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pmid:31346329

Integrated identification of key genes and pathways in Alzheimer's disease via comprehensive bioinformatical analyses.

Tingting Yan · Feng Ding · Yan Zhao

Hereditas · 2019 doi:10.1186/s41065-019-0101-0

Paper

complete

Experiment

complete

Data

partial

Analysis

complete

Execution

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title
Integrated identification of key genes and pathways in Alzheimer's disease via comprehensive bioinformatical analyses.
doi
10.1186/s41065-019-0101-0
pmid
31346329
authors array · 3 items
[0]
Tingting Yan
[1]
Feng Ding
[2]
Yan Zhao
journal
Hereditas
year
2019
abstract
BACKGROUND: Alzheimer's disease (AD) is known to be caused by multiple factors, meanwhile the pathogenic mechanism and development of AD associate closely with genetic factors. Existing understanding of the molecular mechanisms underlying AD remains incomplete. METHODS: Gene expression data (GSE48350) derived from post-modern brain was extracted from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were derived from hippocampus and entorhinal cortex regions between AD patients and healthy controls and detected via Morpheus. Functional enrichment analyses, including Gene Ontology (GO) and pathway analyses of DEGs, were performed via Cytoscape and followed by the construction of protein-protein interaction (PPI) network. Hub proteins were screened using the criteria: nodes degree≥10 (for hippocampus tissues) and ≥ 8 (for entorhinal cortex tissues). Molecular Complex Detection (MCODE) was used to filtrate the important clusters. University of California Santa Cruz (UCSC) and the database of RNA-binding protein specificities (RBPDB) were employed to identify the RNA-binding proteins of the long non-coding RNA (lncRNA). RESULTS: 251 & 74 genes were identified as DEGs, which consisted of 56 & 16 up-regulated genes and 195 & 58 down-regulated genes in hippocampus and entorhinal cortex, respectively. Biological analyses demonstrated that the biological processes and pathways related to memory, transmembrane transport, synaptic transmission, neuron survival, drug metabolism, ion homeostasis and signal transduction were enriched in these genes. 11 genes were identified as hub genes in hippocampus and entorhinal cortex, and 3 hub genes were identified as the novel candidates involved in the pathology of AD. Furthermore, 3 lncRNAs were filtrated, whose binding proteins were closely associated with AD. CONCLUSIONS: Through GO enrichment analyses, pathway analyses and PPI analyses, we showed a comprehensive interpretation of the pathogenesis of AD at a systematic biology level, and 3 novel candidate genes and 3 lncRNAs were identified as novel and potential candidates participating in the pathology of AD. The results of this study could supply integrated insights for understanding the pathogenic mechanism underlying AD and potential novel therapeutic targets.
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Alzheimer's Disease Dataset
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application/vnd.jats.table+json
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sha256:8ba44ff4929966e365ccc31596f39f4dd1602e6379f5c36ff074ebf746e74c62
bytes
981
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read_table
reader_status
available
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section[6]/table-wrap[3]#Tab4
version
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note
Pathway enrichment in Module 3
structure object · 5 fields
pmcid
PMC6636172
section_index
6
section_title
PPI network analyses and module analyses
row_count
5
column_count
6
table object · 8 fields
label
Table 4
caption
Pathway enrichment in Module 3
rows array · 5 items
[0] array · 6 items
[0]
#Pathway ID
[1]
Pathway description
[2]
Observed gene count
[3]
False discovery rate
[4]
Matching proteins in Your network (ids)
[5]
Matching Proteins In your Network (labels)
[1] array · 6 items
[0]
R-HSA:416476
[1]
G alpha (q) signaling events
[2]
5
[3]
3.80E-09
[4]
ENSP00000321106, ENSP00000324270, ENSP00000332225, ENSP00000369647, ENSP00000434045
[5]
AVP,GPR68, OXTR, PMCH, TAC1
[2] array · 6 items
[0]
R-HSA:373076
[1]
Class A/1 (Rhodopsin-like receptors)
[2]
5
[3]
1.49E-08
[4]
ENSP00000321106, ENSP00000324270, ENSP00000332225, ENSP00000369647, ENSP00000434045
[5]
AVP,GPR68, OXTR, PMCH, TAC1
[3] array · 6 items
[0]
R-HSA:375276
[1]
Peptide ligand-binding receptors
[2]
4
[3]
2.80E-07
[4]
ENSP00000321106, ENSP00000324270, ENSP00000332225, ENSP00000369647
[5]
AVP,OXTR, PMCH, TAC1
[4] array · 6 items
[0]
R-HSA:388479
[1]
Vasopressin-like receptors
[2]
2
[3]
5.84E-06
[4]
ENSP00000324270, ENSP00000369647
[5]
AVP,OXTR
locator
section[6]/table-wrap[3]#Tab4
[6] object · 16 fields
id
asset:table:pmid:31346329:5
role
table
format
jats-table
media_type
application/vnd.jats.table+json
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null
sha256
sha256:6bfe3c78f00bc5421f247b7859ccf4d67cb29f760070b01dc67f3e958b8c735b
bytes
1340
access
open
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verified
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read_table
reader_status
available
identifier
section[7]/table-wrap[1]#Tab5
version
null
note
Information of RNA-binding proteins of lncRNAs
structure object · 5 fields
pmcid
PMC6636172
section_index
7
section_title
Identification of lncRNAs and analysis of binding proteins
row_count
15
column_count
4
table object · 8 fields
label
Table 5
caption
Information of RNA-binding proteins of lncRNAs
rows array · 15 items
[0] array · 4 items
[0]
Gene symbol
[1]
Gene title
[2]
Involved cell functions
[3]
References
[1] array · 4 items
[0]
EIF4B
[1]
eukaryotic initiation factor 4B
[2]
long-term plastic changes in neuron
[3]
[34]
[2] array · 4 items
[0]
PABPC1
[1]
cytoplasmic poly(A)-binding protein 1
[2]
inflammation
[3]
[35]
[3] array · 4 items
[0]
FUS
[1]
fused in sarcoma
[2]
motor neuron degeneration
[3]
[36]
[4] array · 4 items
[0]
Pum2
[1]
pumilio 2
[2]
neurogenesis
[3]
[37]
[5] array · 4 items
[0]
MBNL1
[1]
muscleblind-like protein 1
[2]
neuron development
[3]
[38]
[6] array · 4 items
[0]
ACO1
[1]
aconitase 1
[2]
neuron mitochondrial function
[3]
[39]
[7] array · 4 items
[0]
KHSRP
[1]
KH-type splicing regulatory protein
[2]
inflammation, neuron survival and growth
[3]
[40]
[8] array · 4 items
[0]
YTHDC1
[1]
YTH domain-containing protein 1
[2]
neuron development
[3]
[41]
[9] array · 4 items
[0]
SFRS9
[1]
SR-family splicing factor 9
[2]
neuronal stimulation
[3]
[42]
[10] array · 4 items
[0]
RBMX
[1]
RNA binding motif protein X-linked gene
[2]
neuron development
[3]
[43]
[11] array · 4 items
[0]
SFRS13A
[1]
SR-family splicing factor 13A
[2]
cholesterol homeostasis, AD risk
[3]
[44]
[12] array · 4 items
[0]
KHDRBS3
[1]
KH RNA binding domain containing, signal transduction associated 3
[2]
cell proliferation
[3]
[45]
[13] array · 4 items
[0]
ELAVL1
[1]
ELAV-like protein 1
[2]
neurogenesis, neuroprotection
[3]
[46, 47]
[14] array · 4 items
[0]
SFRS1
[1]
SR-family splicing factor 1
[2]
neuron differentiation and survival
[3]
[48, 49]
locator
section[7]/table-wrap[1]#Tab5
[7] object · 16 fields
id
asset:table:pmid:31346329:6
role
table
format
jats-table
media_type
application/vnd.jats.table+json
uri
null
sha256
sha256:4a39f4633b36cdbf6c88157b50be539233b517f7abbc5082995a5ddaa2bbd5ac
bytes
1040
access
open
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verified
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read_table
reader_status
available
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section[8]/table-wrap[1]#Tab6
version
null
note
Detailed information of hub genes
structure object · 5 fields
pmcid
PMC6636172
section_index
8
section_title
Discussion
row_count
14
column_count
3
table object · 8 fields
label
Table 6
caption
Detailed information of hub genes
rows array · 14 items
[0] array · 3 items
[0]
Hub genes
[1]
Involved cell functions
[2]
References
[1] array · 1 item
[0]
Hippocampus
[2] array · 3 items
[0]
CDC42
[1]
actin cytoskeleton, gene expression, cell proliferation, Aβ neurotoxicity
[2]
[69–72]
[3] array · 3 items
[0]
VEGFA
[1]
neurogenesis, neuronal migration
[2]
[73–75]
[4] array · 3 items
[0]
BDNF
[1]
growth, survival and maintenance of neurons
[2]
[76, 77]
[5] array · 3 items
[0]
PDYN
[1]
memory, learning, and cognitive functions; drug consumption and addiction
[2]
[78–80]
[6] array · 3 items
[0]
CALB
[1]
long-term potentiation, synaptic plasticity, and memory functions
[2]
[81, 82]
[7] array · 3 items
[0]
TH
[1]
memory and recognition functions
[2]
[83, 84]
[8] array · 3 items
[0]
CACNA1A
[1]
learning and memory
[2]
[85, 86]
[9] array · 3 items
[0]
CD44
[1]
inflammation-related functions
[2]
[87–89]
[10] array · 3 items
[0]
TAC1
[1]
neurotrophic and inflammation related functions
[2]
[90, 91]
[11] array · 1 item
[0]
Entorhinal cortex
[12] array · 3 items
[0]
OXT
[1]
drug addiction, anxiety and memory formation
[2]
[92–94]
[13] array · 3 items
[0]
TAC1
[1]
neurotrophic and inflammation related functions
[2]
[90, 91]
locator
section[8]/table-wrap[1]#Tab6
gaps array · 2 items
[0]
asset:data:geo:GSE48350 not downloaded
[1]
asset:data:geo:GSE48350 licence not read
analysis object · 4 fields
state
complete
methods array · 2 items
[0] object · 10 fields
id
method-1
family
network_analysis
specific
ppi_network
label
Network / pathway analysis
dsl_operations array · 3 items
[0]
build_graph
[1]
centrality_scores
[2]
pathway_enrich
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
edge_list
evidence object · 3 fields
score
0.7
band
medium
quote
protein-protein interaction
[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
GO enrichment
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]
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 · 1 item
[0]
GSE48350
resolved_accessions array · 1 item
[0]
GSE48350
statements array · 1 item
[0]
All data generated or analyzed during this study are included in this published article [and its supplementary information files].
basis
The paper names GSE48350 in NCBI 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
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centrality_scores
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pathway_enrich
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source:pmid:31346329
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data:geo:GSE48350
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asset:table:pmid:31346329:1
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asset:table:pmid:31346329:2
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asset:table:pmid:31346329:3
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asset:table:pmid:31346329:4
[6]
asset:table:pmid:31346329:5
[7]
asset:table:pmid:31346329:6
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:GSE48350
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
2026-10-31T18:15:34Z
independence
single_reader
evidence_check object · 2 fields
method
null
availability
verbatim
calls
3
usage object · 3 fields
prompt_tokens
45993
completion_tokens
1158
cached_tokens
15624
stages array · 1 item
[0] object · 4 fields
id
extraction
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complete
reader
MiniMax-M3.1-Flash
provider
minimax
gaps array · 3 items
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review.independent_reader
[1]
review.machine_critique
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review.human_critique
execution object · 5 fields
state
absent
status
not_run
mode
null
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gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
[0] object · 3 fields
id
pmid:31346329
type
paper
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pmid:31346329
[1] object · 3 fields
id
source:pmid:31346329
type
manuscript
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PMID 31346329 full text
[2] object · 3 fields
id
data:geo:GSE48350
type
dataset
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GEO GSE48350
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activity-reading-sci-2026-11-01
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classification
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pmid:31346329
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pmid:31346329
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source:pmid:31346329
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PMID 31346329 full text
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data:geo:GSE48350
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dataset
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GEO GSE48350
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agent:corpus-assay-engine
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id
activity-read-31346329
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extraction
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source:pmid:31346329
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agent:minimax-reader
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activity-resolve-GSE48350
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agent:corpus-assay-engine
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agent:minimax-reader
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MiniMax literature reader
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pmid:31346329
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asset:data:geo:GSE48350 licence not read
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:31346329", "kind": "science-record", "revision": 7, "content_hash": "sha256:3943d3ec311b108d60af5360bd401432aa3fdcd30db3a9b01727f8ec6ef59bc7", "created_at": "2026-11-01T15:40:47Z", "updated_at": "2026-11-01T22:00:44Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrated identification of key genes and pathways in Alzheimer's disease via comprehensive bioinformatical analyses.", "doi": "10.1186/s41065-019-0101-0", "pmid": "31346329", "authors": ["Tingting Yan", "Feng Ding", "Yan Zhao"], "journal": "Hereditas", "year": 2019, "abstract": "BACKGROUND: Alzheimer's disease (AD) is known to be caused by multiple factors, meanwhile the pathogenic mechanism and development of AD associate closely with genetic factors. Existing understanding of the molecular mechanisms underlying AD remains incomplete.\nMETHODS: Gene expression data (GSE48350) derived from post-modern brain was extracted from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were derived from hippocampus and entorhinal cortex regions between AD patients and healthy controls and detected via Morpheus. Functional enrichment analyses, including Gene Ontology (GO) and pathway analyses of DEGs, were performed via Cytoscape and followed by the construction of protein-protein interaction (PPI) network. Hub proteins were screened using the criteria: nodes degree≥10 (for hippocampus tissues) and ≥ 8 (for entorhinal cortex tissues). Molecular Complex Detection (MCODE) was used to filtrate the important clusters. University of California Santa Cruz (UCSC) and the database of RNA-binding protein specificities (RBPDB) were employed to identify the RNA-binding proteins of the long non-coding RNA (lncRNA).\nRESULTS: 251 & 74 genes were identified as DEGs, which consisted of 56 & 16 up-regulated genes and 195 & 58 down-regulated genes in hippocampus and entorhinal cortex, respectively. Biological analyses demonstrated that the biological processes and pathways related to memory, transmembrane transport, synaptic transmission, neuron survival, drug metabolism, ion homeostasis and signal transduction were enriched in these genes. 11 genes were identified as hub genes in hippocampus and entorhinal cortex, and 3 hub genes were identified as the novel candidates involved in the pathology of AD. Furthermore, 3 lncRNAs were filtrated, whose binding proteins were closely associated with AD.\nCONCLUSIONS: Through GO enrichment analyses, pathway analyses and PPI analyses, we showed a comprehensive interpretation of the pathogenesis of AD at a systematic biology level, and 3 novel candidate genes and 3 lncRNAs were identified as novel and potential candidates participating in the pathology of AD. The results of this study could supply integrated insights for understanding the pathogenic mechanism underlying AD and potential novel therapeutic targets.", "claims": [{"id": "claim-data-access", "statement": "All data generated or analyzed during this study are included in this published article [and its supplementary information files].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31346329", "locator": "sections[21] \"Availability of data and materials\" paragraph 2", "quote": "All data generated or analyzed during this study are included in this published article [and its supplementary information files]."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:31346329"], "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:GSE48350"], "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:GSE48350"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:31346329", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s41065-019-0101-0", "sha256": "sha256:046264978612ca0bf0b866e2211d37cb9fdee6d1e34a344bb933a50d7b08cf43", "bytes": 55445, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s41065-019-0101-0", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6636172", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE48350", "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=GSE48350", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE48350", "version": null, "note": "All data generated or analyzed during this study are included in this published article [and its supplementary information files].", 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"sha256:c0a5d03f0fe28a6c901239427098ecdafae8825e715e041c728bb5c861f9298d", "bytes": 599, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[6]/table-wrap[2]#Tab3", "version": null, "note": "Pathway enrichment in Module 2", "structure": {"pmcid": "PMC6636172", "section_index": 6, "section_title": "PPI network analyses and module analyses", "row_count": 3, "column_count": 6}, "table": {"label": "Table 3", "caption": "Pathway enrichment in Module 2", "rows": [["#Pathway ID", "Pathway description", "Observed gene count", "False discovery rate", "Matching proteins in Your network (ids)", "Matching Proteins In your Network (labels)"], ["4080", "Neuroactive ligand- receptor interaction", "4", "0.00166", "ENSP00000234371, ENSP00000265572, ENSP00000350198, ENSP00000358511", "CNR1, KISS1R, OPRK1, SSTR2"], ["5030", "Cocaine addiction", "2", "0.0359", "ENSP00000370571, ENSP00000414303", "BDNF,TH"]], "row_count": 3, "column_count": 6, 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"verified", "reader": "read_table", "reader_status": "available", "identifier": "section[7]/table-wrap[1]#Tab5", "version": null, "note": "Information of RNA-binding proteins of lncRNAs", "structure": {"pmcid": "PMC6636172", "section_index": 7, "section_title": "Identification of lncRNAs and analysis of binding proteins", "row_count": 15, "column_count": 4}, "table": {"label": "Table 5", "caption": "Information of RNA-binding proteins of lncRNAs", "rows": [["Gene symbol", "Gene title", "Involved cell functions", "References"], ["EIF4B", "eukaryotic initiation factor 4B", "long-term plastic changes in neuron", "[34]"], ["PABPC1", "cytoplasmic poly(A)-binding protein 1", "inflammation", "[35]"], ["FUS", "fused in sarcoma", "motor neuron degeneration", "[36]"], ["Pum2", "pumilio 2", "neurogenesis", "[37]"], ["MBNL1", "muscleblind-like protein 1", "neuron development", "[38]"], ["ACO1", "aconitase 1", "neuron mitochondrial function", "[39]"], ["KHSRP", "KH-type splicing regulatory protein", "inflammation, neuron survival and growth", "[40]"], ["YTHDC1", "YTH domain-containing protein 1", "neuron development", "[41]"], ["SFRS9", "SR-family splicing factor 9", "neuronal stimulation", "[42]"], ["RBMX", "RNA binding motif protein X-linked gene", "neuron development", "[43]"], ["SFRS13A", "SR-family splicing factor 13A", "cholesterol homeostasis, AD risk", "[44]"], ["KHDRBS3", "KH RNA binding domain containing, signal transduction associated 3", "cell proliferation", "[45]"], ["ELAVL1", "ELAV-like protein 1", "neurogenesis, neuroprotection", "[46, 47]"], ["SFRS1", "SR-family splicing factor 1", "neuron differentiation and survival", "[48, 49]"]], "row_count": 15, "column_count": 4, "numeric_cells": 26, "header_rows": 1, "locator": "section[7]/table-wrap[1]#Tab5"}}, {"id": "asset:table:pmid:31346329:6", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": 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