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pmid:40689242

Identification of immune and major depressive disorder-related diagnostic markers for early nonalcoholic fatty liver disease by WGCNA and machine learning.

Yuyun Jia · Yanping Cao · Qin Yin · Xueqian Li · Xiu Wen

Frontiers in bioinformatics · 2025 doi:10.3389/fbinf.2025.1594971

Paper

complete

Experiment

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Data

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Analysis

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title
Identification of immune and major depressive disorder-related diagnostic markers for early nonalcoholic fatty liver disease by WGCNA and machine learning.
doi
10.3389/fbinf.2025.1594971
pmid
40689242
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[0]
Yuyun Jia
[1]
Yanping Cao
[2]
Qin Yin
[3]
Xueqian Li
[4]
Xiu Wen
journal
Frontiers in bioinformatics
year
2025
abstract
Background: Major depressive disorder (MDD) and nonalcoholic fatty liver disease (NAFLD) are highly prevalent conditions that exhibit significant pathophysiological overlap, particularly in metabolic and immune pathways. Objective: This study aims to bridge this gap by integrating transcriptomic data from publicly available repositories and advanced machine learning algorithms to identify novel biomarkers and construct a predictive model facilitates the provision of clinical psychological nursing interventions for early-stage NAFLD in MDD patients. Method: We systematically analyzed transcriptomic data of simple steatosis (SS), nonalcoholic steatohepatitis (NASH), and major depressive disorder (MDD) from GEO databases to construct and validate a diagnostic model. After removing batch effects, we identified differentially expressed genes (DEGs) that distinguished disease and control groups. We further applied Weighted Gene Co-expression Network Analysis (WGCNA) to identify immune-related genes in SS/NASH patients versus controls. The intersection of shared DEGs across both conditions and WGCNA-identified genes was determined and subjected to functional enrichment analysis. Immune cell infiltration levels were quantified using single-sample gene set enrichment analysis (ssGSEA). A predictive model for SS/NASH was developed by evaluating nine machine-learning algorithms with 10-fold cross-validation on the datasets. Results: Fourteen genes strongly linked to both the immune system and the two conditions were identified. Immune cell infiltration profiling revealed distinct immune landscapes in patients versus healthy controls. Moreover, an eight-gene signature was developed, demonstrating superior diagnostic accuracy in both testing and training cohorts. Notably, these eight genes were found to correlate with the severity of early-stage NAFLD. Conclusion: This study established a predictive model for early-stage NAFLD through the integration of bioinformatics and machine learning approaches, with a focus on immune- and MDD-related genes. The eight-gene signature identified in this study represents a novel diagnostic tool for precision medicine, enabling targeted psychological nursing intervention in comorbid populations.
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sections[4] "Identification of differentially expressed genes (DEGs)" paragraph 2
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Differentially expressed genes (DEGs) were identified using the limma (3.60.6) package in R (version 4.4.2), a tool specialized for RNA-seq data analysis.
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The study developed an eight-gene signature for diagnosing MDD-related early-stage NAFLD using integrated transcriptomic data and machine learning.
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Moreover, an eight-gene signature was developed, demonstrating superior diagnostic accuracy in both testing and training cohorts.
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sample_count
192
group_sizes
null
group_sizes_basis
null
platform
570
taxon
Homo sapiens
title
Gene expression analysis in whole blood samples obtained from donors diagnosed with MDD compared to healthy controls
resolution_checked_at
2026-11-01T15:39:55Z
resolution_check
identifier_resolution_only_no_download_no_licence_read
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[5]
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[7]
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[9]
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[11]
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partial
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id
method-1
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differential_expression
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limma_voom
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dsl_operations array · 3 items
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normalise_counts
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differential_expression_fit
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evidence object · 3 fields
score
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quote
Differentially expressed genes (DEGs) were identified using the limma (3.60.6) package in R (version 4.4.2), a tool specialized for RNA-seq data analysis.
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specific
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evidence object · 3 fields
score
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quote
analysis of variance
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id
method-3
family
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specific
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label
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dsl_operations array · 1 item
[0]
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missing_operations array · 0 items
parameters object · 0 fields
data_shapes array · 1 item
[0]
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evidence object · 3 fields
score
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band
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quote
pathway enrichment
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gaps array · 1 item
[0]
method.reader_differs_from_extractor
capability object · 3 fields
state
complete
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[0] object · 6 fields
capability_id
capability:computational_analysis
label
Computational analysis platform
assay_families array · 9 items
[0]
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candidate
Automated Assays Laravel application and simulated adapters
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readiness object · 8 fields
state
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tier
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required_operations array · 3 items
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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
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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 · 6 items
[0]
GSE76826
[1]
GSE98793
[2]
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[3]
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[5]
GSE89632
resolved_accessions array · 6 items
[0]
GSE76826
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GSE98793
[2]
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[3]
GSE63067
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[5]
GSE89632
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 GSE76826, GSE98793, GSE48452, GSE63067, GSE126848, GSE89632 in NCBI Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read.
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dsl_operations array · 3 items
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differential_expression_fit
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assets array · 2 items
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source:pmid:40689242
[1]
data:geo:GSE126848
steps array · 1 item
[0]
run_analysis
must_build object · 5 fields
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data_gaps array · 1 item
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data:geo:GSE126848
gaps array · 0 items
review object · 5 fields
state
partial
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kind
extraction_review
reader object · 5 fields
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MiniMax-M3.1-Flash
provider
minimax
provider_family
minimax
read_at
2026-11-01T19:57:33Z
independence
single_reader
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method
verbatim
availability
verbatim
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prompt_tokens
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stages array · 1 item
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id
extraction
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pmid:40689242
type
paper
label
pmid:40689242
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source:pmid:40689242
type
manuscript
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PMID 40689242 full text
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data:geo:GSE126848
type
dataset
label
GEO GSE126848
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activity-reading-sci-2026-11-01
type
classification
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id
pmid:40689242
type
paper
label
pmid:40689242
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id
source:pmid:40689242
type
manuscript
label
PMID 40689242 full text
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id
data:geo:GSE126848
type
dataset
label
GEO GSE126848
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agent:corpus-assay-engine
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id
activity-read-40689242
type
extraction
used array · 1 item
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agent:minimax-reader
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activity-resolve-GSE126848
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used array · 1 item
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Corpus assay engine
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pmid:40689242
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sha256:63003244cec2f22e7f71e85541bd8497af5f497b3984d3a500e7cad69df2f5c6
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[3]
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[5]
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[6]
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[7]
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[9]
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[11]
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evidence array · 2 items
[0]
study aims to bridge this gap by integrating transcriptomic data from publicly available repositories an
[1]
patients. Method: We systematically analyzed transcriptomic data of simple steatosis (SS), nonalcoholic
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paper_text_order:393
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assay:1
[1] object · 11 fields
role
analysis
definition_id
differential_expression
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Differentially expressed genes (DEGs) were identified using the limma (3.60.6) package in R (version 4.4.2), a tool specialized for RNA-seq data analysis.
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40689242", "kind": "science-record", "revision": 4, "content_hash": "sha256:c4fc940f0f5aca8719182edc813671ff343da608353c6b632d7f6c18ab916bdc", "created_at": "2026-11-01T20:30:47Z", "updated_at": "2026-11-01T22:56:52Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of immune and major depressive disorder-related diagnostic markers for early nonalcoholic fatty liver disease by WGCNA and machine learning.", "doi": "10.3389/fbinf.2025.1594971", "pmid": "40689242", "authors": ["Yuyun Jia", "Yanping Cao", "Qin Yin", "Xueqian Li", "Xiu Wen"], "journal": "Frontiers in bioinformatics", "year": 2025, "abstract": "Background: Major depressive disorder (MDD) and nonalcoholic fatty liver disease (NAFLD) are highly prevalent conditions that exhibit significant pathophysiological overlap, particularly in metabolic and immune pathways.\nObjective: This study aims to bridge this gap by integrating transcriptomic data from publicly available repositories and advanced machine learning algorithms to identify novel biomarkers and construct a predictive model facilitates the provision of clinical psychological nursing interventions for early-stage NAFLD in MDD patients.\nMethod: We systematically analyzed transcriptomic data of simple steatosis (SS), nonalcoholic steatohepatitis (NASH), and major depressive disorder (MDD) from GEO databases to construct and validate a diagnostic model. After removing batch effects, we identified differentially expressed genes (DEGs) that distinguished disease and control groups. We further applied Weighted Gene Co-expression Network Analysis (WGCNA) to identify immune-related genes in SS/NASH patients versus controls. The intersection of shared DEGs across both conditions and WGCNA-identified genes was determined and subjected to functional enrichment analysis. Immune cell infiltration levels were quantified using single-sample gene set enrichment analysis (ssGSEA). A predictive model for SS/NASH was developed by evaluating nine machine-learning algorithms with 10-fold cross-validation on the datasets.\nResults: Fourteen genes strongly linked to both the immune system and the two conditions were identified. Immune cell infiltration profiling revealed distinct immune landscapes in patients versus healthy controls. Moreover, an eight-gene signature was developed, demonstrating superior diagnostic accuracy in both testing and training cohorts. Notably, these eight genes were found to correlate with the severity of early-stage NAFLD.\nConclusion: This study established a predictive model for early-stage NAFLD through the integration of bioinformatics and machine learning approaches, with a focus on immune- and MDD-related genes. The eight-gene signature identified in this study represents a novel diagnostic tool for precision medicine, enabling targeted psychological nursing intervention in comorbid populations.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes (DEGs) were identified using the limma (3.60.6) package in R (version 4.4.2), a tool specialized for RNA-seq data analysis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40689242", "locator": "sections[4] \"Identification of differentially expressed genes (DEGs)\" paragraph 2", "quote": "Differentially expressed genes (DEGs) were identified using the limma (3.60.6) package in R (version 4.4.2), a tool specialized for RNA-seq data analysis."}], "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:40689242", "locator": "sections[22] \"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 study developed an eight-gene signature for diagnosing MDD-related early-stage NAFLD using integrated transcriptomic data and machine learning.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40689242", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Moreover, an eight-gene signature was developed, demonstrating superior diagnostic accuracy in both testing and training cohorts."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study developed an eight-gene signature for diagnosing MDD-related early-stage NAFLD using integrated transcriptomic data and machine learning.", "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:40689242"], "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:GSE126848"], "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:GSE126848"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40689242", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fbinf.2025.1594971", "sha256": 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