 3 days washout. Differentially methylated DNA regions (DMRs) were identified by using the 'Methylated DNA Immuno-Precipitation - sequencing' (MeDIP-seq) method. The data presented in this DIB demonstrate induced steatosis pathways by all DMRs during VPA-treatment, covering interesting drug-induced steatosis genes (persistent DMRs upon terminating VPA treatment and the EP300 network). This was illustrated in our associated article (Wolters et al., 2017) [1]. MeDIP-seq raw data are available on ArrayExpress (accession number: E-MTAB-4437).", "claims": [{"id": "claim-method", "statement": "Statistical analysis was performed applying the default parameters of MEDIPS, using the edgeR module, an empirical analysis of digital gene expression data in R that uses Bayes estimation and exact tests based on the negative binomial distribution [8].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29201983", "locator": "sections[15] \"MeDIP-Seq analysis\" paragraph 2", "quote": "Statistical analysis was performed applying the default parameters of MEDIPS, using the edgeR module, an empirical analysis of digital gene expression data in R that uses Bayes estimation and exact tests based on the negative binomial distribution [8]."}], "state": "complete"}, {"id": "claim-data-access", "statement": "MeDIP-seq raw data are available on ArrayExpress (accession number: E-MTAB-4437).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:29201983", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "MeDIP-seq raw data are available on ArrayExpress (accession number: E-MTAB-4437)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified DMRs using MEDIPS with edgeR, negative-binomial exact tests, and TMM normalization, and the raw MeDIP-seq source data are available through ArrayExpress under accession E-MTAB-4437.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:29201983", "locator": "sections[15] \"MeDIP-Seq analysis\" paragraph 2", "quote": "The MEDIPS package (version 1.16.0, Bioconductor) was used for the analysis of the MeDIP-seq data [4], [5], [6]."}, {"asset": "source:pmid:29201983", "locator": "sections[15] \"MeDIP-Seq analysis\" paragraph 2", "quote": "Statistical analysis was performed applying the default parameters of MEDIPS, using the edgeR module, an empirical analysis of digital gene expression data in R that uses Bayes estimation and exact tests based on the negative binomial distribution [8]."}, {"asset": "source:pmid:29201983", "locator": "sections[15] \"MeDIP-Seq analysis\" paragraph 2", "quote": "Notably, raw count data was normalized using the weighted trimmed mean of M-values (TMM-normalization)."}, {"asset": "source:pmid:29201983", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "MeDIP-seq raw data are available on ArrayExpress (accession number: E-MTAB-4437)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified DMRs using MEDIPS with edgeR, negative-binomial exact tests, and TMM normalization, and the raw MeDIP-seq source data are available through ArrayExpress under accession E-MTAB-4437.", "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:29201983"], "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:E-MTAB-4437"], "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:E-MTAB-4437"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:29201983", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1016/j.dib.2017.11.031", "sha256": "sha256:f151e07c703e859065645d9b79cc20cbf853ff88108d96748f7b1dbd284444a4", "bytes": 28965, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1016/j.dib.2017.11.031", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC5702865", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:E-MTAB-4437", "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=E-MTAB-4437", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "E-MTAB-4437", "version": null, "note": "MeDIP-seq raw data are available on ArrayExpress (accession number: E-MTAB-4437).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "MeDIP-seq raw data are available on ArrayExpress (accession number: E-MTAB-4437).", "access_statement_kind": "data_availability_statement", "sample_accessions": [], "sample_count": null, "group_sizes": null, "group_sizes_basis": null, "platform": null, "taxon": null, "title": null, "resolution_checked_at": "2026-10-31T18:29:00Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:29201983:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:18f54bc4a960e8e7ca6a820403c3d9baa0f794d1795c31d2365fcfee51c5741e", "bytes": 1158, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[1]/table-wrap[1]#t0020", "version": null, "note": null, "structure": {"pmcid": "PMC5702865", "section_index": 1, "section_title": "p", "row_count": 10, "column_count": 2}, "table": {"label": null, "caption": null, "rows": [["Subject area", "Biology"], ["More specific subject area", "(Hepato)toxicogenomics"], ["Type of data", "Figure and Tables"], ["How data was acquired", "Illumina HiSeq. 2000 sequencer"], ["Data format", "Differentially methylated DNA regions/genes, pathways, statistical analysis"], ["Experimental factors", "Primary human hepatocytes (PHHs) were treated by valproic acid (VPA) at an incubation concentration of 15 mM for 5 days daily followed by a washout of 3 days"], ["Experimental features", "The treated samples were corrected for time-matched vehicle controls."], ["The persistent changes were identified by determining DNA methylation similarities between samples of 5 days daily VPA-treatment and samples of 3 days washout upon the 5 days daily VPA-treatment"], ["Data source location", "Department of Toxicogenomics, Maastricht University, the Netherlands"], ["Data accessibility", "Methylated DNA Immuno-Precipitation – sequencing (MeDIP-seq) raw data are available on ArrayExpress (accession number: E-MTAB-4437)."]], "row_count": 10, "column_count": 2, "numeric_cells": 4, "header_rows": 1, "locator": "section[1]/table-wrap[1]#t0020"}}, {"id": "asset:table:pmid:29201983:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:18f54bc4a960e8e7ca6a820403c3d9baa0f794d1795c31d2365fcfee51c5741e", "bytes": 1158, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[1]/table-wrap[1]#t0020", "version": null, "note": null, "structure": {"pmcid": "PMC5702865", "section_index": 2, "section_title": "p", "row_count": 10, "column_count": 2}, "table": {"label": null, "caption": null, "rows": [["Subject area", "Biology"], ["More specific subject area", "(Hepato)toxicogenomics"], ["Type of data", "Figure and Tables"], ["How data was acquired", "Illumina HiSeq. 2000 sequencer"], ["Data format", "Differentially methylated DNA regions/genes, pathways, statistical analysis"], ["Experimental factors", "Primary human hepatocytes (PHHs) were treated by valproic acid (VPA) at an incubation concentration of 15 mM for 5 days daily followed by a washout of 3 days"], ["Experimental features", "The treated samples were corrected for time-matched vehicle controls."], ["The persistent changes were identified by determining DNA methylation similarities between samples of 5 days daily VPA-treatment and samples of 3 days washout upon the 5 days daily VPA-treatment"], ["Data source location", "Department of Toxicogenomics, Maastricht University, the Netherlands"], ["Data accessibility", "Methylated DNA Immuno-Precipitation – sequencing (MeDIP-seq) raw data are available on ArrayExpress (accession number: E-MTAB-4437)."]], "row_count": 10, "column_count": 2, "numeric_cells": 4, "header_rows": 1, "locator": "section[1]/table-wrap[1]#t0020"}}, {"id": "asset:table:pmid:29201983:3", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:8362607f585827fe84b98783a7b872ec4ae2ef16328be52828ffeaddcaee9581", "bytes": 3362, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[1]#t0005", "version": null, "note": "Names and functions of the 20 persistently hypermethylated DMRs annotated to 15 unique Entrez Genes (A) and the 11 hypomethylated DMRs annotated to 9 unique Entrez Genes (B) of the MEDIP-seq analysis after the exposure of PHHs for 5 days daily to VPA followed by 3 days washout. PHHs, primary human hepatocytes; VPA, valproic acid; DMRs, differentially methylated DNA regions.", "structure": {"pmcid": "PMC5702865", "section_index": 3, "section_title": "Data", "row_count": 31, "column_count": 4}, "table": {"label": "Table 1", "caption": "Names and functions of the 20 persistently hypermethylated DMRs annotated to 15 unique Entrez Genes (A) and the 11 hypomethylated DMRs annotated to 9 unique Entrez Genes (B) of the MEDIP-seq analysis after the exposure of PHHs for 5 days daily to VPA followed by 3 days washout. PHHs, primary human hepatocytes; VPA, valproic acid; DMRs, differentially methylated DNA regions.", "rows": [["A) 20 persistently hypermethylated DMRs annotated to 15 unique Entrez Genes"], ["Entrez Gene ID", "Gene Symbol", "Gene Name", "NCBI Gene Function"], ["114", "ADCY8", "adenylate cyclase 8 (brain)", "membrane bound enzyme that catalyses the formation of cyclic AMP from ATP"], ["5099", "PCDH7", "protocadherin 7", "The gene product is an integral membrane protein that is thought to function in cell-cell recognition and adhesion"], ["7625", "ZNF74", "zinc finger protein 74", "–"], ["23078", "VWA8", "von Willebrand factor A domain containing 8", "–"], ["55591", "VEZT", "vezatin, adherens junctions transmembrane protein", "This gene encodes a transmembrane protein which has been localized to adherens junctions and shown to bind to myosin VIIA"], ["57521", "RPTOR", "regulatory associated protein of MTOR, complex 1", "encodes a component of a signaling pathway that regulates cell growth in response to nutrient and insulin levels"], ["79755", "ZNF750", "zinc finger protein 750", "This gene encodes a protein with a nuclear localization site and a C2H2 zinc finger domain. Mutations in this gene have been associated with seborrhea-like dermatitis with psoriasiform elements."], ["80757", "TMEM121", "transmembrane protein 121", "–"], ["114784", "CSMD2", "CUB and Sushi multiple domains 2", "–"], ["122706", "PSMB11", "proteasome (prosome, macropain) subunit, beta type, 11", "Proteasomes generate peptides that are presented by major histocompatibility complex (MHC) I molecules to other cells of the immune system."], ["254827", "NAALADL2", "N-acetylated alpha-linked acidic dipeptidase-like 2", "–"], ["338707", "B4GALNT4", "beta-1,4-N-acetyl-galactosaminyl transferase 4", "–"], ["388228", "SBK1", "SH3 domain binding kinase 1", "–"], ["440073", "IQSEC. 3", "IQ motif and Sec. 7 domain 3", "–"], ["100507290", "ZNF865", "zinc finger protein 865", "–"], [""], ["B) 11 persistently hypomethylated DMRs annotated to 9 unique Entrez Genes"], [""], ["Entrez Gene ID", "Gene Symbol", "Gene Name", "NCBI Gene Function"], [""], ["290", "ANPEP", "alanyl (membrane) aminopeptidase", "Aminopeptidase N is located in the small-intestinal and renal microvillar membrane, and also in other plasma membranes. In the small intestine aminopeptidase N plays a role in the final digestion of peptides generated from hydrolysis of proteins by gastric and pancreatic proteases."], ["29982", "NRBF2", "nuclear receptor binding factor 2", "–"], ["136051", "ZNF786", "zinc finger protein 786", "–"], ["414763", "BMS1P18", "BMS1 ribosome biogenesis factor pseudogene 18", "–"], ["643955", "ZNF733P", "zinc finger protein 733, pseudogene", "–"], ["646096", "CHEK2P2", "checkpoint kinase 2 pseudogene 2", "–"], ["647121", "EMBP1", "embigin pseudogene 1", "–"], ["100101266", "HAVCR1P1", "hepatitis A virus cellular receptor 1 pseudogene 1", "–"], ["101927554", "LINC01250", "long intergenic non-protein coding RNA 1250", "–"]], "row_count": 31, "column_count": 4, "numeric_cells": 58, "header_rows": 2, "locator": "section[3]/table-wrap[1]#t0005"}}, {"id": "asset:table:pmid:29201983:4", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:c6f21f6213cb8cc77cd1a615eb078d7ef244d8e9a81be872f33d60ef4d672509", "bytes": 10824, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[2]#t0010", "version": null, "note": "The ‘enriched pathway-based sets’ from the HOMER annotated genes of the 3006 hypermethylated DMRs and the 3077 hypomethylated DMRs after the exposure of PHHs for 5 days daily to VPA. PHHs, primary human hepatocytes; VPA, valproic acid; DMRs, differentially methylated DNA regions.", "structure": {"pmcid": "PMC5702865", "section_index": 3, "section_title": "Data", "row_count": 120, "column_count": 6}, "table": {"label": "Table 2", "caption": "The ‘enriched pathway-based sets’ from the HOMER annotated genes of the 3006 hypermethylated DMRs and the 3077 hypomethylated DMRs after the exposure of PHHs for 5 days daily to VPA. PHHs, primary human hepatocytes; VPA, valproic acid; DMRs, differentially methylated DNA regions.", "rows": [["Pathway name", "Set size", "Candidates, contained", "p-value", "q-value", "Pathway source"], ["Developmental Biology", "586", "129 (22.0%)", "3.23E-10", "8.02E-07", "Reactome"], ["Axon guidance", "459", "101 (22.0%)", "3.06E-08", "3.81E-05", "Reactome"], ["Wnt signaling pathway - Homo sapiens (human)", "140", "36 (25.7%)", "3.17E-05", "0.0262", "KEGG"], ["Axon guidance - Homo sapiens (human)", "127", "33 (26.0%)", "5.33E-05", "0.0331", "KEGG"], ["Signalling by NGF", "386", "76 (19.7%)", "9.86E-05", "0.0447", "Reactome"], ["Signaling by SCF-KIT", "264", "56 (21.2%)", "0.000108", "0.0447", "Reactome"], ["Hippo signaling pathway - Homo sapiens (human)", "154", "36 (23.4%)", "0.000257", "0.0914", "KEGG"], ["Diseases of signal transduction", "180", "40 (22.2%)", "0.000373", "0.097", "Reactome"], ["Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)", "20", "9 (45.0%)", "0.00044", "0.097", "Reactome"], ["Oxytocin signaling pathway - Homo sapiens (human)", "159", "36 (22.6%)", "0.000494", "0.097", "KEGG"], ["BMP2 signaling TGF-beta MV", "56", "17 (30.4%)", "0.000501", "0.097", "INOH"], ["Fc gamma R-mediated phagocytosis - Homo sapiens (human)", "92", "24 (26.1%)", "0.000502", "0.097", "KEGG"], ["effects of calcineurin in keratinocyte differentiation", "13", "7 (53.8%)", "0.000508", "0.097", "BioCarta"], ["NOTCH1 Intracellular Domain Regulates Transcription", "47", "15 (31.9%)", "0.000587", "0.104", "Reactome"], ["Calcium signaling pathway - Homo sapiens (human)", "180", "39 (21.7%)", "0.000741", "0.118", "KEGG"], ["Signaling by ERBB4", "263", "52 (19.8%)", "0.00107", "0.118", "Reactome"], ["Signaling by PDGF", "301", "58 (19.3%)", "0.0011", "0.118", "Reactome"], ["Signaling by FGFR3", "270", "53 (19.6%)", "0.00114", "0.118", "Reactome"], ["Signaling by FGFR4", "270", "53 (19.6%)", "0.00114", "0.118", "Reactome"], ["Signaling by FGFR1", "271", "53 (19.6%)", "0.00125", "0.118", "Reactome"], ["Extrinsic Pathway of Fibrin Clot Formation", "5", "4 (80.0%)", "0.00126", "0.118", "Reactome"], ["G alpha (12/13) signalling events", "76", "20 (26.3%)", "0.00127", "0.118", "Reactome"], ["alk in cardiac myocytes", "27", "10 (37.0%)", "0.00134", "0.118", "BioCarta"], ["TGF-beta super family signaling pathway canonical", "115", "27 (23.5%)", "0.00135", "0.118", "INOH"], ["nuclear receptors coordinate the activities of chromatin remodeling complexes and coactivators to facilitate initiation of transcription in carcinoma cells", "8", "5 (62.5%)", "0.00145", "0.118", "BioCarta"], ["Signaling by FGFR2", "273", "53 (19.4%)", "0.00148", "0.118", "Reactome"], ["Interleukin-3, 5 and GM-CSF signaling", "211", "43 (20.4%)", "0.00152", "0.118", "Reactome"], ["Downstream signaling of activated FGFR2", "267", "52 (19.5%)", "0.00152", "0.118", "Reactome"], ["Downstream signaling of activated FGFR1", "267", "52 (19.5%)", "0.00152", "0.118", "Reactome"], ["Downstream signaling of activated FGFR3", "267", "52 (19.5%)", "0.00152", "0.118", "Reactome"], ["Downstream signaling of activated FGFR4", "267", "52 (19.5%)", "0.00152", "0.118", "Reactome"], ["Signaling by FGFR", "274", "53 (19.3%)", "0.00161", "0.118", "Reactome"], ["Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human)", "83", "21 (25.3%)", "0.00167", "0.118", "KEGG"], ["Signaling by Insulin receptor", "262", "51 (19.5%)", "0.0017", "0.118", "Reactome"], ["Androgen receptor signaling pathway", "89", "22 (24.7%)", "0.00181", "0.118", "Wikipathways"], ["Signaling by NOTCH1", "73", "19 (26.0%)", "0.00191", "0.118", "Reactome"], ["Ectoderm Differentiation", "141", "31 (22.0%)", "0.00194", "0.118", "Wikipathways"], ["Signaling by ERBB2", "277", "53 (19.1%)", "0.00206", "0.118", "Reactome"], ["Interleukin-2 signaling", "202", "41 (20.3%)", "0.00209", "0.118", "Reactome"], ["HTLV-I infection - Homo sapiens (human)", "259", "50 (19.3%)", "0.00224", "0.118", "KEGG"], ["Arrhythmogenic Right Ventricular Cardiomyopathy", "74", "19 (25.7%)", "0.00227", "0.118", "Wikipathways"], ["Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human)", "74", "19 (25.7%)", "0.00227", "0.118", "KEGG"], ["Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants", "53", "15 (28.3%)", "0.0023", "0.118", "Reactome"], ["Constitutive Signaling by NOTCH1 PEST Domain Mutants", "53", "15 (28.3%)", "0.0023", "0.118", "Reactome"], ["Signaling by NOTCH1 PEST Domain Mutants in Cancer", "53", "15 (28.3%)", "0.0023", "0.118", "Reactome"], ["Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer", "53", "15 (28.3%)", "0.0023", "0.118", "Reactome"], ["Signaling by NOTCH1 in Cancer", "53", "15 (28.3%)", "0.0023", "0.118", "Reactome"], ["Platelet activation - Homo sapiens (human)", "131", "29 (22.1%)", "0.00239", "0.118", "KEGG"], ["Adipogenesis", "131", "29 (22.1%)", "0.00239", "0.118", "Wikipathways"], ["Downstream signal transduction", "279", "53 (19.0%)", "0.00242", "0.118", "Reactome"], ["Signaling by EGFR", "292", "55 (18.8%)", "0.00246", "0.118", "Reactome"], ["Regulation of nuclear beta catenin signaling and target gene transcription", "80", "20 (25.0%)", "0.00248", "0.118", "PID"], ["Validated nuclear estrogen receptor alpha network", "64", "17 (26.6%)", "0.00257", "0.118", "PID"], ["NCAM signaling for neurite out-growth", "223", "44 (19.7%)", "0.0026", "0.118", "Reactome"], ["Downstream signaling events of B Cell Receptor (BCR)", "120", "27 (22.5%)", "0.0026", "0.118", "Reactome"], ["BMP signaling Dro", "34", "11 (32.4%)", "0.00275", "0.122", "INOH"], ["Signaling by Leptin", "193", "39 (20.2%)", "0.00287", "0.124", "Reactome"], ["Inactivation of Cdc42 and Rac", "9", "5 (55.6%)", "0.00291", "0.124", "Reactome"], ["DAP12 signaling", "282", "53 (18.8%)", "0.00306", "0.129", "Reactome"], ["Mesodermal Commitment Pathway", "76", "19 (25.0%)", "0.00314", "0.129", "Wikipathways"], ["Insulin receptor signalling cascade", "238", "46 (19.3%)", "0.00321", "0.129", "Reactome"], ["regulation of pgc-1a", "21", "8 (38.1%)", "0.00332", "0.129", "BioCarta"], ["EPH-ephrin mediated repulsion of cells", "30", "10 (33.3%)", "0.00332", "0.129", "Reactome"], ["Retinoic acid receptors-mediated signaling", "30", "10 (33.3%)", "0.00332", "0.129", "PID"], ["FoxO signaling pathway - Homo sapiens (human)", "134", "29 (21.6%)", "0.0034", "0.13", "KEGG"], ["Interleukin receptor SHC signaling", "195", "39 (20.0%)", "0.00346", "0.13", "Reactome"], ["NGF signalling via TRKA from the plasma membrane", "310", "57 (18.4%)", "0.00361", "0.133", "Reactome"], ["NRAGE signals death through JNK", "45", "13 (28.9%)", "0.00363", "0.133", "Reactome"], ["Constitutive Signaling by Aberrant PI3K in Cancer", "61", "16 (26.2%)", "0.00389", "0.14", "Reactome"], ["AMPK signaling pathway - Homo sapiens (human)", "124", "27 (21.8%)", "0.00422", "0.148", "KEGG"], ["MAPK1/MAPK3 signaling", "191", "38 (19.9%)", "0.00424", "0.148", "Reactome"], ["Signaling by VEGF", "274", "51 (18.6%)", "0.00444", "0.149", "Reactome"], ["Wnt Signaling Pathway and Pluripotency", "101", "23 (22.8%)", "0.00445", "0.149", "Wikipathways"], ["VEGFR2 mediated cell proliferation", "198", "39 (19.7%)", "0.00455", "0.149", "Reactome"], ["FRS-mediated FGFR2 signaling", "186", "37 (19.9%)", "0.00475", "0.149", "Reactome"], ["FRS-mediated FGFR1 signaling", "186", "37 (19.9%)", "0.00475", "0.149", "Reactome"], ["FRS-mediated FGFR3 signaling", "186", "37 (19.9%)", "0.00475", "0.149", "Reactome"], ["FRS-mediated FGFR4 signaling", "186", "37 (19.9%)", "0.00475", "0.149", "Reactome"], ["Dilated cardiomyopathy - Homo sapiens (human)", "90", "21 (23.3%)", "0.00475", "0.149", "KEGG"], ["repression of WNT target genes", "10", "5 (50.0%)", "0.00519", "0.16", "Reactome"], ["MAPK family signaling cascades", "225", "43 (19.1%)", "0.00529", "0.16", "Reactome"], ["MAPK signaling pathway - Homo sapiens (human)", "257", "48 (18.7%)", "0.00529", "0.16", "KEGG"], ["transcription regulation by methyltransferase of carm1", "14", "6 (42.9%)", "0.00556", "0.16", "BioCarta"], ["Netrin-1 signaling", "37", "11 (29.7%)", "0.0057", "0.16", "Reactome"], ["IRS-related events triggered by IGF1R", "239", "45 (18.8%)", "0.00583", "0.16", "Reactome"], ["IGF1R signaling cascade", "239", "45 (18.8%)", "0.00583", "0.16", "Reactome"], ["Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)", "239", "45 (18.8%)", "0.00583", "0.16", "Reactome"], ["Neuronal System", "291", "53 (18.2%)", "0.00595", "0.16", "Reactome"], ["DAP12 interactions", "298", "54 (18.1%)", "0.00614", "0.16", "Reactome"], ["Gastric acid secretion - Homo sapiens (human)", "75", "18 (24.0%)", "0.00631", "0.16", "KEGG"], ["Fatty acid, triacylglycerol, and ketone body metabolism", "98", "22 (22.4%)", "0.00637", "0.16", "Reactome"], ["PIP3 activates AKT signaling", "98", "22 (22.4%)", "0.00637", "0.16", "Reactome"], ["PI-3K cascade:FGFR2", "98", "22 (22.4%)", "0.00637", "0.16", "Reactome"], ["PI-3K cascade:FGFR1", "98", "22 (22.4%)", "0.00637", "0.16", "Reactome"], ["PI-3K cascade:FGFR3", "98", "22 (22.4%)", "0.00637", "0.16", "Reactome"], ["PI-3K cascade:FGFR4", "98", "22 (22.4%)", "0.00637", "0.16", "Reactome"], ["PI3K events in ERBB4 signaling", "98", "22 (22.4%)", "0.00637", "0.16", "Reactome"], ["PI3K events in ERBB2 signaling", "98", "22 (22.4%)", "0.00637", "0.16", "Reactome"], ["VEGFA-VEGFR2 Pathway", "266", "49 (18.4%)", "0.00639", "0.16", "Reactome"], ["Collagen biosynthesis and modifying enzymes", "64", "16 (25.0%)", "0.00644", "0.16", "Reactome"], ["IRS-mediated signalling", "235", "44 (18.7%)", "0.00704", "0.173", "Reactome"], ["O-linked glycosylation", "105", "23 (21.9%)", "0.00731", "0.173", "Reactome"], ["RAF/MAP kinase cascade", "185", "36 (19.5%)", "0.00759", "0.173", "Reactome"], ["SHC1 events in EGFR signaling", "185", "36 (19.5%)", "0.00759", "0.173", "Reactome"], ["SOS-mediated signalling", "185", "36 (19.5%)", "0.00759", "0.173", "Reactome"], ["GRB2 events in EGFR signaling", "185", "36 (19.5%)", "0.00759", "0.173", "Reactome"], ["SHC1 events in ERBB2 signaling", "185", "36 (19.5%)", "0.00759", "0.173", "Reactome"], ["SHC1 events in ERBB4 signaling", "185", "36 (19.5%)", "0.00759", "0.173", "Reactome"], ["GRB2 events in ERBB2 signaling", "185", "36 (19.5%)", "0.00759", "0.173", "Reactome"], ["Regulation of Commissural axon pathfinding by Slit and Robo", "4", "3 (75.0%)", "0.00784", "0.175", "Reactome"], ["Fosphenytoin (Antiarrhythmic) Metabolism Pathway", "4", "3 (75.0%)", "0.00784", "0.175", "SMPDB"], ["Ephrin B reverse signaling", "24", "8 (33.3%)", "0.0084", "0.186", "PID"], ["Signaling by Interleukins", "270", "49 (18.1%)", "0.00851", "0.186", "Reactome"], ["Transport of organic anions", "11", "5 (45.5%)", "0.00852", "0.186", "Reactome"], ["Rho GTPase cycle", "125", "26 (20.8%)", "0.00914", "0.194", "Reactome"], ["PI3K/AKT activation", "101", "22 (21.8%)", "0.00918", "0.194", "Reactome"], ["Thyroid hormone signaling pathway - Homo sapiens (human)", "119", "25 (21.0%)", "0.0092", "0.194", "KEGG"], ["Signaling by NOTCH", "107", "23 (21.5%)", "0.00923", "0.194", "Reactome"], ["Cell death signalling via NRAGE, NRIF and NADE", "61", "15 (24.6%)", "0.0096", "0.2", "Reactome"]], "row_count": 120, "column_count": 6, "numeric_cells": 489, "header_rows": 1, "locator": "section[3]/table-wrap[2]#t0010"}}, {"id": "asset:table:pmid:29201983:5", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:e78853399a1c568de357199c8a538754a6fb4926905f7241b56431765a03fa06", "bytes": 3733, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[3]/table-wrap[3]#t0015", "version": null, "note": "Names and FCs of the 33 neighbors of the EntrezGene ID 2033 (see Fig. 1) after the exposure of PHHs for 5 days daily to VPA. PHHs, primary human hepatocytes; VPA, valproic acid; FCs, fold changes.", "structure": {"pmcid": "PMC5702865", "section_index": 3, "section_title": "Data", "row_count": 53, "column_count": 5}, "table": {"label": "Table 3", "caption": "Names and FCs of the 33 neighbors of the EntrezGene ID 2033 (see Fig. 1) after the exposure of PHHs for 5 days daily to VPA. PHHs, primary human hepatocytes; VPA, valproic acid; FCs, fold changes.", "rows": [["Entrez Gene ID", "Gene Symbol", "Gene Name", "MeDIP-seq FCs", "Steatosis-related pathway(s)"], ["354", "KLK3", "kallikrein-related peptidase 3", "1.9", "–"], ["595", "CCND1", "cyclin D1", "2.1", "–"], ["864", "RUNX3", "runt-related transcription factor 3", "2", "–"], ["", "", "", "", ""], ["1026", "CDKN1A", "cyclin-dependent kinase inhibitor 1 A (p21, Cip1)", "-3.5", "Adipogenesis"], ["Signaling events mediated by HDAC Class III"], ["", "", "", "", ""], ["1387", "CREBBP", "CREB binding protein", "-3.2", "Signaling events mediated by HDAC Class III"], ["Transcriptional regulation of white adipocyte differentiation"], ["Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)"], ["Signaling events mediated by HDAC Class I"], ["Fatty acid, triacylglycerol, and ketone body metabolism"], ["1488", "CTBP2", "C-terminal binding protein 2", "-3.9", "–"], ["1844", "DUSP2", "dual specificity phosphatase 2", "2.4", "–"], ["1958", "EGR1", "early growth response 1", "-3.6", "–"], ["", "", "", "", ""], ["2033", "EP300", "E1A binding protein p300", "-5.2", "Signaling events mediated by HDAC Class III"], ["Transcriptional regulation of white adipocyte differentiation"], ["Signaling events mediated by HDAC Class I"], ["2309", "FOXO3", "forkhead box O3", "2.2", "Signaling events mediated by HDAC Class III"], ["2353", "FOS", "FBJ murine osteosarcoma viral oncogene homolog", "-3.5", "–"], ["2626", "GATA4", "GATA binding protein 4", "2.5", "Adipogenesis"], ["4088", "SMAD3", "SMAD family member 3", "2.4", "Adipogenesis"], ["4205", "MEF2A", "myocyte enhancer factor 2 A", "2.2", "Adipogenesis"], ["4772", "NFATC1", "nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1", "1.8", "–"], ["5594", "MAPK1", "mitogen-activated protein kinase 1", "2.3", "–"], ["5914", "RARA", "retinoic acid receptor, alpha", "-3.8", "Adipogenesis"], ["6095", "RORA", "RAR-related orphan receptor A", "-4", "Adipogenesis"], ["", "", "", "", ""], ["6256", "RXRA", "retinoid X receptor, alpha", "-3.8", "Adipogenesis"], ["Transcriptional regulation of white adipocyte differentiation"], ["Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)"], ["Fatty acid, triacylglycerol, and ketone body metabolism"], ["6670", "SP3", "Sp3 transcription factor", "-4.1", "–"], ["6776", "STAT5A", "signal transducer and activator of transcription 5 A", "2.2", "Adipogenesis"], ["6925", "TCF4", "transcription factor 4", "-4", "–"], ["6929", "TCF3", "transcription factor 3", "2.1", "–"], ["6934", "TCF7L2", "transcription factor 7-like 2 (T-cell specific, HMG-box)", "-3.4", "–"], ["6938", "TCF12", "transcription factor 12", "2.12", "–"], ["7026", "NR2F2", "nuclear receptor subfamily 2, group F, member 2", "2.6", "–"], ["7161", "TP73", "tumor protein p73", "2.5", "–"], ["9252", "RPS6KA5", "ribosomal protein S6 kinase, 90 kDa, polypeptide 5", "-3.9", "–"], ["9314", "9314", "Kruppel-like factor 4 (gut)", "2.7", "–"], ["", "", "", "", ""], ["9611", "NCOR1", "nuclear receptor corepressor 1", "-3.4", "Adipogenesis"], ["Transcriptional regulation of white adipocyte differentiation"], ["Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)"], ["Signaling events mediated by HDAC Class I"], ["Fatty acid, triacylglycerol, and ketone body metabolism"], ["10365", "KLF2", "Kruppel-like factor 2", "-3.3", "Signaling events mediated by HDAC Class III"], ["23411", "SIRT1", "sirtuin 1", "-3.5", ""], ["90427", "BMF", "Bcl2 modifying facto", "2.2", ""]], "row_count": 53, "column_count": 5, "numeric_cells": 94, "header_rows": 1, "locator": "section[3]/table-wrap[3]#t0015"}}], "gaps": ["asset:data:geo:E-MTAB-4437 not downloaded", "asset:data:geo:E-MTAB-4437 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "edger", 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