Neutrophil Infiltration Characterized by Upregulation of S100A8, S100A9, S100A12 and CXCR2 Is Associated With the Co-Occurrence of Crohn's Disease and Peripheral Artery Disease.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35795659", "kind": "science-record", "revision": 5, "content_hash": "sha256:ea0909a58751a30b7978efe0081d12192bc24c84542d42ced4c80a21b722a873", "created_at": "2026-11-01T18:14:50Z", "updated_at": "2026-11-01T22:49:29Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Neutrophil Infiltration Characterized by Upregulation of S100A8, S100A9, S100A12 and CXCR2 Is Associated With the Co-Occurrence of Crohn's Disease and Peripheral Artery Disease.", "doi": "10.3389/fimmu.2022.896645", "pmid": "35795659", "authors": ["Ziping Yao", "Bihui Zhang", "Guochen Niu", "Ziguang Yan", "Xiaoqiang Tong", "Yinghua Zou", "Yuan Li", "Min Yang"], "journal": "Frontiers in immunology", "year": 2022, "abstract": "Background: Crohn's disease (CD) and peripheral arterial disease (PAD) are closely related. The pathophysiological mechanisms underlying the coexistence of CD and PAD are unknown. The aim of this study was to investigate the key molecules and pathways mediating the co-occurrence of CD and PAD through quantitative bioinformatic analysis of a public RNA sequencing database.\nMethods: Datasets of CD (GSE111889) and PAD (GSE120642) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed using the 'edgeR' and 'limma' packages of R. Gene Ontology and Kyoto Encyclopedia analyses of common DEGs were performed to explore the functions of DEGs. Protein-protein interaction (PPI) networks were established by the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized by Cytoscape. Hub genes were selected using the plugin cytoHubba. Hub gene validation was performed in GSE95095 for CD and GSE134431 for PAD. Receiver operating characteristic curves were used to evaluate the predictive values of the hub genes. Gene set enrichment analysis and immune infiltration of the hub genes were performed.\nResults: A total of 54 common DEGs (2 downregulated and 52 upregulated) were identified. Pathways of neutrophil chemotaxis, neutrophil migration and cytokine and cytokine receptors were enriched in CD and PAD. S100A8, S100A9, S100A12 and CXCR2 were identified as hub genes after validation, with all area under the curve > 0.7 for both CD and PAD. Neutrophil infiltration was associated with upregulation of the hub genes. Pathways of immune processes, including neutrophil activation, neutrophil chemotaxis, neutrophil migration were significantly correlated with high expression of S100A8, S100A9, S100A12 and CXCR2 in both CD and PAD.\nConclusions: This bioinformatic study elucidates S100A8, S100A9, S100A12 and CXCR2 as hub genes for the co-occurrence of Crohn's disease and peripheral artery disease. Inflammation and immune regulation modulated by neutrophil infiltration play a central role in the development of CD and PAD and may be potential targets for diagnosis and treatment.", "claims": [{"id": "claim-method", "statement": "For GSE111889, the data were normalized, and DEGs were found using the R package ‘edgeR’ (19). For GSE120642, the DEGs between healthy and PAD samples were identified using the ‘limma’ package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35795659", "locator": "sections[4] \"Identification of Differentially Expressed Genes With R Software\" paragraph 2", "quote": "For GSE111889, the data were normalized, and DEGs were found using the R package ‘edgeR’ (19). For GSE120642, the DEGs between healthy and PAD samples were identified using the ‘limma’ package."}], "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 authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35795659", "locator": "sections[22] \"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 authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 54 common DEGs (2 downregulated and 52 upregulated) were identified.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35795659", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A total of 54 common DEGs (2 downregulated and 52 upregulated) were identified."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 54 common DEGs (2 downregulated and 52 upregulated) were identified.", "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:35795659"], "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:GSE111889"], "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:GSE111889"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35795659", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2022.896645", "sha256": "sha256:2a06667d1d8db7623b4582095fd89f2e9f0bfdf1d04dfcd49556d633fd08d362", "bytes": 28995, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2022.896645", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9251382", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE111889", "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=GSE111889", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE111889", "version": null, "note": "The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/ Supplementary Material . 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For GSE120642, the DEGs between healthy and PAD samples were identified using the ‘limma’ package."}}, {"id": "method-2", "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": 0.7, "band": "medium", "quote": "limma"}}, {"id": "method-3", "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": []}, "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: edger."}, "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": ["GSE120642", "GSE111889", "GSE95095", "GSE134431"], "resolved_accessions": ["GSE120642", "GSE111889", "GSE95095", "GSE134431"], "statements": ["The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding authors."], "basis": "The paper names GSE120642, GSE111889, GSE95095, GSE134431 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:35795659", "data:geo:GSE111889"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE111889"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:53:57Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 8765, "completion_tokens": 1931, "cached_tokens": 264}}, "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:35795659", "type": "paper", "label": "pmid:35795659"}, {"id": "source:pmid:35795659", "type": "manuscript", "label": "PMID 35795659 full text"}, {"id": "data:geo:GSE111889", "type": "dataset", "label": "GEO GSE111889"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35795659", "type": "paper", "label": "pmid:35795659"}, {"id": "source:pmid:35795659", "type": "manuscript", "label": "PMID 35795659 full text"}, {"id": "data:geo:GSE111889", "type": "dataset", "label": "GEO GSE111889"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35795659", "type": "extraction", "used": ["source:pmid:35795659"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE111889", "type": "accession_resolution", "used": ["data:geo:GSE111889"], "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:35795659", "parent_hash": "sha256:a8295c0711dee196da55a84593f16a95c183d2b4d4bd20ae6734b0b1ce5e6126", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE111889 licence not read", "asset:data:geo:GSE111889 not downloaded", "asset:data:geo:GSE120642 licence not read", "asset:data:geo:GSE120642 not downloaded", "asset:data:geo:GSE134431 licence not read", "asset:data:geo:GSE134431 not downloaded", "asset:data:geo:GSE95095 licence not read", "asset:data:geo:GSE95095 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["ntitative bioinformatic analysis of a public RNA sequencing database. Methods: Datasets of CD (GSE111889", "50 healthy controls and 126 CD patients for RNA sequencing analysis ( Supplementary Table 1 ). Statisti", "889 (18). The GSE120642 dataset contains the RNA-sequencing results of gastrocnemius muscle from 15 heal"], "order_basis": "paper_text_order:483", "id": "assay:1"}, {"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": ["For GSE111889, the data were normalized, and DEGs were found using the R package ‘edgeR’ (19). For GSE120642, the DEGs between healthy and PAD samples were identified using the ‘limma’ package."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}