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pmid:40799218
Commonalities and differences in gene expression patterns in major depressive disorder and chronic spontaneous urticaria: implications for comorbidity.
Yibo Jiang · Wen Li · Lihao Zheng · Nan Ba
Frontiers in genetics · 2025 doi:10.3389/fgene.2025.1560832
Paper
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Experiment
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Data
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Complete file
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Clinical evidence has shown significant comorbidity between CSU and major depressive disorder (MDD), but our understanding of the underlying molecular mechanisms and how they differ by sex remains limited. In this work, five gene expression datasets were obtained from the Gene Expression Omnibus (GEO), encompassing three for MDD (GSE52790, GSE38206, GSE76826) and two exclusively whole-blood datasets for CSU (GSE167882, GSE72541). Following data preprocessing and batch effect correction, differentially expressed genes (DEGs) in CSU and MDD were identified in male, female, and total populations. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were used to characterize putative pathophysiological mechanisms. Subsequently, machine learning algorithms were implemented via 10-fold cross-validation to build transcriptomic classifiers for MDD in a sex-stratified manner. Results indicated shared molecular patterns between CSU and MDD, with 26 key genes in the total population, 6 in males and 7 in females. Further feature selection yielded 6 core transcriptomic features in the total population (BCL11A, BEX2, C5AR1, DDX60L, LCE3D, NAMPT), 2 in males (GNAQ, RNF19B), and 4 in females (GNG7, LCE3D, PYGL, UPP1). Validation analyses showed that these transcriptomic classifiers conferred high classification accuracy, with the model for females surpassing that for males. Potential drug candidates targeting shared molecular mechanisms were identified. Overall, these findings reveal sex-specific molecular signatures that may underlie CSU-MDD comorbidity and offer insight into future precision treatment paradigms.", "claims": [{"id": "claim-method", "statement": "The “limma” package was used, applying a threshold of |log2FC|>0.25 and p<0.05 Illumina (2015).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40799218", "locator": "sections[5] \"2.3 Identification of differentially expressed genes (DEGs)\" paragraph 2", "quote": "The “limma” package was used, applying a threshold of |log2FC|>0.25 and p<0.05 Illumina (2015)."}], "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 author.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40799218", "locator": "sections[24] \"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 author."}], "state": "complete"}, {"id": "claim-target-result", "statement": "An initial screening of the CSU data sets identified 690 differentially expressed genes (DEGs) according to the criteria of |log2FC|>0.25 and FDR <0.05.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40799218", "locator": "sections[13] \"3.2 Results of differentially expressed gene analysis\" paragraph 2", "quote": "An initial screening of the CSU data sets identified 690 differentially expressed genes (DEGs) according to the criteria of |log2FC|>0.25 and FDR <0.05"}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "An initial screening of the CSU data sets identified 690 differentially expressed genes (DEGs) according to the criteria of |log2FC|>0.25 and FDR <0.05.", "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:40799218"], "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. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE52790", "GSE38206", "GSE76826", "GSE167882", "GSE72541"], "resolved_accessions": ["GSE52790", "GSE38206", "GSE76826", "GSE167882", "GSE72541"], "statements": ["The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author."], "basis": "The paper names GSE52790, GSE38206, GSE76826, GSE167882, GSE72541 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:40799218", "data:geo:GSE167882"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE167882"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:59:08Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 12246, "completion_tokens": 1554, "cached_tokens": 256}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:40799218", "type": "paper", "label": "pmid:40799218"}, {"id": "source:pmid:40799218", "type": "manuscript", "label": "PMID 40799218 full text"}, {"id": "data:geo:GSE167882", "type": "dataset", "label": "GEO GSE167882"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40799218", "type": "paper", "label": "pmid:40799218"}, {"id": "source:pmid:40799218", "type": "manuscript", "label": "PMID 40799218 full text"}, {"id": "data:geo:GSE167882", "type": "dataset", "label": "GEO GSE167882"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40799218", "type": "extraction", "used": ["source:pmid:40799218"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE167882", "type": "accession_resolution", "used": ["data:geo:GSE167882"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"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": {"parent_id": "pmid:40799218", "parent_hash": "sha256:dcabc6a8d50716d08bf25f1fb97f1ac024b1e07067d7070cf9c7268b38bc354d", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE167882 licence not read", "asset:data:geo:GSE167882 not downloaded", "asset:data:geo:GSE38206 licence not read", "asset:data:geo:GSE38206 not downloaded", "asset:data:geo:GSE52790 licence not read", "asset:data:geo:GSE52790 not downloaded", "asset:data:geo:GSE72541 licence not read", "asset:data:geo:GSE72541 not downloaded", "asset:data:geo:GSE76826 licence not read", "asset:data:geo:GSE76826 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["The “limma” package was used, applying a threshold of |log2FC|>0.25 and p<0.05 Illumina (2015)."], "order_basis": "analysis_only", "id": "assay:1"}]}