S-palmitoylation-related genes in Crohn's disease: Bioinformatic identification and validation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41364644", "kind": "science-record", "revision": 4, "content_hash": "sha256:d54b7aeb5e355e1a02ad8b0068242a997852c289e0d4c36dacb08640047fa598", "created_at": "2026-11-01T20:31:22Z", "updated_at": "2026-11-01T22:57:35Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "S-palmitoylation-related genes in Crohn's disease: Bioinformatic identification and validation.", "doi": "10.17305/bb.2025.13221", "pmid": "41364644", "authors": ["Yuyan Zhou", "Yuxuan Zhao"], "journal": "Biomolecules & biomedicine", "year": 2025, "abstract": "Crohn's disease (CD) is a complex chronic inflammatory bowel disorder characterized by the absence of reliable biomarkers and effective targeted treatments. Recent evidence has suggested a role for S-palmitoylation, a reversible post-translational modification, in immune regulation and intestinal inflammation. However, a systematic, gene-centric investigation explicitly linking S-palmitoylation to the pathogenesis and diagnosis of CD has not been conducted. To address this gap, our study employs a comprehensive bioinformatic analysis to identify and validate key genes associated with both CD and S-palmitoylation, assessing their potential as diagnostic biomarkers and therapeutic targets. Utilizing data from the Gene Expression Omnibus (GEO, GSE83448) and GeneCards, we identified 23 S-palmitoylation-associated differentially expressed genes (SP-DEGs) in CD. Functional enrichment analysis indicated their significant roles in cysteine-specific S-palmitoylation and immunometabolic regulation. We applied machine learning algorithms, including least absolute shrinkage and selection operator (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE), to select nine hub genes. Validation in two independent cohorts (GSE16879 and GSE59071) and ROC analysis confirmed ZDHHC23 and IFITM1 as biomarkers with high diagnostic value. These genes also exhibited correlations with immune infiltration patterns, as determined by cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT), MCPcounter, and QuanTIseq. In vitro experiments corroborated consistent changes in mRNA and protein expression for both ZDHHC23 and IFITM1, reinforcing their involvement in CD. This study offers systematic insights into the functional roles of S-palmitoylation-related genes in CD, providing a novel theoretical foundation for the development of diagnostic and targeted therapeutic strategies.", "claims": [{"id": "claim-method", "statement": "Subsequently, dual feature selection was conducted using LASSO regression and SVM-RFE algorithms.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41364644", "locator": "sections[16] \"Identification of the S-palmitoylation hub genes in CD\" paragraph 2", "quote": "Subsequently, dual feature selection was conducted using LASSO regression and SVM-RFE algorithms."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data that support the findings of this study are available in Gene Expression Omnibus (datasets with identifiers: GSE83448, GSE16879, and GSE59071), which were downloaded from http://www.ncbi.nlm.nih.gov/geo/.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41364644", "locator": "sections[24] \"Data Availability\" paragraph 2", "quote": "The data that support the findings of this study are available in Gene Expression Omnibus (datasets with identifiers: GSE83448, GSE16879, and GSE59071), which were downloaded from http://www.ncbi.nlm.nih.gov/geo/."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Differential expression analysis identified 23 S-palmitoylation-related differentially expressed genes in CD, from which machine learning identified nine consensus hub genes, including ZDHHC23 and IFITM1.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "Specifically, ZDHHC23 achieved an AUC of 0.956 (95% CI: 0.864–1.000) in the GSE16879 validation cohort."}, "evidence": [{"asset": "source:pmid:41364644", "locator": "sections[14] \"Identification of SP-DEGs in CD\" paragraph 4", "quote": "From the GeneCards database, we curated 173 S-palmitoylation-related genes, including key regulators, such as ZDHHC family acyltransferases and acyl-protein thioesterase (APT)/palmitoyl-protein thioesterase (PPT) thioesterases. Intersection analysis revealed 23 overlapping genes (Figure 2C and Table S2), designated as SP-DEGs."}, {"asset": "source:pmid:41364644", "locator": "sections[16] \"Identification of the S-palmitoylation hub genes in CD\" paragraph 2", "quote": "Venn diagram analysis revealed nine consensus candidate core genes shared by both algorithms: ZDHHC9, ZDHHC17, IFITM1, ZDHHC23, IGF2R, LAMP2, RHEB, JAM3, and ACSL5 (Figure 4E)."}, {"asset": "source:pmid:41364644", "locator": "sections[17] \"Multi-cohort validation of S-palmitoylation hub gene in CD\" paragraph 2", "quote": "Specifically, ZDHHC23 achieved an AUC of 0.956 (95% CI: 0.864–1.000) in the GSE16879 validation cohort."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Differential expression analysis identified 23 S-palmitoylation-related differentially expressed genes in CD, from which machine learning identified nine consensus hub genes, including ZDHHC23 and IFITM1.", "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:41364644"], "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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