{"id":"https://openalex.org/W7225745945","doi":"https://doi.org/10.3389/fgene.2026.1814203","title":"Identification of hub genes involved in the pathogenesis of ulcerative colitis: a multi-omics study integrating machine learning, Mendelian randomization, and mediation analysis","display_name":"Identification of hub genes involved in the pathogenesis of ulcerative colitis: a multi-omics study integrating machine learning, Mendelian randomization, and mediation analysis","publication_year":2026,"publication_date":"2026-11-10","ids":{"openalex":"https://openalex.org/W7225745945","doi":"https://doi.org/10.3389/fgene.2026.1814203"},"language":"en","primary_location":{"id":"doi:10.3389/fgene.2026.1814203","doi":"https://doi.org/10.3389/fgene.2026.1814203","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fgene.2026.1814203","pdf_url":null,"source":{"id":"https://openalex.org/S2597340651","display_name":"Frontiers in Genetics","issn_l":"1664-8021","issn":["1664-8021"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","jufo-1","ki-jl-1","norway-1","poland-100","russia-white-list-2","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Genetics","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.3389/fgene.2026.1814203","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5161414574","display_name":"Bo Yang","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Bo Yang","raw_affiliation_strings":["Department of Gastroenterology and Hepatology, Guizhou Aerospace Hospital"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Gastroenterology and Hepatology, Guizhou Aerospace Hospital","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5011196137","display_name":"\u9648\u5fd7\u5e73","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I129708740","display_name":"Fujian Medical University","ror":"https://ror.org/050s6ns64","country_code":"CN","type":"education","lineage":["https://openalex.org/I129708740"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Zhiping Chen","raw_affiliation_strings":["Department of Gastroenterology, Fuzong Clinical Medical College of Fujian Medical University, 900th Hospital of PLA Joint Logistic Support Force"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Gastroenterology, Fuzong Clinical Medical College of Fujian Medical University, 900th Hospital of PLA Joint Logistic Support Force","institution_ids":["https://openalex.org/I129708740"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5161417056","display_name":"Huiling Yu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210140680","display_name":"Affiliated Hospital of Hebei University","ror":"https://ror.org/049vsq398","country_code":"CN","type":"healthcare","lineage":["https://openalex.org/I4210140680"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Huiling Yu","raw_affiliation_strings":["Department of Gastroenterology, Affiliated Hospital of Hebei University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Gastroenterology, Affiliated Hospital of Hebei University","institution_ids":["https://openalex.org/I4210140680"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5161390389","display_name":"Zhu Liu","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I108688024","display_name":"Qingdao University","ror":"https://ror.org/021cj6z65","country_code":"CN","type":"education","lineage":["https://openalex.org/I108688024"]}],"countries":["CN"],"is_corresponding":false,"raw_author_name":"Zhu Liu","raw_affiliation_strings":["Department of Gastroenterology, Shandong Provincial Maternal and Child Healthcare Hospital Affiliated to Qingdao University"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Gastroenterology, Shandong Provincial Maternal and Child Healthcare Hospital Affiliated to Qingdao University","institution_ids":["https://openalex.org/I108688024"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":3150,"currency":"CHF","value_usd":3801},"apc_paid":{"value":3150,"currency":"CHF","value_usd":3801},"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.0,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"17","issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10134","display_name":"Inflammatory Bowel Disease","score":0.9951000213623047,"subfield":{"id":"https://openalex.org/subfields/2715","display_name":"Gastroenterology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10134","display_name":"Inflammatory Bowel Disease","score":0.9951000213623047,"subfield":{"id":"https://openalex.org/subfields/2715","display_name":"Gastroenterology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10261","display_name":"Genetic Associations and Epidemiology","score":0.0010000000474974513,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10887","display_name":"Bioinformatics and Genomic Networks","score":0.0007999999797903001,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[],"concepts":[{"id":"https://openalex.org/C2779901538","wikidata":"https://www.wikidata.org/wiki/Q6816584","display_name":"Mendelian randomization","level":5,"score":0.7301999926567078},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.5857999920845032},{"id":"https://openalex.org/C150194340","wikidata":"https://www.wikidata.org/wiki/Q26972","display_name":"Gene expression","level":3,"score":0.5151000022888184},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.51419997215271},{"id":"https://openalex.org/C162317418","wikidata":"https://www.wikidata.org/wiki/Q252857","display_name":"Transcriptome","level":4,"score":0.47290000319480896},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.454800009727478},{"id":"https://openalex.org/C18431079","wikidata":"https://www.wikidata.org/wiki/Q1502169","display_name":"Gene expression profiling","level":4,"score":0.4465000033378601},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.4449000060558319},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.4244999885559082},{"id":"https://openalex.org/C116834253","wikidata":"https://www.wikidata.org/wiki/Q2039217","display_name":"Identification (biology)","level":2,"score":0.421999990940094},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.3968999981880188},{"id":"https://openalex.org/C179420905","wikidata":"https://www.wikidata.org/wiki/Q223871","display_name":"Mediation","level":2,"score":0.38670000433921814},{"id":"https://openalex.org/C168393362","wikidata":"https://www.wikidata.org/wiki/Q5421706","display_name":"Expression quantitative trait loci","level":5,"score":0.36579999327659607},{"id":"https://openalex.org/C2991772755","wikidata":"https://www.wikidata.org/wiki/Q751748","display_name":"Gene interaction","level":3,"score":0.3612000048160553},{"id":"https://openalex.org/C67339327","wikidata":"https://www.wikidata.org/wiki/Q1502576","display_name":"Gene regulatory network","level":4,"score":0.3569999933242798},{"id":"https://openalex.org/C186836561","wikidata":"https://www.wikidata.org/wiki/Q1931516","display_name":"Microarray","level":4,"score":0.3515999913215637},{"id":"https://openalex.org/C8415881","wikidata":"https://www.wikidata.org/wiki/Q6839217","display_name":"Microarray analysis techniques","level":4,"score":0.329800009727478},{"id":"https://openalex.org/C165864922","wikidata":"https://www.wikidata.org/wiki/Q411391","display_name":"Regulation of gene expression","level":3,"score":0.32839998602867126},{"id":"https://openalex.org/C90559484","wikidata":"https://www.wikidata.org/wiki/Q778379","display_name":"Expression (computer science)","level":2,"score":0.3273000121116638},{"id":"https://openalex.org/C106208931","wikidata":"https://www.wikidata.org/wiki/Q1098876","display_name":"Genome-wide association study","level":5,"score":0.3269999921321869},{"id":"https://openalex.org/C152724338","wikidata":"https://www.wikidata.org/wiki/Q909442","display_name":"KEGG","level":5,"score":0.3183000087738037},{"id":"https://openalex.org/C2780942790","wikidata":"https://www.wikidata.org/wiki/Q372016","display_name":"Pathogenesis","level":2,"score":0.30640000104904175},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.2969000041484833},{"id":"https://openalex.org/C2778260677","wikidata":"https://www.wikidata.org/wiki/Q917447","display_name":"Inflammatory bowel disease","level":3,"score":0.29429998993873596},{"id":"https://openalex.org/C2780479503","wikidata":"https://www.wikidata.org/wiki/Q1477","display_name":"Ulcerative colitis","level":3,"score":0.28690001368522644},{"id":"https://openalex.org/C2778022302","wikidata":"https://www.wikidata.org/wiki/Q18207329","display_name":"Gene co-expression network","level":5,"score":0.2808000147342682},{"id":"https://openalex.org/C186413461","wikidata":"https://www.wikidata.org/wiki/Q744727","display_name":"Genetic association","level":5,"score":0.272599995136261},{"id":"https://openalex.org/C81941488","wikidata":"https://www.wikidata.org/wiki/Q853421","display_name":"Quantitative trait locus","level":3,"score":0.27160000801086426},{"id":"https://openalex.org/C95371953","wikidata":"https://www.wikidata.org/wiki/Q591745","display_name":"DNA microarray","level":4,"score":0.2655999958515167},{"id":"https://openalex.org/C106934330","wikidata":"https://www.wikidata.org/wiki/Q1971873","display_name":"Trait","level":2,"score":0.2554999887943268},{"id":"https://openalex.org/C69991583","wikidata":"https://www.wikidata.org/wiki/Q1423575","display_name":"Candidate gene","level":3,"score":0.25519999861717224}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.3389/fgene.2026.1814203","doi":"https://doi.org/10.3389/fgene.2026.1814203","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fgene.2026.1814203","pdf_url":null,"source":{"id":"https://openalex.org/S2597340651","display_name":"Frontiers in Genetics","issn_l":"1664-8021","issn":["1664-8021"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","jufo-1","ki-jl-1","norway-1","poland-100","russia-white-list-2","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Genetics","raw_type":"journal-article"}],"best_oa_location":{"id":"doi:10.3389/fgene.2026.1814203","doi":"https://doi.org/10.3389/fgene.2026.1814203","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fgene.2026.1814203","pdf_url":null,"source":{"id":"https://openalex.org/S2597340651","display_name":"Frontiers in Genetics","issn_l":"1664-8021","issn":["1664-8021"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","jufo-1","ki-jl-1","norway-1","poland-100","russia-white-list-2","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Genetics","raw_type":"journal-article"},"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":46,"referenced_works":["https://openalex.org/W1490161904","https://openalex.org/W1972696558","https://openalex.org/W2049166142","https://openalex.org/W2087401044","https://openalex.org/W2613373507","https://openalex.org/W2749325548","https://openalex.org/W3094540111","https://openalex.org/W3128459990","https://openalex.org/W4205389315","https://openalex.org/W4294216483","https://openalex.org/W4304481091","https://openalex.org/W4308834893","https://openalex.org/W4309858834","https://openalex.org/W4377292543","https://openalex.org/W4384401175","https://openalex.org/W4385270799","https://openalex.org/W4385422413","https://openalex.org/W4390806091","https://openalex.org/W4392465547","https://openalex.org/W4394015388","https://openalex.org/W4396906992","https://openalex.org/W4400691443","https://openalex.org/W4401435515","https://openalex.org/W4402498097","https://openalex.org/W4403451544","https://openalex.org/W4405951689","https://openalex.org/W4407229053","https://openalex.org/W4409202859","https://openalex.org/W4411095535","https://openalex.org/W4411501046","https://openalex.org/W4412493329","https://openalex.org/W4412521230","https://openalex.org/W4413969862","https://openalex.org/W4414193455","https://openalex.org/W4414354174","https://openalex.org/W4414520104","https://openalex.org/W4414524046","https://openalex.org/W4415205682","https://openalex.org/W4415479133","https://openalex.org/W4416099212","https://openalex.org/W4416226166","https://openalex.org/W4416329406","https://openalex.org/W4416705560","https://openalex.org/W4416933323","https://openalex.org/W7125702035","https://openalex.org/W7164340670"],"related_works":[],"abstract_inverted_index":{"Background":[0],"Ulcerative":[1],"colitis":[2],"(UC)":[3],"is":[4],"a":[5,11,138,278],"chronic":[6],"inflammatory":[7],"bowel":[8],"disease":[9],"with":[10,107,187],"steadily":[12],"increasing":[13],"global":[14],"prevalence,":[15],"yet":[16],"its":[17],"precise":[18],"molecular":[19],"mechanisms":[20],"remain":[21],"incompletely":[22],"understood.":[23],"This":[24,264],"study":[25,265],"aimed":[26],"to":[27,42,79,96,126,249],"identify":[28,80],"potential":[29,36,98,128,163],"diagnostic":[30,164],"biomarkers":[31,165,270],"for":[32,166,255],"UC":[33,188,240,290],"and":[34,56,73,105,155,173,184,239,271,289],"explore":[35],"metabolite-mediated":[37,129],"pathways":[38],"linking":[39],"gene":[40,63,103],"expression":[41,46,60,104,134,186,238,288],"UC.":[43],"Methods":[44],"Gene":[45,52],"datasets":[47],"were":[48],"obtained":[49],"from":[50],"the":[51,108,114,234,260,282],"Expression":[53],"Omnibus":[54],"database":[55],"analyzed":[57],"using":[58],"differential":[59],"analysis,":[61,72,150,154],"weighted":[62],"co-expression":[64],"network":[65,71,153],"analysis":[66,87,122,227],"(WGCNA),":[67],"protein\u2013protein":[68],"interaction":[69],"(PPI)":[70],"multiple":[74],"machine":[75],"learning":[76],"(ML)":[77],"algorithms":[78],"key":[81],"UC-associated":[82,268],"genes.":[83],"Mendelian":[84],"randomization":[85],"(MR)":[86],"based":[88],"on":[89],"cis-expression":[90],"quantitative":[91],"trait":[92],"loci":[93],"was":[94,123,135],"performed":[95],"assess":[97],"causal":[99],"associations":[100,181],"between":[101,236,285],"candidate":[102,269,279],"UC,":[106],"random-effects":[109],"inverse-variance-weighted":[110],"method":[111],"used":[112],"as":[113],"primary":[115,176],"analytical":[116],"approach.":[117],"Exploratory":[118,223],"two-step":[119,224],"MR":[120,177,225],"mediation":[121,226],"subsequently":[124],"conducted":[125],"investigate":[127],"pathways.":[130],"In":[131],"addition,":[132],"core-gene":[133],"assessed":[136],"in":[137],"dextran":[139],"sulfate":[140],"sodium-induced":[141],"mouse":[142],"model":[143,158],"of":[144,182,259,281],"colitis.":[145],"Results":[146],"By":[147],"integrating":[148],"transcriptomic":[149],"WGCNA,":[151],"PPI":[152],"127":[156],"ML":[157],"combinations,":[159],"we":[160],"identified":[161,266],"six":[162,267],"UC:":[167],"CXCL1,":[168],"CXCL2,":[169],"CXCR2,":[170],"ENPP3,":[171],"MMP1,":[172],"PPBP.":[174],"The":[175],"analyses":[178],"showed":[179],"inverse":[180,283],"CXCR2":[183,237,287],"ENPP3":[185],"risk":[189],"(CXCR2:":[190],"OR":[191,205],"=":[192,198,206,212,244,252],"0.5792,":[193],"95%":[194,208,246],"CI:":[195,209,247],"0.4596\u20130.7299;":[196],"P":[197,211,220,251],"3.69":[199],"\u00d7":[200,214],"10":[201,215],"\u22126":[202],";":[203,217],"ENPP3:":[204],"0.3111,":[207],"0.1987\u20130.4871;":[210],"3.33":[213],"\u22127":[216],"both":[218],"BH-adjusted":[219],"<":[221],"0.001).":[222],"suggested":[228,272],"that":[229,273],"arachidonoylcholine":[230,275],"may":[231,276],"partially":[232],"mediate":[233],"association":[235,284],"(indirect":[241],"effect:":[242],"\u03b2":[243],"\u22120.0566,":[245],"\u22120.1041":[248],"\u22120.0092;":[250],"0.0193),":[253],"accounting":[254],"an":[256],"estimated":[257],"10.37%":[258],"total":[261],"effect.":[262],"Conclusion":[263],"plasma":[274],"be":[277],"mediator":[280],"whole-blood":[286],"risk.":[291],"These":[292],"findings":[293],"require":[294],"further":[295],"validation":[296],"through":[297],"functional":[298],"experiments.":[299]},"counts_by_year":[],"updated_date":"2026-11-11T12:16:26.678958","created_date":"2026-11-11T00:00:00"}