Multi-omics analysis identified macrophages as key contributors to sex-related differences in ulcerative colitis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40636118", "kind": "science-record", "revision": 4, "content_hash": "sha256:e466b34ef613bba04b2adcb3f17cde82d79b931b5c2df433d9065ec48f9770a5", "created_at": "2026-11-01T20:30:44Z", "updated_at": "2026-11-01T22:56:48Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Multi-omics analysis identified macrophages as key contributors to sex-related differences in ulcerative colitis.", "doi": "10.3389/fimmu.2025.1569271", "pmid": "40636118", "authors": ["Xiaojie Fang", "Jiahao Yang", "Liu Yang", "Yiyou Lin", "Yanyan Li", "Xin Yin", "Xiaobing Dou", "Chenyun Miao"], "journal": "Frontiers in immunology", "year": 2025, "abstract": "Background: Ulcerative colitis (UC) has a complex etiology, and whether there are sex-related differences in its molecular mechanisms remains unclear. This study employed multi-omics analysis to explore sex-based differences in UC, aiming to provide support for personalized treatment.\nMethods: The GSE36807 and GSE206171 datasets from the GEO database were grouped by sex. Data were preprocessed using the R software, and DEGs identified using the limma package and key modules of WGCNA. LASSO regression was conducted to screen hub genes, ROC curves were used to evaluate diagnostic value, CIBERSORT was used to analyze immune cell proportions, and Spearman's correlation was performed to explore associations. The single-cell dataset GSE214695 was processed using Seurat to analyze immune cell proportion differences. Histological, immunohistochemical, and metabolomic analyses were performed on the colon tissues of DSS-induced colitis model mice.\nResults: Thirty-seven DEGs and 47 co-expression modules were identified. LASSO regression highlighted RPS4Y1 as the core gene, which was significantly upregulated in males. Females showed higher proportions of resting NK cells and M0 macrophages but a lower number of eosinophils. RPS4Y1 expression was positively correlated with resting memory CD4+ T cells and eosinophils and negatively with M0 macrophages and resting mast cells. Macrophage function exhibited sex-based disparities. Increased immune cell infiltration was observed in female colon tissues compared with that in male colon tissues. Metabolomic analysis identified 140 sex-dimorphic metabolites, with significant alterations in glutathione metabolism.\nConclusion: RPS4Y1 exhibits sex-specific expression in UC and plays a key role in immunomodulation. Mitochondrial energy metabolism contributes to sex-based macrophage differences, highlighting the importance of considering sex-specific mechanisms in UC diagnosis and individualized treatment.", "claims": [{"id": "claim-method", "statement": "Subsequently, the limma package’s moderated t-test, based on the empirical parametric Bayes method, was employed to identify DEGs between male and female samples.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40636118", "locator": "sections[4] \"Identification and analysis of differentially expressed genes\" paragraph 2", "quote": "Subsequently, the limma package’s moderated t-test, based on the empirical parametric Bayes method, was employed to identify DEGs between male and female samples."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material .", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40636118", "locator": "sections[29] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material ."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified 37 differentially expressed genes between male and female ulcerative colitis samples, including 19 downregulated and 18 upregulated in males.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40636118", "locator": "sections[16] \"Identification of DEGs between the male and female groups\" paragraph 2", "quote": "Compared to the female samples, we applied the conditions to the data and ultimately obtained 37 DEGs from the male samples. Among these, 19 genes were downregulated and 18 genes were upregulated in the male samples"}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified 37 differentially expressed genes between male and female ulcerative colitis samples, including 19 downregulated and 18 upregulated in males.", "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:40636118"], "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:GSE206171"], "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:GSE206171"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40636118", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2025.1569271", "sha256": "sha256:0e5df933b683f90f0eb51446197a7dbc2ec38d7f5f3bc43252a2b61ec4fc05e3", "bytes": 51738, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2025.1569271", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12238219", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE206171", "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=GSE206171", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE206171", "version": null, "note": "The datasets presented in this study can be found in online repositories. 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