Identification of AKR1B10 as a key gene in primary biliary cholangitis by integrated bioinformatics analysis and experimental validation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36845547", "kind": "science-record", "revision": 4, "content_hash": "sha256:907d5d1033f88fc264ec16c2321bcd0fe143b7751de558fd0f8907313d964d30", "created_at": "2026-11-01T19:01:28Z", "updated_at": "2026-11-01T22:51:23Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of AKR1B10 as a key gene in primary biliary cholangitis by integrated bioinformatics analysis and experimental validation.", "doi": "10.3389/fmolb.2023.1124956", "pmid": "36845547", "authors": ["Huiwen Wang", "Jian Zhang", "Jinqing Liu", "Yongfang Jiang", "Lei Fu", "Shifang Peng"], "journal": "Frontiers in molecular biosciences", "year": 2023, "abstract": "Background: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease that eventually progresses to cirrhosis and hepatocellular carcinoma (HCC) in the absence of proper treatment. However, Gene expression and molecular mechanisms involved in the pathogenesis of PBC have not been completely elucidated. Methods: Microarray expression profiling dataset GSE61260 was downloaded from the Gene Expression Omnibus (GEO) database. Data were normalized to screen differentially expressed genes (DEGs) using the limma package in R. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed. A protein-protein interaction (PPI) network was constructed to identify hub genes and an integrative regulatory network of transcriptional factor-DEG-microRNA was established. Gene Set Enrichment Analysis (GSEA) was used to analyze differences in biological states for groups with different expressions of aldo-keto reductase family 1 member B10 (AKR1B10). Immunohistochemistry (IHC) analysis was performed to validate the expression of hepatic AKR1B10 in patients with PBC. The association of hepatic AKR1B10 levels with clinical parameters was evaluated using one-way analysis of variance (ANOVA) and Pearson's correlation analysis. Results: This study identified 22 upregulated and 12 downregulated DEGs between patients with PBC and healthy controls. GO and KEGG analysis revealed that DEGs were mainly enriched in immune reactions. AKR1B10 was identified as a key gene and was further analyzed by screening out hub genes from the PPI network. GSEA analysis indicated that high expression of AKR1B10 might promote PBC to develop into HCC. Immunohistochemistry results verified the increased expression of hepatic AKR1B10 in patients with PBC and demonstrated its positive correlation with the severity of PBC. Conclusion: AKR1B10 was identified as a hub gene in PBC by integrated bioinformatics analysis and clinical validation. The increase of AKR1B10 expression in patients with PBC was associated with disease severity and might promote the progression of PBC to HCC.", "claims": [{"id": "claim-method", "statement": "DEGs were screened out in all datasets using the limma package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36845547", "locator": "sections[4] \"2.2 Identification of DEGs\" paragraph 2", "quote": "DEGs were screened out in all datasets 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:36845547", "locator": "sections[21] \"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": "Based on the limma package in R language (|logFC| ≥1, adj. p-value < .05), 34 DEGs were identified, including 22 up- and 12 downregulated DEGs (Supplementary Table S2).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36845547", "locator": "sections[13] \"3.2 Identification of DEGs\" paragraph 2", "quote": "Based on the limma package in R language (|logFC| ≥1, adj. p-value < .05), 34 DEGs were identified, including 22 up- and 12 downregulated DEGs (Supplementary Table S2)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Based on the limma package in R language (|logFC| ≥1, adj. p-value < .05), 34 DEGs were identified, including 22 up- and 12 downregulated DEGs (Supplementary Table S2).", "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:36845547"], "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:GSE61260"], "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:GSE61260"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36845547", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fmolb.2023.1124956", "sha256": "sha256:7cd330b75a051a12c703bac55b0172af9558cdeecae6ce482fc954ae8a8ecb25", "bytes": 32120, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fmolb.2023.1124956", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9947156", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE61260", "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=GSE61260", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE61260", "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, further inquiries can be directed to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1501013", "GSM1501014", "GSM1501015", "GSM1501016", "GSM1501017", "GSM1501018", "GSM1501019", "GSM1501020", "GSM1501021", "GSM1501022", "GSM1501023", "GSM1501024", "GSM1501025", "GSM1501026", "GSM1501027", "GSM1501028", "GSM1501029", "GSM1501030", "GSM1501031", "GSM1501032", "GSM1501033", "GSM1501034", "GSM1501035", "GSM1501036", "GSM1501037", "GSM1501038", "GSM1501039", "GSM1501040", "GSM1501041", "GSM1501042", "GSM1501043", "GSM1501044", "GSM1501045", "GSM1501046", "GSM1501047", "GSM1501048", "GSM1501049", "GSM1501050", "GSM1501051", "GSM1501052", "GSM1501053", "GSM1501054", "GSM1501055", "GSM1501056", "GSM1501057", "GSM1501058", "GSM1501059", "GSM1501060", "GSM1501061", "GSM1501062", "GSM1501063", "GSM1501064", "GSM1501065", "GSM1501066", "GSM1501067", "GSM1501068", "GSM1501069", "GSM1501070", "GSM1501071", "GSM1501072", "GSM1501073", "GSM1501074", "GSM1501075", "GSM1501076", "GSM1501077", "GSM1501078", "GSM1501079", "GSM1501080", "GSM1501081", "GSM1501082", "GSM1501083", "GSM1501084", "GSM1501085", "GSM1501086", "GSM1501087", "GSM1501088", "GSM1501089", "GSM1501090", "GSM1501091", "GSM1501092", "GSM1501093", "GSM1501094", "GSM1501095", "GSM1501096", "GSM1501097", "GSM1501098", "GSM1501099", "GSM1501100", "GSM1501101", "GSM1501102", "GSM1501103", "GSM1501104", "GSM1501105", "GSM1501106", "GSM1501107", "GSM1501108", "GSM1501109", "GSM1501110", "GSM1501111", "GSM1501112", "GSM1501113", "GSM1501114", "GSM1501115", "GSM1501116", "GSM1501117", "GSM1501118", "GSM1501119", "GSM1501120", "GSM1501121", "GSM1501122", "GSM1501123", "GSM1501124", "GSM1501125", "GSM1501126", "GSM1501127", "GSM1501128", "GSM1501129", "GSM1501130", "GSM1501131", "GSM1501132", "GSM1501133", "GSM1501134", "GSM1501135", "GSM1501136", "GSM1501137", "GSM1501138", "GSM1501139", "GSM1501140", "GSM1501141", "GSM1501142", "GSM1501143", "GSM1501144", "GSM1501145", "GSM1501146"], "sample_count": 134, "group_sizes": null, "group_sizes_basis": null, "platform": "11532", "taxon": "Homo sapiens", "title": "Human liver gene expression data from subjects of varying ages", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE61260 not downloaded", "asset:data:geo:GSE61260 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": "DEGs were screened out in all datasets using the limma package."}}, {"id": "method-2", "family": "group_comparison", "specific": "anova", "label": "Group comparison", "dsl_operations": ["group_summary", "welch_t", "bootstrap_mean_difference", "group_comparison_anova"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.7, "band": "medium", "quote": "analysis of variance"}}, {"id": "method-3", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.7, "band": "medium", "quote": "Pearson's correlation"}}, {"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"}}, {"id": "method-5", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "GO enrichment"}}], "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": ["GSE61260"], "resolved_accessions": ["GSE61260"], "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 GSE61260 in Gene Expression Omnibus (GEO) database 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:36845547", "data:geo:GSE61260"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE61260"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:31:58Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 9918, "completion_tokens": 1001, "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:36845547", "type": "paper", "label": "pmid:36845547"}, {"id": "source:pmid:36845547", "type": "manuscript", "label": "PMID 36845547 full text"}, {"id": "data:geo:GSE61260", "type": "dataset", "label": "GEO GSE61260"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36845547", "type": "paper", "label": "pmid:36845547"}, {"id": "source:pmid:36845547", "type": "manuscript", "label": "PMID 36845547 full text"}, {"id": "data:geo:GSE61260", "type": "dataset", "label": "GEO GSE61260"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36845547", "type": "extraction", "used": ["source:pmid:36845547"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE61260", "type": "accession_resolution", "used": ["data:geo:GSE61260"], "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:36845547", "parent_hash": "sha256:7212cbe93a3241c63ba7dcc0c8323a03c2d89370981a0f7dc78832e125cf3352", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE61260 licence not read", "asset:data:geo:GSE61260 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": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["ave not been completely elucidated. Methods: Microarray expression profiling dataset GSE61260 was do"], "order_basis": "paper_text_order:420", "id": "assay:1"}, {"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["eto reductase family 1 member B10 (AKR1B10). Immunohistochemistry (IHC) analysis was performed to validate the", "R1B10 might promote PBC to develop into HCC. Immunohistochemistry results verified the increased expression of", "member B10 (AKR1B10). Immunohistochemistry (IHC) analysis was performed to validate the expr", "nical features of patients. Histological and immunohistochemistry analyses of serial liver sections from patie"], "order_basis": "paper_text_order:1113", "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": ["DEGs were screened out in all datasets using the limma package."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}