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pmid:31481902

Identification of Hub Genes and Key Pathways Associated With Bipolar Disorder Based on Weighted Gene Co-expression Network Analysis.

Yang Liu · Hui-Yun Gu · Jie Zhu · Yu-Ming Niu · Chao Zhang · Guang-Ling Guo

Frontiers in physiology · 2019 doi:10.3389/fphys.2019.01081

Paper

complete

Experiment

complete

Data

partial

Analysis

partial

Execution

absent

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pmid:31481902
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science-record
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2026-11-01T15:40:49Z
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2026-11-01T22:00:48Z
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paper object · 10 fields
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title
Identification of Hub Genes and Key Pathways Associated With Bipolar Disorder Based on Weighted Gene Co-expression Network Analysis.
doi
10.3389/fphys.2019.01081
pmid
31481902
authors array · 6 items
[0]
Yang Liu
[1]
Hui-Yun Gu
[2]
Jie Zhu
[3]
Yu-Ming Niu
[4]
Chao Zhang
[5]
Guang-Ling Guo
journal
Frontiers in physiology
year
2019
abstract
Bipolar disorder (BD) is a complex mental disorder with high mortality and disability rates worldwide; however, research on its pathogenesis and diagnostic methods remains limited. This study aimed to elucidate potential candidate hub genes and key pathways related to BD in a pre-frontal cortex sample. Raw gene expression profile files of GSE53987, including 36 samples, were obtained from the gene expression omnibus (GEO) database. After data pre-processing, 10,094 genes were selected for weighted gene co-expression network analysis (WGCNA). After dividing highly related genes into 19 modules, we found that the pink, midnight blue, and brown modules were highly correlated with BD. Functional annotation and pathway enrichment analysis for modules, which indicated some key pathways, were conducted based on the Enrichr database. One of the most remarkable significant pathways is the Hippo signaling pathway and its positive transcriptional regulation. Finally, 30 hub genes were identified in three modules. Hub genes with a high degree of connectivity in the PPI network are significantly enriched in positive regulation of transcription. In addition, the hub genes were validated based on another dataset (GSE12649). Taken together, the identification of these 30 hub genes and enrichment pathways might have important clinical implications for BD treatment and diagnosis.
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Weighted gene co-expression network analysis package was necessary for the co-expression network construction (Langfelder and Horvath, 2008).
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methodological
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sections[4] "Co-expression Network Construction" paragraph 2
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Weighted gene co-expression network analysis package was necessary for the co-expression network construction (Langfelder and Horvath, 2008).
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Publicly available datasets were analyzed in this study. This data can be found at: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE53987.
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sections[13] "Data Availability" paragraph 2
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Publicly available datasets were analyzed in this study. This data can be found at: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE53987.
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Publicly available datasets were analyzed in this study. This data can be found at: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE53987.
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96
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Homo sapiens
title
Gene expression from human prefrontal cortex (BA46)
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2026-11-01T15:39:54Z
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Publicly available datasets were analyzed in this study. This data can be found at: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE53987.
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GEO
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Publicly available datasets were analyzed in this study. This data can be found at: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE53987.
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GSM1304868
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GSM1304870
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GSM1304871
[20]
GSM1304872
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GSM1304873
[22]
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[23]
GSM1304875
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GSM1304876
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GSM1304877
[26]
GSM1304878
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GSM1304879
[28]
GSM1304880
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GSM1304881
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GSM1304882
[31]
GSM1304883
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GSM1304884
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GSM1304885
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GSM1304886
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GSM1304888
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GSM1304896
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GSM1304897
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GSM1304899
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GSM1304900
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GSM1304901
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GSM1304902
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GSM1304907
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GSM1304908
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GSM1304909
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GSM1304910
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GSM1304911
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GSM1304912
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GSM1304913
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GSM1304914
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GSM1304915
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GSM1304916
[65]
GSM1304917
[66]
GSM1304918
[67]
GSM1304919
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GSM1304920
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GSM1304921
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GSM1304922
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GSM1304923
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GSM1304924
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GSM1304925
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GSM1304926
[75]
GSM1304927
[76]
GSM1304928
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GSM1304929
[78]
GSM1304930
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GSM1304931
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GSM1304932
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[86]
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GSM1304939
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GSM1304960
[109]
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[110]
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sample_count
205
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null
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570
taxon
Homo sapiens
title
Microarray profiling of PFC, HPC and STR from subjects with schizophrenia, bipolar, MDD or control
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[3] object · 16 fields
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Hub genes from the interesting modules.
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pmcid
PMC6710482
section_index
10
section_title
Validation of Hub Gene and PPI Network Construction
row_count
31
column_count
6
table object · 8 fields
label
TABLE 1
caption
Hub genes from the interesting modules.
rows array · 31 items
[0] array · 6 items
[0]
Gene symbol
[1]
ENTREZ_GENE_ID
[2]
Gene ontology
[3]
geneModuleMembership
[4]
Gene trait significance
[5]
Up or down
[1] array · 6 items
[0]
AGT
[1]
183
[2]
Alkylguanine DNA binding
[3]
0.887157454
[4]
0.298842057
[5]
Down
[2] array · 6 items
[0]
AHCYL1
[1]
10768
[2]
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[3]
0.892921034
[4]
0.263587391
[5]
Down
[3] array · 6 items
[0]
APOE
[1]
348
[2]
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[3]
0.906508824
[4]
0.259473598
[5]
Down
[4] array · 6 items
[0]
ATP1A2
[1]
477
[2]
Temperature gated cation channel activity
[3]
0.944732073
[4]
0.358469425
[5]
Down
[5] array · 6 items
[0]
CHRDL1
[1]
91851
[2]
Negative regulation of secondary growth
[3]
0.863182953
[4]
0.462817741
[5]
Down
[6] array · 6 items
[0]
EMX2
[1]
2018
[2]
Forebrain neuroblast differentiation
[3]
0.943545349
[4]
0.339285953
[5]
Down
[7] array · 6 items
[0]
ETNPPL
[1]
64850
[2]
/
[3]
0.905878301
[4]
0.312454124
[5]
Down
[8] array · 6 items
[0]
FAM189A2
[1]
9413
[2]
Gene expression
[3]
0.872771128
[4]
0.313792924
[5]
Down
[9] array · 6 items
[0]
FGF2
[1]
2247
[2]
fibroblast proliferation
[3]
0.9348346
[4]
0.45704696
[5]
Down
[10] array · 6 items
[0]
GJA1
[1]
2697
[2]
Gap junction
[3]
0.920113458
[4]
0.328482543
[5]
Down
[11] array · 6 items
[0]
GNA12
[1]
2768
[2]
Spermatid nucleus differentiation
[3]
0.867055073
[4]
0.311316484
[5]
Down
[12] array · 6 items
[0]
HEPH
[1]
9843
[2]
Copper exporting atpase activity
[3]
0.959262811
[4]
0.384839787
[5]
Down
[13] array · 6 items
[0]
IL17RB
[1]
55540
[2]
Cardiac fibroblast cell fate commitment
[3]
0.87323481
[4]
0.315545635
[5]
Down
[14] array · 6 items
[0]
MAOA
[1]
4128
[2]
Monoamine oxidase activity
[3]
0.889016805
[4]
0.495684
[5]
Down
[15] array · 6 items
[0]
METTL7A
[1]
25840
[2]
RNA polymerase II regulatory region DNA binding
[3]
0.93466073
[4]
0.322509631
[5]
Down
[16] array · 6 items
[0]
NOTCH2
[1]
4853
[2]
Notch signaling pathway
[3]
0.952637565
[4]
0.360026782
[5]
Down
[17] array · 6 items
[0]
NTRK2
[1]
4915
[2]
Regulation of neurotrophin TRK receptor signaling pathway
[3]
0.947485184
[4]
0.327326464
[5]
Down
[18] array · 6 items
[0]
PARD3
[1]
56288
[2]
Positive regulation of JAK STAT cascade
[3]
0.877332438
[4]
0.357811988
[5]
Down
[19] array · 6 items
[0]
PAX6
[1]
5080
[2]
Eye development
[3]
0.912624234
[4]
0.408751454
[5]
Down
[20] array · 6 items
[0]
PDLIM5
[1]
10611
[2]
Activation of bipolar cell growth
[3]
0.92796358
[4]
0.456391993
[5]
Down
[21] array · 6 items
[0]
PPAP2B
[1]
8613
[2]
Cell migration involved in coronary angiogenesis
[3]
0.882924502
[4]
0.299775962
[5]
Down
[22] array · 6 items
[0]
RAB31
[1]
11031
[2]
ER body
[3]
0.908780797
[4]
0.376400336
[5]
Down
[23] array · 6 items
[0]
SDC2
[1]
6383
[2]
Positive regulation of synapse maturation
[3]
0.935916785
[4]
0.333198546
[5]
Down
[24] array · 6 items
[0]
SDC4
[1]
6385
[2]
Small molecule catabolic process
[3]
0.889206651
[4]
0.361762932
[5]
Down
[25] array · 6 items
[0]
SLC1A3
[1]
6507
[2]
Negative regulation of L glutamate transport
[3]
0.930712467
[4]
0.322178332
[5]
Down
[26] array · 6 items
[0]
SMAD2
[1]
4087
[2]
SMAD2 protein complex
[3]
0.841744744
[4]
0.431128371
[5]
Down
[27] array · 6 items
[0]
SOX2
[1]
6657
[2]
Stem cell differentiation
[3]
0.960030288
[4]
0.437884345
[5]
Down
[28] array · 6 items
[0]
TP53BP2
[1]
7159
[2]
P53 binding
[3]
0.916365941
[4]
0.261334186
[5]
Down
[29] array · 6 items
[0]
YAP1
[1]
10413
[2]
Hippo signaling
[3]
0.946460117
[4]
0.317467764
[5]
Down
[30] array · 6 items
[0]
YES1
[1]
7525
[2]
Regulation of B cell antigen processing and presentation
[3]
0.913582422
[4]
0.40331199
[5]
Down
locator
section[10]/table-wrap[1]#T1
gaps array · 4 items
[0]
asset:data:geo:GSE12649 not downloaded
[1]
asset:data:geo:GSE12649 licence not read
[2]
asset:data:geo:GSE53987 not downloaded
[3]
asset:data:geo:GSE53987 licence not read
analysis object · 4 fields
state
partial
methods array · 3 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
network_analysis
specific
pathway_enrichment
label
Network / pathway analysis
dsl_operations array · 1 item
[0]
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
pathway enrichment
[2] object · 10 fields
id
method-3
family
null
specific
null
label
Weighted gene co-expression network analysis (WGCNA)
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
Weighted gene co-expression network analysis package was necessary for the co-expression network construction (Langfelder and Horvath, 2008).
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]
GSE53987
[1]
GSE12649
resolved_accessions array · 2 items
[0]
GSE53987
[1]
GSE12649
statements array · 1 item
[0]
Publicly available datasets were analyzed in this study. This data can be found at: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE53987.
basis
The paper names GSE53987, GSE12649 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
can_run object · 3 fields
dsl_operations array · 3 items
[0]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
assets array · 3 items
[0]
source:pmid:31481902
[1]
data:geo:GSE12649
[2]
asset:table:pmid:31481902:1
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:GSE12649
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
2026-10-31T18:16:00Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
19249
completion_tokens
1656
cached_tokens
12544
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:31481902
type
paper
label
pmid:31481902
[1] object · 3 fields
id
source:pmid:31481902
type
manuscript
label
PMID 31481902 full text
[2] object · 3 fields
id
data:geo:GSE12649
type
dataset
label
GEO GSE12649
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:31481902
type
paper
label
pmid:31481902
[1] object · 3 fields
id
source:pmid:31481902
type
manuscript
label
PMID 31481902 full text
[2] object · 3 fields
id
data:geo:GSE12649
type
dataset
label
GEO GSE12649
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-31481902
type
extraction
used array · 1 item
[0]
source:pmid:31481902
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE12649
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE12649
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:31481902
parent_hash
sha256:594a49c0f6d1de449d4b67a30e7222697e49f119e2cae218059b6f30dac1db09
fork_of
null
gaps array · 9 items
[0]
asset:data:geo:GSE12649 licence not read
[1]
asset:data:geo:GSE12649 not downloaded
[2]
asset:data:geo:GSE53987 licence not read
[3]
asset:data:geo:GSE53987 not downloaded
[4]
execution.not_run
[5]
method.reader_named_unmapped
[6]
review.human_critique
[7]
review.independent_reader
[8]
review.machine_critique
assays array · 1 item
[0] object · 11 fields
role
analysis
definition_id
network_analysis
definition_version
f2132e96ae6c7a4e
required_operations array · 3 items
[0]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
support_state
supported
source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
PPI
order_basis
analysis_only
id
assay:1
Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31481902", "kind": "science-record", "revision": 5, "content_hash": "sha256:fa0abe9afd7a6bec1cad1b70632fb04873c3224060031ae500adba06f6ccfe61", "created_at": "2026-11-01T15:40:49Z", "updated_at": "2026-11-01T22:00:48Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Hub Genes and Key Pathways Associated With Bipolar Disorder Based on Weighted Gene Co-expression Network Analysis.", "doi": "10.3389/fphys.2019.01081", "pmid": "31481902", "authors": ["Yang Liu", "Hui-Yun Gu", "Jie Zhu", "Yu-Ming Niu", "Chao Zhang", "Guang-Ling Guo"], "journal": "Frontiers in physiology", "year": 2019, "abstract": "Bipolar disorder (BD) is a complex mental disorder with high mortality and disability rates worldwide; however, research on its pathogenesis and diagnostic methods remains limited. This study aimed to elucidate potential candidate hub genes and key pathways related to BD in a pre-frontal cortex sample. Raw gene expression profile files of GSE53987, including 36 samples, were obtained from the gene expression omnibus (GEO) database. After data pre-processing, 10,094 genes were selected for weighted gene co-expression network analysis (WGCNA). After dividing highly related genes into 19 modules, we found that the pink, midnight blue, and brown modules were highly correlated with BD. Functional annotation and pathway enrichment analysis for modules, which indicated some key pathways, were conducted based on the Enrichr database. One of the most remarkable significant pathways is the Hippo signaling pathway and its positive transcriptional regulation. Finally, 30 hub genes were identified in three modules. Hub genes with a high degree of connectivity in the PPI network are significantly enriched in positive regulation of transcription. In addition, the hub genes were validated based on another dataset (GSE12649). Taken together, the identification of these 30 hub genes and enrichment pathways might have important clinical implications for BD treatment and diagnosis.", "claims": [{"id": "claim-method", "statement": "Weighted gene co-expression network analysis package was necessary for the co-expression network construction (Langfelder and Horvath, 2008).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31481902", "locator": "sections[4] \"Co-expression Network Construction\" paragraph 2", "quote": "Weighted gene co-expression network analysis package was necessary for the co-expression network construction (Langfelder and Horvath, 2008)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. 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This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE12649"], "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:GSE12649"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31481902", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fphys.2019.01081", "sha256": "sha256:be56553b04c4d1d981ed19bec509192a3e886d8e335252664a9c7b53d24f7e35", "bytes": 25924, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fphys.2019.01081", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6710482", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE12649", "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=GSE12649", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE12649", "version": null, "note": "Publicly available datasets were analyzed in this study. This data can be found at: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE53987.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. This data can be found at: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE53987.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM317385", "GSM317386", "GSM317387", "GSM317388", "GSM317389", "GSM317390", "GSM317391", "GSM317392", "GSM317393", "GSM317394", "GSM317395", "GSM317396", "GSM317397", "GSM317398", "GSM317399", "GSM317400", "GSM317401", "GSM317402", "GSM317403", "GSM317404", "GSM317405", "GSM317406", "GSM317407", "GSM317408", "GSM317409", "GSM317410", "GSM317411", "GSM317412", "GSM317413", "GSM317414", "GSM317415", "GSM317416", "GSM317417", "GSM317418", "GSM317419", "GSM317420", "GSM317421", "GSM317422", "GSM317423", "GSM317424", "GSM317425", "GSM317426", "GSM317427", "GSM317428", "GSM317429", "GSM317430", "GSM317431", "GSM317432", "GSM317433", "GSM317434", "GSM317435", "GSM317436", "GSM317437", "GSM317438", "GSM317439", "GSM317440", "GSM317441", "GSM317442", "GSM317443", "GSM317444", "GSM317445", "GSM317446", "GSM317447", "GSM317448", "GSM317449", "GSM317450", "GSM317451", "GSM317452", "GSM317453", "GSM317454", "GSM317455", "GSM317456", "GSM317457", "GSM317458", "GSM317459", "GSM317460", "GSM317461", "GSM317462", "GSM317463", "GSM317464", "GSM317465", "GSM317466", "GSM317467", "GSM317468", "GSM317469", "GSM317470", "GSM317471", "GSM317472", "GSM317473", "GSM317474", "GSM317475", "GSM317476", "GSM317477", "GSM317478", "GSM317479", "GSM317480", "GSM317481", "GSM317482", "GSM317483", "GSM317484", "GSM317485", "GSM317486"], "sample_count": 102, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Gene expression from human prefrontal cortex (BA46)", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE53987", "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=GSE53987", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE53987", "version": null, "note": "Publicly available datasets were analyzed in this study. 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