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pmid:37549144

Influence of N6-methyladenosine (m6A) modification on cell phenotype in Alzheimer's disease.

Pengyun Ni · Kaiting Pan · Bingbing Zhao

PloS one · 2023 doi:10.1371/journal.pone.0289068

Paper

complete

Experiment

complete

Data

partial

Analysis

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title
Influence of N6-methyladenosine (m6A) modification on cell phenotype in Alzheimer's disease.
doi
10.1371/journal.pone.0289068
pmid
37549144
authors array · 3 items
[0]
Pengyun Ni
[1]
Kaiting Pan
[2]
Bingbing Zhao
journal
PloS one
year
2023
abstract
OBJECTIVE: Recent research has suggested that m6A modification takes on critical significance to Neurodegeneration. As indicated by the genome-wide map of m6A mRNA, genes in Alzheimer's disease model achieved significant m6A methylation. This study aimed to investigate the hub gene and pathway of m6A modification in the pathogenesis of AD. Moreover, possible brain regions with higher gene expression levels and compounds exerting potential therapeutic effects were identified. Thus, this study can provide a novel idea to explore the treatment of AD. METHODS: Differential expression genes (DEGs) of GSE5281 and GSE48350 from the Gene Expression Omnibus (GEO) database were screened using the Limma package. Next, the enrichment analysis was conducted on the screened DEGs. Moreover, the functional annotation was given for N6-methyladenosine (m6A) modification gene. The protein-protein interaction network (PPI) analysis and the visualization analysis were conducted using STRING and Cytoscape. The hub gene was identified using CytoHubba. The expression levels of Hub genes in different regions of brain tissue were analyzed based on Human Protein Atlas (HPA) database and Bgee database. Subsequently, the candidate drugs targeting hub genes were screened using cMAP. RESULTS: A total of 42 m6A modified genes were identified in AD (20 up-regulated and 22 down-regulated genes). The above-described genes played a certain role in biological processes (e.g., retinoic acid, DNA damage response and cysteine-type endopeptidase activity), cellular components (e.g., mitochondrial protein complex), and molecular functions (e.g., RNA methyltransferase activity and ubiquitin protein ligase). KEGG results suggested that the above-mentioned genes were primarily involved in the Hippo signaling pathway of neurodegeneration disease. A total of 10 hub genes were screened using the protein-protein interaction network, and the expression of hub genes in different regions of human brain was studied. Furthermore, 10 compounds with potential therapeutic effects on AD were predicted. CONCLUSION: This study revealed the potential role of the m6A modification gene in Alzheimer's disease through the bioinformatics analysis. The biological changes may be correlated with retinoic acid, DNA damage response and cysteine-type endopeptidase activity, which may occur through Hippo signaling pathway. The hub genes (SOX2, KLF4, ITGB4, CD44, MSX1, YAP1, AQP1, EGR2, YWHAZ and TFAP2C) and potential drugs may provide novel research directions for future prognosis and precise treatment.
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Subsequently, Limma package [25] was adopted to analyze the difference between the two groups.
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sections[4] "Analysis of differentially expressed genes (DEGs)" paragraph 2
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Subsequently, Limma package [25] was adopted to analyze the difference between the two groups.
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Two microarray datasets (GSE5281 and GSE48350) were downloaded in this study from the Gene Expression Omnibus (GEO) database [23] (http://www.ncbi.nlm.nih.gov/gds/) investigating gene expression profiles changes in patients with Alzheimer’s disease.
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sections[3] "Data acquisition and processing" paragraph 2
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Two microarray datasets (GSE5281 and GSE48350) were downloaded in this study from the Gene Expression Omnibus (GEO) database [23] (http://www.ncbi.nlm.nih.gov/gds/) investigating gene expression profiles changes in patients with Alzheimer’s disease.
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With the Limma package for differential expression analysis, with |log2(Fold Change)| > 0.58 and P.value < 0.05 as the screening conditions, 917 differently expressed genes in brain tissues of AD patients were identified, as compared with normal brain tissues.
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sections[12] "Identification of DEGs during AD" paragraph 2
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With the Limma package for differential expression analysis, with |log2(Fold Change)| > 0.58 and P.value < 0.05 as the screening conditions, 917 differently expressed genes in brain tissues of AD patients were identified, as compared with normal brain tissues.
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With the Limma package for differential expression analysis, with |log2(Fold Change)| > 0.58 and P.value < 0.05 as the screening conditions, 917 differently expressed genes in brain tissues of AD patients were identified, as compared with normal brain tissues.
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asset:data:geo:GSE5281 licence not read
analysis object · 4 fields
state
complete
methods array · 2 items
[0] object · 10 fields
id
method-1
family
differential_expression
specific
limma_voom
label
Differential expression analysis
dsl_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
count_matrix_with_condition
evidence object · 3 fields
score
1
band
verbatim
quote
Subsequently, Limma package [25] was adopted to analyze the difference between the two groups.
[1] object · 10 fields
id
method-2
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
targets array · 0 items
gaps array · 0 items
capability object · 3 fields
state
complete
requirements array · 1 item
[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
meta_analysis
[1]
machine_learning
[2]
survival_analysis
[3]
statistical_regression
[4]
pca
[5]
molecular_docking
[6]
network_analysis
[7]
differential_expression
[8]
gwas
candidate
Automated Assays Laravel application and simulated adapters
gaps array · 0 items
readiness object · 8 fields
state
complete
tier
R1
blocked_on
nothing:replicable_now
axes object · 3 fields
method object · 5 fields
tier
R1
expressible
true
required_operations array · 3 items
[0]
normalise_counts
[1]
differential_expression_fit
[2]
fdr_bh
missing_operations array · 0 items
basis
The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom.
capability object · 4 fields
tier
R1
capability_id
capability:computational_analysis
availability_state
owned
basis
The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here.
data object · 6 fields
tier
R1
reachable
true
accessions array · 2 items
[0]
GSE5281
[1]
GSE48350
resolved_accessions array · 2 items
[0]
GSE5281
[1]
GSE48350
statements array · 1 item
[0]
Two microarray datasets (GSE5281 and GSE48350) were downloaded in this study from the Gene Expression Omnibus (GEO) database [23] (http://www.ncbi.nlm.nih.gov/gds/) investigating gene expression profiles changes in patients with Alzheimer’s disease.
basis
The paper names GSE5281, GSE48350 in Gene Expression Omnibus (GEO) database 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 · 2 items
[0]
source:pmid:37549144
[1]
data:geo:GSE48350
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
2026-11-01T18:48:58Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
null
calls
5
usage object · 3 fields
prompt_tokens
8787
completion_tokens
1047
cached_tokens
264
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:37549144
type
paper
label
pmid:37549144
[1] object · 3 fields
id
source:pmid:37549144
type
manuscript
label
PMID 37549144 full text
[2] object · 3 fields
id
data:geo:GSE48350
type
dataset
label
GEO GSE48350
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:37549144
type
paper
label
pmid:37549144
[1] object · 3 fields
id
source:pmid:37549144
type
manuscript
label
PMID 37549144 full text
[2] object · 3 fields
id
data:geo:GSE48350
type
dataset
label
GEO GSE48350
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-37549144
type
extraction
used array · 1 item
[0]
source:pmid:37549144
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE48350
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE48350
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:37549144
parent_hash
sha256:8129bf58cede800032d1850a3da5fe644d13742311ae1c9428f02dfc59d90e45
fork_of
null
gaps array · 8 items
[0]
asset:data:geo:GSE48350 licence not read
[1]
asset:data:geo:GSE48350 not downloaded
[2]
asset:data:geo:GSE5281 licence not read
[3]
asset:data:geo:GSE5281 not downloaded
[4]
execution.not_run
[5]
review.human_critique
[6]
review.independent_reader
[7]
review.machine_critique
assays array · 1 item
[0] 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]
Subsequently, Limma package [25] was adopted to analyze the difference between the two groups.
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:37549144", "kind": "science-record", "revision": 4, "content_hash": "sha256:d785a2a4f81917857b0b8549bff0d9f04940825bf567b54f1e10713248fc40ff", "created_at": "2026-11-01T19:02:19Z", "updated_at": "2026-11-01T22:52:28Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Influence of N6-methyladenosine (m6A) modification on cell phenotype in Alzheimer's disease.", "doi": "10.1371/journal.pone.0289068", "pmid": "37549144", "authors": ["Pengyun Ni", "Kaiting Pan", "Bingbing Zhao"], "journal": "PloS one", "year": 2023, "abstract": "OBJECTIVE: Recent research has suggested that m6A modification takes on critical significance to Neurodegeneration. As indicated by the genome-wide map of m6A mRNA, genes in Alzheimer's disease model achieved significant m6A methylation. This study aimed to investigate the hub gene and pathway of m6A modification in the pathogenesis of AD. Moreover, possible brain regions with higher gene expression levels and compounds exerting potential therapeutic effects were identified. Thus, this study can provide a novel idea to explore the treatment of AD.\nMETHODS: Differential expression genes (DEGs) of GSE5281 and GSE48350 from the Gene Expression Omnibus (GEO) database were screened using the Limma package. Next, the enrichment analysis was conducted on the screened DEGs. Moreover, the functional annotation was given for N6-methyladenosine (m6A) modification gene. The protein-protein interaction network (PPI) analysis and the visualization analysis were conducted using STRING and Cytoscape. The hub gene was identified using CytoHubba. The expression levels of Hub genes in different regions of brain tissue were analyzed based on Human Protein Atlas (HPA) database and Bgee database. Subsequently, the candidate drugs targeting hub genes were screened using cMAP.\nRESULTS: A total of 42 m6A modified genes were identified in AD (20 up-regulated and 22 down-regulated genes). The above-described genes played a certain role in biological processes (e.g., retinoic acid, DNA damage response and cysteine-type endopeptidase activity), cellular components (e.g., mitochondrial protein complex), and molecular functions (e.g., RNA methyltransferase activity and ubiquitin protein ligase). KEGG results suggested that the above-mentioned genes were primarily involved in the Hippo signaling pathway of neurodegeneration disease. A total of 10 hub genes were screened using the protein-protein interaction network, and the expression of hub genes in different regions of human brain was studied. Furthermore, 10 compounds with potential therapeutic effects on AD were predicted.\nCONCLUSION: This study revealed the potential role of the m6A modification gene in Alzheimer's disease through the bioinformatics analysis. The biological changes may be correlated with retinoic acid, DNA damage response and cysteine-type endopeptidase activity, which may occur through Hippo signaling pathway. The hub genes (SOX2, KLF4, ITGB4, CD44, MSX1, YAP1, AQP1, EGR2, YWHAZ and TFAP2C) and potential drugs may provide novel research directions for future prognosis and precise treatment.", "claims": [{"id": "claim-method", "statement": "Subsequently, Limma package [25] was adopted to analyze the difference between the two groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37549144", "locator": "sections[4] \"Analysis of differentially expressed genes (DEGs)\" paragraph 2", "quote": "Subsequently, Limma package [25] was adopted to analyze the difference between the two groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Two microarray datasets (GSE5281 and GSE48350) were downloaded in this study from the Gene Expression Omnibus (GEO) database [23] (http://www.ncbi.nlm.nih.gov/gds/) investigating gene expression profiles changes in patients with Alzheimer’s disease.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37549144", "locator": "sections[3] \"Data acquisition and processing\" paragraph 2", "quote": "Two microarray datasets (GSE5281 and GSE48350) were downloaded in this study from the Gene Expression Omnibus (GEO) database [23] (http://www.ncbi.nlm.nih.gov/gds/) investigating gene expression profiles changes in patients with Alzheimer’s disease."}], "state": "complete"}, {"id": "claim-target-result", "statement": "With the Limma package for differential expression analysis, with |log2(Fold Change)| > 0.58 and P.value < 0.05 as the screening conditions, 917 differently expressed genes in brain tissues of AD patients were identified, as compared with normal brain tissues.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37549144", "locator": "sections[12] \"Identification of DEGs during AD\" paragraph 2", "quote": "With the Limma package for differential expression analysis, with |log2(Fold Change)| > 0.58 and P.value < 0.05 as the screening conditions, 917 differently expressed genes in brain tissues of AD patients were identified, as compared with normal brain tissues."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "With the Limma package for differential expression analysis, with |log2(Fold Change)| > 0.58 and P.value < 0.05 as the screening conditions, 917 differently expressed genes in brain tissues of AD patients were identified, as compared with normal brain tissues.", "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:37549144"], "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:37549144", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pone.0289068", "sha256": 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"group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Alzheimer's Disease Dataset", "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:GSE5281", "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=GSE5281", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE5281", "version": null, "note": "Two microarray datasets (GSE5281 and GSE48350) were downloaded in this study from the Gene Expression Omnibus (GEO) database [23] (http://www.ncbi.nlm.nih.gov/gds/) investigating gene expression profiles changes in patients with Alzheimer’s disease.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": 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