Identification of key genes and biological processes contributing to colitis associated dysplasia in ulcerative colitis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33987007", "kind": "science-record", "revision": 5, "content_hash": "sha256:18f22f470ad8b96218639c7e2accf4c3cdfb42b80da636fe73eb11050b94af2b", "created_at": "2026-11-01T15:41:35Z", "updated_at": "2026-11-01T22:03:45Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of key genes and biological processes contributing to colitis associated dysplasia in ulcerative colitis.", "doi": "10.7717/peerj.11321", "pmid": "33987007", "authors": ["Di Zhang", "Pengguang Yan", "Taotao Han", "Xiaoyun Cheng", "Jingnan Li"], "journal": "PeerJ", "year": 2021, "abstract": "BACKGROUND: Ulcerative colitis-associated colorectal cancer (UC-CRC) is a life-threatening complication of ulcerative colitis (UC). The mechanisms underlying UC-CRC remain to be elucidated. The purpose of this study was to explore the key genes and biological processes contributing to colitis-associated dysplasia (CAD) or carcinogenesis in UC via database mining, thus offering opportunities for early prediction and intervention of UC-CRC.\nMETHODS: Microarray datasets (GSE47908 and GSE87466) were downloaded from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) between groups of GSE47908 were identified using the \"limma\" R package. Weighted gene co-expression network analysis (WGCNA) based on DEGs between the CAD and control groups was conducted subsequently. Functional enrichment analysis was performed, and hub genes of selected modules were identified using the \"clusterProfiler\" R package. Single-gene gene set enrichment analysis (GSEA) was conducted to predict significant biological processes and pathways associated with the specified gene.\nRESULTS: Six functional modules were identified based on 4929 DEGs. Green and blue modules were selected because of their consistent correlation with UC and CAD, and the highest correlation coefficient with the progress of UC-associated carcinogenesis. Functional enrichment analysis revealed that genes of these two modules were significantly enriched in biological processes, including mitochondrial dysfunction, cell-cell junction, and immune responses. However, GSEA based on differential expression analysis between sporadic colorectal cancer (CRC) and normal controls from The Cancer Genome Atlas (TCGA) indicated that mitochondrial dysfunction may not be the major carcinogenic mechanism underlying sporadic CRC. Thirteen hub genes (SLC25A3, ACO2, AIFM1, ATP5A1, DLD, TFE3, UQCRC1, ADIPOR2, SLC35D1, TOR1AIP1, PRR5L, ATOX1, and DTX3) were identified. Their expression trends were validated in UC patients of GSE87466, and their potential carcinogenic effects in UC were supported by their known functions and other relevant studies reported in the literature. Single-gene GSEA indicated that biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to angiogenesis and immune response were positively correlated with the upregulation of TFE3, whereas those related to mitochondrial function and energy metabolism were negatively correlated with the upregulation of TFE3.\nCONCLUSIONS: Using WGCNA, this study found two gene modules that were significantly correlated with CAD, of which 13 hub genes were identified as the potential key genes. The critical biological processes in which the genes of these two modules were significantly enriched include mitochondrial dysfunction, cell-cell junction, and immune responses. TFE3, a transcription factor related to mitochondrial function and cancers, may play a central role in UC-associated carcinogenesis.", "claims": [{"id": "claim-method", "statement": "The expression profiles of DEGs between CAD and control group were extracted to construct weighted gene co-expression network using R package “WGCNA” (Langfelder & Horvath, 2008; Zhang & Horvath, 2005).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33987007", "locator": "sections[5] \"WGCNA\" paragraph 2", "quote": "The expression profiles of DEGs between CAD and control group were extracted to construct weighted gene co-expression network using R package “WGCNA” (Langfelder & Horvath, 2008; Zhang & Horvath, 2005)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The following information was supplied regarding data availability:\nThe code is available in the Supplementary File. The data for analysis and validation are available at NCBI GEO: GSE47908 and GSE87466.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33987007", "locator": "sections[28] \"Data Availability Statement\" paragraphs 1-3", "quote": "The following information was supplied regarding data availability:\nThe code is available in the Supplementary File. The data for analysis and validation are available at NCBI GEO: GSE47908 and GSE87466."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:33987007"], "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:GSE47908"], "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:GSE47908"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33987007", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.7717/peerj.11321", "sha256": "sha256:a2020394a1d27eae58f715e7e37a8c34dd765c0c0ea1aaebaff9390f742b70a9", "bytes": 46336, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.7717/peerj.11321", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8086577", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE47908", "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=GSE47908", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE47908", "version": null, "note": "The following information was supplied regarding data availability:\nThe code is available in the Supplementary File. 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Wang et al., 2013)", "No (Laiho et al., 2003)"], ["AIFM1", "Apoptosis-inducing factor 1, mitochondrial", "Regulate apoptosis, and involve in mitochondrial respiratory", "Yes (Liu et al., 2018; Rao et al., 2019)", "Yes (Millan & Huerta, 2009)"], ["ATP5A1", "ATP synthase subunit alpha, mitochondrial", "A component of the mitochondrial complex V in the respiratory chain, involve in ATP synthesis", "Yes (Bruggemann et al., 2017)", "Yes (Seth et al., 2009)"], ["DLD", "Dihydrolipoyl dehydrogenase, mitochondrial", "Function as a dehydrogenase regulating energy metabolism, or as a protease", "Yes (Khalil, 2007)", "No"], ["TFE3", "Transcription factor binding to IGHM enhancer 3", "Function as transcription factor, regulate many biological processes, such as energy metabolism,lysosomal biogenesis and immune response", "Yes (Linehan et al., 2019; Perera et al., 2015)", "No"], ["UQCRC1", "Cytochrome b-c1 complex subunit 1, mitochondrial", "A component of the complex III in the respiratory chain, involve in ATP synthesis", "Yes (Wang et al., 2020)", "Yes (Li et al., 2019)"], ["ADIPOR2", "Adiponectin receptor protein 2", "Regulates glucose and lipid metabolism, mediate increased AMPK and PPAR-alpha ligand activities", "Yes (Chung et al., 2017)", "Yes (Byeon et al., 2010)"], ["SLC35D1", "UDP-glucuronic acid/UDP-N-acetylgalactosamine transporter", "Transport both UDP-glucuronic acid and UDP-N-acetylgalactosamine to ER lumen, participate in glucuronidation and/or chondroitin sulfate biosynthesis", "Yes (Viola et al., 2017)", "No"], ["TOR1AIP1", "Torsin-1A-interacting protein 1", "Localize to the inner nuclear membrane, maintain the attachment of the nuclear membrane to nuclear lamina during cell division", "No", "No"], ["PRR5L", "Proline-rich protein 5-like", "Associate with mTORC2 complex that regulate cellular processes including survival and cytoskeleton organization", "No (Thedieck et al., 2007)", "No"], ["ATOX1", "Copper transport protein", "Bind and deliver cytosolic copper to copper ATPase proteins, and be important in cellular antioxidant defense", "Yes (Karginova et al., 2019; Kim et al., 2019)", "Yes (Jana et al., 2020)"], ["DTX3", "Deltex E3 ubiquitin ligase 3", "Function as an E3 ubiquitin ligase, regulate Notch signaling", "Yes (Ding et al., 2020)", "No"]], "row_count": 14, "column_count": 5, "numeric_cells": 27, "header_rows": 1, "locator": "section[13]/table-wrap[1]#table-1"}}], "gaps": ["asset:data:geo:GSE47908 not downloaded", "asset:data:geo:GSE47908 licence not read", "asset:data:geo:GSE87466 not downloaded", "asset:data:geo:GSE87466 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": 0.7, "band": "medium", "quote": "limma"}}, {"id": "method-2", "family": null, "specific": null, "label": "Weighted gene co-expression network analysis (WGCNA)", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The expression profiles of DEGs between CAD and control group were extracted to construct weighted gene co-expression network using R package “WGCNA” (Langfelder & Horvath, 2008; Zhang & Horvath, 2005)."}}], "targets": [], "gaps": ["method.reader_named_unmapped"]}, "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": ["GSE47908", "GSE87466"], "resolved_accessions": ["GSE47908", "GSE87466"], "statements": ["The following information was supplied regarding data availability:\nThe code is available in the Supplementary File. The data for analysis and validation are available at NCBI GEO: GSE47908 and GSE87466."], "basis": "The paper names GSE47908, GSE87466 in NCBI 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:33987007", "data:geo:GSE47908", "asset:table:pmid:33987007:1"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE47908"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:29:59Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 36707, "completion_tokens": 1350, "cached_tokens": 784}}, "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:33987007", "type": "paper", "label": "pmid:33987007"}, {"id": "source:pmid:33987007", "type": "manuscript", "label": "PMID 33987007 full text"}, {"id": "data:geo:GSE47908", "type": "dataset", "label": "GEO GSE47908"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33987007", "type": "paper", "label": "pmid:33987007"}, {"id": "source:pmid:33987007", "type": "manuscript", "label": "PMID 33987007 full text"}, {"id": "data:geo:GSE47908", "type": "dataset", "label": "GEO GSE47908"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33987007", "type": "extraction", "used": ["source:pmid:33987007"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE47908", "type": "accession_resolution", "used": ["data:geo:GSE47908"], "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:33987007", "parent_hash": "sha256:35039fe05cdf7a3d8a44c02876a7905fce95a856976770a528a17dd7ecb96f97", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE47908 licence not read", "asset:data:geo:GSE47908 not downloaded", "asset:data:geo:GSE87466 licence not read", "asset:data:geo:GSE87466 not downloaded", "execution.not_run", "method.reader_named_unmapped", "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": ["diction and intervention of UC-CRC. 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