Identification of ubiquitination-related key biomarkers and immune infiltration in Crohn's disease by bioinformatics analysis and machine learning.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:39870856", "kind": "science-record", "revision": 4, "content_hash": "sha256:f929c5ad900362dc5653b67739d62eb8850b965b92de5fbc90ec64351e6dac95", "created_at": "2026-11-01T20:30:09Z", "updated_at": "2026-11-01T22:56:03Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of ubiquitination-related key biomarkers and immune infiltration in Crohn's disease by bioinformatics analysis and machine learning.", "doi": "10.1038/s41598-025-88148-4", "pmid": "39870856", "authors": ["Wei Chen", "Zeyan Xu", "Haitao Sun", "Wen Feng", "Zhenhua Huang"], "journal": "Scientific reports", "year": 2025, "abstract": "Crohn's disease (CD) is a chronic inflammatory bowel disease with an unknown etiology. Ubiquitination plays a significant role in the pathogenesis of CD. This study aimed to explore the functional roles of ubiquitination-related genes in CD. Differentially expressed ubiquitination-related genes were identified by intersecting differentially expressed genes (DEGs) from the GSE95095 dataset in the Gene Expression Omnibus (GEO) database with a set of ubiquitination-related genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Key genes were selected by combining hub genes from the protein-protein interaction (PPI) network with feature genes identified by Lasso and Random Forest (RF) algorithms. Additionally, the correlation between key genes and immune infiltration was assessed, and Gene Set Enrichment Analysis (GSEA) of key genes was conducted. The efficacy of key genes was validated using ROC curves in an external dataset, and their expression was confirmed in LPS-induced Caco-2 cells through RT-qPCR. A total of 32 ubiquitination-related DEGs were identified, and two key genes (UBE2R2, NEDD4L) were selected. The infiltration of M2 macrophages was reduced in CD patients, with UBE2R2 expression negatively correlated and NEDD4L expression positively correlated with M2 macrophage infiltration. GSEA indicated that UBE2R2 was enriched in terpenoid backbone biosynthesis, regulation of autophagy, and limonene and pinene degradation, while NEDD4L was enriched in lysosome, Wnt signaling, and calcium signaling pathways. ROC curves demonstrated superior efficacy for NEDD4L. In LPS-induced Caco-2 cells, UBE2R2 expression increased, while NEDD4L expression decreased. A comprehensive analysis of the functional relationship between ubiquitination-related genes and CD can enhance understanding of CD pathogenesis and suggest potential therapeutic targets.", "claims": [{"id": "claim-method", "statement": "In order to identify DEGs between CD and normal controls base on the GSE95095 dataset, the limma package in the R software was utilized.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39870856", "locator": "sections[15] \"Identification of ubiquitination-related DEGs\" paragraph 2", "quote": "In order to identify DEGs between CD and normal controls base on the GSE95095 dataset, the limma package in the R software was utilized."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analysed during the current study are available in the Gene Expression Omnibus repository (https://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39870856", "locator": "sections[27] \"Data availability\" paragraph 2", "quote": "The datasets analysed during the current study are available in the Gene Expression Omnibus repository (https://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 32 ubiquitination-related DEGs were identified, and two key genes (UBE2R2, NEDD4L) were selected.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39870856", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "A total of 32 ubiquitination-related DEGs were identified, and two key genes (UBE2R2, NEDD4L) were selected."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 32 ubiquitination-related DEGs were identified, and two key genes (UBE2R2, NEDD4L) were selected.", "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:39870856"], "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:GSE83448"], "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:GSE83448"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39870856", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1038/s41598-025-88148-4", "sha256": "sha256:e3ad3099923bc145d3341251279719123dcc9f45dd0ba8cb6a8251b06cf03a0c", "bytes": 37220, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1038/s41598-025-88148-4", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11772853", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE83448", "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=GSE83448", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE83448", "version": null, "note": "The datasets analysed during the current study are available in the Gene Expression Omnibus repository (https://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analysed during the current study are available in the Gene Expression Omnibus repository (https://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2203115", "GSM2203116", "GSM2203117", "GSM2203118", "GSM2203119", "GSM2203120", "GSM2203121", "GSM2203122", "GSM2203123", "GSM2203124", "GSM2203125", "GSM2203126", "GSM2203127", "GSM2203128", "GSM2203129", "GSM2203130", "GSM2203131", "GSM2203132", "GSM2203133", "GSM2203134", "GSM2203135", "GSM2203136", "GSM2203137", "GSM2203138", "GSM2203139", "GSM2203140", "GSM2203141", "GSM2203142", "GSM2203143", "GSM2203144", "GSM2203145", "GSM2203146", "GSM2203147", "GSM2203148", "GSM2203149", "GSM2203150", "GSM2203151", "GSM2203152", "GSM2203153", "GSM2203154", "GSM2203155", "GSM2203156", "GSM2203157", "GSM2203158", "GSM2203159", "GSM2203160", "GSM2203161", "GSM2203162", "GSM2203163", "GSM2203164", "GSM2203165", "GSM2203166", "GSM2203167"], "sample_count": 53, "group_sizes": null, "group_sizes_basis": null, "platform": "18134", "taxon": "Homo sapiens", "title": "Genome-wide transcriptional analysis in intestinal biopsies from Crohn's disease (CD) patients.", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE95095", "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=GSE95095", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE95095", "version": null, "note": "The datasets analysed during the current study are available in the Gene Expression Omnibus repository (https://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analysed during the current study are available in the Gene Expression Omnibus repository (https://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2496058", "GSM2496059", "GSM2496060", "GSM2496061", "GSM2496062", "GSM2496063", "GSM2496064", "GSM2496065", "GSM2496066", "GSM2496067", "GSM2496068", "GSM2496069", "GSM2496070", "GSM2496071", "GSM2496072", "GSM2496073", "GSM2496074", "GSM2496075", "GSM2496076", "GSM2496077", "GSM2496078", "GSM2496079", "GSM2496080", "GSM2496081", "GSM2496082", "GSM2496083", "GSM2496084", "GSM2496085", "GSM2496086", "GSM2496087", "GSM2496088", "GSM2496089", "GSM2496090", "GSM2496091", "GSM2496092", "GSM2496093", "GSM2496094", "GSM2496095", "GSM2496096", "GSM2496097", "GSM2496098", "GSM2496099", "GSM2496100", "GSM2496101", "GSM2496102", "GSM2496103", "GSM2496104", "GSM2496105", "GSM2496106", "GSM2496107", "GSM2496108", "GSM2496109", "GSM2496110", "GSM2496111", "GSM2496112", "GSM2496113", "GSM2496114", "GSM2496115", "GSM2496116", "GSM2496117"], "sample_count": 60, "group_sizes": null, "group_sizes_basis": null, "platform": "14951", "taxon": "Homo sapiens", "title": "Differential Gene Expression between involved and uninvolved sites of Crohn’s disease: Insights into a Distinctive Pathogenesis Profile", "resolution_checked_at": "2026-11-01T18:06:44Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE83448 not downloaded", "asset:data:geo:GSE83448 licence not read", "asset:data:geo:GSE95095 not downloaded", "asset:data:geo:GSE95095 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "In order to identify DEGs between CD and normal controls base on the GSE95095 dataset, the limma package in the R software was utilized."}}, {"id": "method-2", "family": "group_comparison", "specific": "mann_whitney", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_mann_whitney"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Mann-Whitney"}}, {"id": "method-3", "family": "machine_learning", "specific": "random_forest", "label": "Machine learning", "dsl_operations": [], "missing_operations": ["machine_learning_random_forest"], "expressible": false, "parameters": {}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 0.7, "band": "medium", "quote": "Random Forest"}}, {"id": "method-4", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"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": {"tier": "R1", "reachable": true, "accessions": ["GSE95095", "GSE83448"], "resolved_accessions": ["GSE95095", "GSE83448"], "statements": ["The datasets analysed during the current study are available in the Gene Expression Omnibus repository (https://www.ncbi.nlm.nih.gov/geo/)."], "basis": "The paper names GSE95095, GSE83448 in Gene Expression Omnibus 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:39870856", "data:geo:GSE83448"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE83448"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:45:16Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 10843, "completion_tokens": 1270, "cached_tokens": 128}}, "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:39870856", "type": "paper", "label": "pmid:39870856"}, {"id": "source:pmid:39870856", "type": "manuscript", "label": "PMID 39870856 full text"}, {"id": "data:geo:GSE83448", "type": "dataset", "label": "GEO GSE83448"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:39870856", "type": "paper", "label": "pmid:39870856"}, {"id": "source:pmid:39870856", "type": "manuscript", "label": "PMID 39870856 full text"}, {"id": "data:geo:GSE83448", "type": "dataset", "label": "GEO GSE83448"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-39870856", "type": "extraction", "used": ["source:pmid:39870856"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE83448", "type": "accession_resolution", "used": ["data:geo:GSE83448"], "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:39870856", "parent_hash": "sha256:70a8f7b3060912f6553b86180430a47598a88ddd2ea6e63ab3869a5ba3a11fce", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE83448 licence not read", "asset:data:geo:GSE83448 not downloaded", "asset:data:geo:GSE95095 licence not read", "asset:data:geo:GSE95095 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["onfirmed in LPS-induced Caco-2 cells through RT-qPCR. A total of 32 ubiquitination-related DEGs w", "irmed in LPS-induced Caco-2 cells through RT-qPCR. A total of 32 ubiquitination-related DEGs w"], "order_basis": "paper_text_order:1158", "id": "assay:1"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["and Cell Biology (Shanghai, China), and was cultured in DMEM medium containing 10%FBS, 100 U/mL peni"], "order_basis": "paper_text_order:2169", "id": "assay:2"}, {"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": ["In order to identify DEGs between CD and normal controls base on the GSE95095 dataset, the limma package in the R software was utilized."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}