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pmid:40070840

Identification of lipid metabolism related immune markers in atherosclerosis through machine learning and experimental analysis.

Hang Chen · Biao Wu · Kunyu Guan · Liang Chen · Kangjie Chai · Maoji Ying · Dazhi Li · Weicheng Zhao

Frontiers in immunology · 2025 doi:10.3389/fimmu.2025.1549150

Paper

complete

Experiment

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Data

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Analysis

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Execution

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pmid:40070840
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title
Identification of lipid metabolism related immune markers in atherosclerosis through machine learning and experimental analysis.
doi
10.3389/fimmu.2025.1549150
pmid
40070840
authors array · 8 items
[0]
Hang Chen
[1]
Biao Wu
[2]
Kunyu Guan
[3]
Liang Chen
[4]
Kangjie Chai
[5]
Maoji Ying
[6]
Dazhi Li
[7]
Weicheng Zhao
journal
Frontiers in immunology
year
2025
abstract
Background: Atherosclerosis is a significant contributor to cardiovascular disease, and conventional diagnostic methods frequently fall short in the timely and accurate detection of early-stage atherosclerosis. Abnormal lipid metabolism plays a critical role in the development of atherosclerosis. Consequently, the identification of new diagnostic markers is essential for the precise diagnosis of this condition. Method: The datasets related to atherosclerosis utilized in this research were obtained from the GEO database (GSE2470, GSE24495, GSE100927 and GSE43292). The ssGSEA technique was first utilized to assess lipid metabolism scores in samples affected by atherosclerosis, thereby aiding in the discovery of important regulatory genes linked to lipid metabolism via WGCNA. Following this, differential expression analysis and functional evaluations were carried out, after which various machine learning approaches were employed to determine significant diagnostic genes for atherosclerosis. A diagnostic model was then developed and validated through several machine learning algorithms. Furthermore, molecular docking studies were conducted to analyze the binding affinity of these key markers with therapeutic agents for atherosclerosis. The ssGSEA technique was also used to measure immune cell scores in atherosclerotic samples, aiding the exploration of the connection between key diagnostic markers and immune cells. Finally, the expression variations of the identified pivotal genes were confirmed through experimental validation. Result: WGCNA identified 302 lipid metabolism-related genes in atherosclerotic samples, and functional analysis revealed that these genes are associated with multiple immune pathways. Through further differential analysis and screening using machine learning algorithms, APLNR, PCDH12, PODXL, SLC40A1, TM4SF18, and TNFRSF25 were identified as key diagnostic genes for atherosclerosis. The diagnostic model we constructed was confirmed to predict the occurrence of atherosclerosis with high accuracy, and molecular docking studies indicated that these six key diagnostic genes have potential as drug targets. Additionally, the ssGSEA algorithm further validated the association of these diagnostic genes with various immune cells. Finally, the expression levels of these six genes were experimentally confirmed. Conclusion: Our study introduces novel lipid metabolism-related diagnostic markers for atherosclerosis and emphasizes their potential as immune-related drug targets. This research provides a valuable approach for the predictive diagnosis and targeted therapy of atherosclerosis.
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Out of various algorithm combinations, XGBoost proved to be the most effective for constructing the model.
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The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.
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sections[15] "Integration of machine learning algorithms for diagnostic model development" paragraph 2
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The area under the curve (AUC) for the training data from GSE100927 was recorded at 0.982, while the AUC for the validation dataset GSE43292 stood at 0.836.
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[221]
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[223]
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[225]
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GSM607330
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[231]
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[232]
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[233]
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[234]
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[235]
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[236]
GSM607340
[237]
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[239]
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[240]
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[241]
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[242]
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[243]
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[283]
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[284]
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[285]
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[286]
GSM607390
[287]
GSM607391
[288]
GSM607392
[289]
GSM607393
sample_count
290
group_sizes
null
group_sizes_basis
null
platform
10687
taxon
Homo sapiens
title
Gene expression profiling of human atherosclerotic plaque: 290 peripheral plaques
resolution_checked_at
2026-11-01T20:16:08Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
[4] object · 15 fields
id
data:geo:GSE43292
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=GSE43292
sha256
null
bytes
null
access
open
state
resolved
reader
null
reader_status
reader_required
identifier
GSE43292
version
null
note
The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.
structure object · 15 fields
repository
GEO
access_route
GEO accession URL
access_statement_verbatim
The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.
access_statement_kind
data_availability_statement
sample_accessions array · 64 items
[0]
GSM1060117
[1]
GSM1060118
[2]
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[4]
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[5]
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[6]
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[7]
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[8]
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[10]
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GSM1060180
sample_count
64
group_sizes
null
group_sizes_basis
null
platform
6244
taxon
Homo sapiens
title
Genome-wide expression study of human carotid atheroma
resolution_checked_at
2026-11-01T15:39:54Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
downloaded
false
licence_read
false
gaps array · 8 items
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asset:data:geo:GSE100927 not downloaded
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asset:data:geo:GSE100927 licence not read
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[3]
asset:data:geo:GSE24495 licence not read
[4]
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[5]
asset:data:geo:GSE24702 licence not read
[6]
asset:data:geo:GSE43292 not downloaded
[7]
asset:data:geo:GSE43292 licence not read
analysis object · 4 fields
state
complete
methods array · 2 items
[0] object · 10 fields
id
method-1
family
machine_learning
specific
gradient_boosting
label
Machine learning
dsl_operations array · 3 items
[0]
train_classifier
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cross_validate
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roc_auc
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
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labelled_feature_matrix
evidence object · 3 fields
score
1
band
verbatim
quote
Out of various algorithm combinations, XGBoost proved to be the most effective for constructing the model.
[1] object · 10 fields
id
method-2
family
diagnostic_evaluation
specific
roc
label
Diagnostic test evaluation
dsl_operations array · 6 items
[0]
confusion_counts
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roc_curve
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sensitivity_specificity
[3]
solve_confusion_matrix
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classification_metrics
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published_precision_envelope
missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
reference_standard_and_test
evidence object · 3 fields
score
0.8
band
high
quote
ROC curve
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
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survival_analysis
[3]
statistical_regression
[4]
pca
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molecular_docking
[6]
network_analysis
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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
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train_classifier
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cross_validate
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roc_auc
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: gradient_boosting.
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 · 4 items
[0]
GSE24702
[1]
GSE24495
[2]
GSE100927
[3]
GSE43292
resolved_accessions array · 4 items
[0]
GSE24702
[1]
GSE24495
[2]
GSE100927
[3]
GSE43292
statements array · 1 item
[0]
The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.
basis
The paper names GSE24702, GSE24495, GSE100927, GSE43292 in 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
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train_classifier
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cross_validate
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roc_auc
assets array · 2 items
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source:pmid:40070840
[1]
data:geo:GSE100927
steps array · 1 item
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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:GSE100927
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
2026-11-01T19:48:11Z
independence
single_reader
evidence_check object · 2 fields
method
verbatim
availability
verbatim
calls
5
usage object · 3 fields
prompt_tokens
10096
completion_tokens
1994
cached_tokens
128
stages array · 1 item
[0] object · 4 fields
id
extraction
state
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
runs array · 0 items
gaps array · 1 item
[0]
execution.not_run
provenance object · 7 fields
entities array · 3 items
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id
pmid:40070840
type
paper
label
pmid:40070840
[1] object · 3 fields
id
source:pmid:40070840
type
manuscript
label
PMID 40070840 full text
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id
data:geo:GSE100927
type
dataset
label
GEO GSE100927
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:40070840
type
paper
label
pmid:40070840
[1] object · 3 fields
id
source:pmid:40070840
type
manuscript
label
PMID 40070840 full text
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id
data:geo:GSE100927
type
dataset
label
GEO GSE100927
agent
agent:corpus-assay-engine
[1] object · 4 fields
id
activity-read-40070840
type
extraction
used array · 1 item
[0]
source:pmid:40070840
agent
agent:minimax-reader
[2] object · 4 fields
id
activity-resolve-GSE100927
type
accession_resolution
used array · 1 item
[0]
data:geo:GSE100927
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
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lineage object · 4 fields
parent_id
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parent_hash
sha256:f97401dd9e58eba7f233b4ec571e52ef9db743949fac6e817c0b35df6109de74
fork_of
null
gaps array · 12 items
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[6]
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assays array · 1 item
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role
analysis
definition_id
machine_learning
definition_version
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roc_auc
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supported
source_hashes object · 1 field
dsl_catalogue
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evidence array · 1 item
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Out of various algorithm combinations, XGBoost proved to be the most effective for constructing the model.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40070840", "kind": "science-record", "revision": 4, "content_hash": "sha256:d611f6a76454690c1b01664ecd68db4f411a2bb2b0e6c9cc4502f2ebdfa575b4", "created_at": "2026-11-01T20:30:17Z", "updated_at": "2026-11-01T22:56:13Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of lipid metabolism related immune markers in atherosclerosis through machine learning and experimental analysis.", "doi": "10.3389/fimmu.2025.1549150", "pmid": "40070840", "authors": ["Hang Chen", "Biao Wu", "Kunyu Guan", "Liang Chen", "Kangjie Chai", "Maoji Ying", "Dazhi Li", "Weicheng Zhao"], "journal": "Frontiers in immunology", "year": 2025, "abstract": "Background: Atherosclerosis is a significant contributor to cardiovascular disease, and conventional diagnostic methods frequently fall short in the timely and accurate detection of early-stage atherosclerosis. Abnormal lipid metabolism plays a critical role in the development of atherosclerosis. Consequently, the identification of new diagnostic markers is essential for the precise diagnosis of this condition.\nMethod: The datasets related to atherosclerosis utilized in this research were obtained from the GEO database (GSE2470, GSE24495, GSE100927 and GSE43292). The ssGSEA technique was first utilized to assess lipid metabolism scores in samples affected by atherosclerosis, thereby aiding in the discovery of important regulatory genes linked to lipid metabolism via WGCNA. Following this, differential expression analysis and functional evaluations were carried out, after which various machine learning approaches were employed to determine significant diagnostic genes for atherosclerosis. A diagnostic model was then developed and validated through several machine learning algorithms. Furthermore, molecular docking studies were conducted to analyze the binding affinity of these key markers with therapeutic agents for atherosclerosis. The ssGSEA technique was also used to measure immune cell scores in atherosclerotic samples, aiding the exploration of the connection between key diagnostic markers and immune cells. Finally, the expression variations of the identified pivotal genes were confirmed through experimental validation.\nResult: WGCNA identified 302 lipid metabolism-related genes in atherosclerotic samples, and functional analysis revealed that these genes are associated with multiple immune pathways. Through further differential analysis and screening using machine learning algorithms, APLNR, PCDH12, PODXL, SLC40A1, TM4SF18, and TNFRSF25 were identified as key diagnostic genes for atherosclerosis. The diagnostic model we constructed was confirmed to predict the occurrence of atherosclerosis with high accuracy, and molecular docking studies indicated that these six key diagnostic genes have potential as drug targets. Additionally, the ssGSEA algorithm further validated the association of these diagnostic genes with various immune cells. Finally, the expression levels of these six genes were experimentally confirmed.\nConclusion: Our study introduces novel lipid metabolism-related diagnostic markers for atherosclerosis and emphasizes their potential as immune-related drug targets. This research provides a valuable approach for the predictive diagnosis and targeted therapy of atherosclerosis.", "claims": [{"id": "claim-method", "statement": "Out of various algorithm combinations, XGBoost proved to be the most effective for constructing the model.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40070840", "locator": "sections[15] \"Integration of machine learning algorithms for diagnostic model development\" paragraph 2", "quote": "Out of various algorithm combinations, XGBoost proved to be the most effective for constructing the model."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40070840", "locator": "sections[23] \"Data availability statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The area under the curve (AUC) for the training data from GSE100927 was recorded at 0.982, while the AUC for the validation dataset GSE43292 stood at 0.836.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40070840", "locator": "sections[15] \"Integration of machine learning algorithms for diagnostic model development\" paragraph 2", "quote": "The area under the curve (AUC) for the training data from GSE100927 was recorded at 0.982, while the AUC for the validation dataset GSE43292 stood at 0.836."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The area under the curve (AUC) for the training data from GSE100927 was recorded at 0.982, while the AUC for the validation dataset GSE43292 stood at 0.836.", "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:40070840"], "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:GSE100927"], "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:GSE100927"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40070840", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2025.1549150", "sha256": "sha256:b7f8875436d28c2e0d859a21a9a0a47668c621da80a2fec0db8714f319b1814e", "bytes": 40378, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2025.1549150", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11893410", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE100927", "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=GSE100927", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE100927", "version": null, "note": "The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/supplementary material. 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