Identification of Targets for Subsequent Treatment of Crohn's Disease Patients After Failure of Anti-TNF Therapy.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37868830", "kind": "science-record", "revision": 3, "content_hash": "sha256:4bb71561c3a8b381e9a75fb1a501b61b520f095370fb9bc2df2fd288df76e65d", "created_at": "2026-11-01T19:02:43Z", "updated_at": "2026-11-01T22:10:30Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Targets for Subsequent Treatment of Crohn's Disease Patients After Failure of Anti-TNF Therapy.", "doi": "10.2147/JIR.S422881", "pmid": "37868830", "authors": ["Yao Yao", "Liu Yang", "Zhe Zhang", "Binbin Wang", "Baisui Feng", "Zhanju Liu"], "journal": "Journal of inflammation research", "year": 2023, "abstract": "Background: Anti-TNF medications are the first-line treatment for Crohn's Disease (CD), despite the fact that a significant portion of the population continues to be ineffectively treated. This research aims to discover accurate intervention targets for the follow-up of anti-TNF non-responders using bioinformatics technology.\nMethods: GSE16879, GSE111761, and GSE52746 retrieved from the GEO database. Unbiased differentially expressed genes (DEGs) were discovered utilizing the limma and RobustRankAggreg (RRA) tools. Then, we used weighted gene co-expression network analysis (WGCNA) to identify the module most strongly associated with non responders and subjected this module to Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis with overlapping genes of the DEGs. GSEA analysis applied to check the results of GO and KEGG. Using the Cytoscape program, the protein-protein interaction (PPI) network was constructed. The software's MCODE addon and CytoHubba addon was used to find the most important modules and the hub genes. Subsequently, we employed reverse transcription-polymerase chain reaction (RT-PCR) to confirm hub gene expression from mucosal biopsy specimens.\nResults: There were a total of 142 genes co-upregulated and 65 genes co-downregulated. According to the WGCNA analysis, 42 genes were duplicated inside the light cyan module. GO and KEGG enrichment analyses of overlapped genes in nonresponders demonstrated an increase in the expression of genes associated with inflammation and immune response, consistent with GSEA results. The PPI network was constructed using 41 protein nodes and 177 edges. After validation, 8 of the top 10 genes were verified to be differentially expressed.\nConclusion: Our investigation is the first to integrate three CD databases after the anti-TNF medication treatment. We identified IL1B, CCL4, CXCL1, CXCL10, CCL3, CSF3, TREM1, and IL1RN as potential therapeutic targets for patients whose anti-TNF treatment failed.", "claims": [{"id": "claim-method", "statement": "These genes were then subjected to the RobustRankAggreg (RRA)12 algorithm to acquire the differentially expressed genes (DEGs).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37868830", "locator": "sections[4] \"Identification of Differentially Expressed Genes (DEGs)\" paragraph 2", "quote": "These genes were then subjected to the RobustRankAggreg (RRA)12 algorithm to acquire the differentially expressed genes (DEGs)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data used in this study are accessible for download on the GEO website (https://www.ncbi.nlm.nih.gov/geo). The authors affirm that the data supporting the article are available.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37868830", "locator": "sections[21] \"Data Sharing Statement\" paragraph 2", "quote": "The data used in this study are accessible for download on the GEO website (https://www.ncbi.nlm.nih.gov/geo). The authors affirm that the data supporting the article are available."}], "state": "complete"}, {"id": "claim-target-result", "statement": "RobustRankAggreg analysis identified 142 upregulated and 65 downregulated differentially expressed genes in anti-TNF nonresponders across the analyzed datasets.", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "If we set the criterion that p<0.05, 142 upregulated DEGs and 65 downregulated DEGs were discovered in nonresponders."}, "evidence": [{"asset": "source:pmid:37868830", "locator": "sections[12] \"Identification of DEGs\" paragraph 2", "quote": "If we set the criterion that p<0.05, 142 upregulated DEGs and 65 downregulated DEGs were discovered in nonresponders."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "RobustRankAggreg analysis identified 142 upregulated and 65 downregulated differentially expressed genes in anti-TNF nonresponders across the analyzed datasets.", "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:37868830"], "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:GSE111761"], "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:GSE111761"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37868830", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/JIR.S422881", "sha256": "sha256:e139c9151be1a063936c5e2ac3c7a6427489452ccfbadab3a871c48fba5e03c1", "bytes": 35847, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/JIR.S422881", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10590116", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE111761", "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=GSE111761", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE111761", "version": null, "note": "The data used in this study are accessible for download on the GEO website (https://www.ncbi.nlm.nih.gov/geo). 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