{"id":"https://openalex.org/W7225327735","doi":"https://doi.org/10.64898/2026.11.04.764243","title":"Transportability of mouse gene knockout models to human complex phenotypes","display_name":"Transportability of mouse gene knockout models to human complex phenotypes","publication_year":2026,"publication_date":"2026-11-05","ids":{"openalex":"https://openalex.org/W7225327735","doi":"https://doi.org/10.64898/2026.11.04.764243"},"language":"en","primary_location":{"id":"doi:10.64898/2026.11.04.764243","doi":"https://doi.org/10.64898/2026.11.04.764243","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.04.764243","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/11/05/2026.11.04.764243.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/11/05/2026.11.04.764243.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5023038797","display_name":"Laurence J Howe","orcid":"https://orcid.org/0000-0002-2819-9686","observed_orcids":["https://orcid.org/0000-0002-2819-9686"]},"institutions":[{"id":"https://openalex.org/I188950975","display_name":"GlaxoSmithKline (United Kingdom)","ror":"https://ror.org/01xsqw823","country_code":"GB","type":"company","lineage":["https://openalex.org/I188950975"]}],"countries":["GB"],"is_corresponding":true,"raw_author_name":"Laurence J Howe","raw_affiliation_strings":["Translational Sciences, GSK, Stevenage, UK"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Translational Sciences, GSK, Stevenage, UK","institution_ids":["https://openalex.org/I188950975"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5042573176","display_name":"Sara E. Wells","orcid":"https://orcid.org/0000-0002-0572-0600","observed_orcids":["https://orcid.org/0000-0002-0572-0600"]},"institutions":[{"id":"https://openalex.org/I2801081054","display_name":"The Francis Crick Institute","ror":"https://ror.org/04tnbqb63","country_code":"GB","type":"facility","lineage":["https://openalex.org/I2801081054"]},{"id":"https://openalex.org/I4210086857","display_name":"Mary Lyon Centre at MRC Harwell","ror":"https://ror.org/0001h1y25","country_code":"GB","type":"facility","lineage":["https://openalex.org/I4210086857","https://openalex.org/I4210087105","https://openalex.org/I90344618"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Sara Wells","raw_affiliation_strings":["The Francis Crick Institute, 1 Midland Road, London, NW1 1AT","The Mary Lyon Centre at MRC Harwell, Harwell Campus, Didcot, OX11 0RD, UK"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"The Francis Crick Institute, 1 Midland Road, London, NW1 1AT","institution_ids":["https://openalex.org/I2801081054"]},{"raw_affiliation_string":"The Mary Lyon Centre at MRC Harwell, Harwell Campus, Didcot, OX11 0RD, UK","institution_ids":["https://openalex.org/I4210086857"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5061002857","display_name":"Neil M Davies","orcid":"https://orcid.org/0000-0002-2460-0508","observed_orcids":["https://orcid.org/0000-0002-2460-0508"]},"institutions":[{"id":"https://openalex.org/I204778367","display_name":"Norwegian University of Science and Technology","ror":"https://ror.org/05xg72x27","country_code":"NO","type":"education","lineage":["https://openalex.org/I204778367"]},{"id":"https://openalex.org/I45129253","display_name":"University College London","ror":"https://ror.org/02jx3x895","country_code":"GB","type":"education","lineage":["https://openalex.org/I124357947","https://openalex.org/I45129253"]}],"countries":["GB","NO"],"is_corresponding":false,"raw_author_name":"Neil M Davies","raw_affiliation_strings":["Department of Public Health and Nursing, Norwegian University of Science and Technology, Norway","Department of Statistical Science, University College London, London WC1E 6BT, UK","Division of Psychiatry, University College London, London, UK"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Public Health and Nursing, Norwegian University of Science and Technology, Norway","institution_ids":["https://openalex.org/I204778367"]},{"raw_affiliation_string":"Department of Statistical Science, University College London, London WC1E 6BT, UK","institution_ids":["https://openalex.org/I45129253"]},{"raw_affiliation_string":"Division of Psychiatry, University College London, London, UK","institution_ids":["https://openalex.org/I45129253"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5158754592","display_name":"Sam M. Lockhart","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I188950975","display_name":"GlaxoSmithKline (United Kingdom)","ror":"https://ror.org/01xsqw823","country_code":"GB","type":"company","lineage":["https://openalex.org/I188950975"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"Sam M Lockhart","raw_affiliation_strings":["Translational Sciences, GSK, Stevenage, UK"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Translational Sciences, GSK, Stevenage, UK","institution_ids":["https://openalex.org/I188950975"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5013184354","display_name":"George Davey Smith","orcid":"https://orcid.org/0000-0002-1407-8314","observed_orcids":["https://orcid.org/0000-0002-1407-8314"]},"institutions":[{"id":"https://openalex.org/I36234482","display_name":"University of Bristol","ror":"https://ror.org/0524sp257","country_code":"GB","type":"education","lineage":["https://openalex.org/I36234482"]},{"id":"https://openalex.org/I4387155195","display_name":"MRC Integrative Epidemiology Unit","ror":"https://ror.org/030qtrs05","country_code":"GB","type":"facility","lineage":["https://openalex.org/I36234482","https://openalex.org/I4210087105","https://openalex.org/I4387155195","https://openalex.org/I90344618"]}],"countries":["GB"],"is_corresponding":false,"raw_author_name":"George Davey Smith","raw_affiliation_strings":["MRC-IEU, University of Bristol, Bristol, UK"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"MRC-IEU, University of Bristol, Bristol, UK","institution_ids":["https://openalex.org/I36234482","https://openalex.org/I4387155195"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":7,"corresponding_author_ids":["https://openalex.org/A5023038797"],"corresponding_institution_ids":["https://openalex.org/I188950975"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10887","display_name":"Bioinformatics and Genomic Networks","score":0.5131999850273132,"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"}},"topics":[{"id":"https://openalex.org/T10887","display_name":"Bioinformatics and Genomic Networks","score":0.5131999850273132,"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"}},{"id":"https://openalex.org/T10261","display_name":"Genetic Associations and Epidemiology","score":0.260699987411499,"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/T11710","display_name":"Biomedical Text Mining and Ontologies","score":0.029999999329447746,"subfield":{"id":"https://openalex.org/subfields/2718","display_name":"Health Informatics"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/orthologs","display_name":"orthologs","score":0.7239999771118164},{"id":"https://openalex.org/keywords/international-mouse-phenotyping-consortium","display_name":"International Mouse Phenotyping Consortium","score":0.9390000104904175},{"id":"https://openalex.org/keywords/uk-biobank","display_name":"UK Biobank","score":0.9089999794960022},{"id":"https://openalex.org/keywords/cholesterol","display_name":"cholesterol","score":0.3409999907016754},{"id":"https://openalex.org/keywords/lymphocyte-count","display_name":"lymphocyte count","score":0.9190000295639038},{"id":"https://openalex.org/keywords/anthropometric-traits","display_name":"anthropometric traits","score":0.8960000276565552},{"id":"https://openalex.org/keywords/body-fat","display_name":"fat mass","score":0.6679999828338623},{"id":"https://openalex.org/keywords/body-mass-index","display_name":"body mass index","score":0.9580000042915344},{"id":"https://openalex.org/keywords/glucose","display_name":"glucose","score":0.46799999475479126},{"id":"https://openalex.org/keywords/diabetes-mellitus","display_name":"diabetes mellitus","score":0.9729999899864197},{"id":"https://openalex.org/keywords/model-validation","display_name":"model validation","score":0.4830000102519989}],"concepts":[{"id":"https://openalex.org/C127716648","wikidata":"https://www.wikidata.org/wiki/Q104053","display_name":"Phenotype","level":3,"score":0.7897999882698059},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.6974999904632568},{"id":"https://openalex.org/C77957584","wikidata":"https://www.wikidata.org/wiki/Q1133550","display_name":"Gene knockout","level":3,"score":0.6380000114440918},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.5231000185012817},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.46880000829696655},{"id":"https://openalex.org/C182704531","wikidata":"https://www.wikidata.org/wiki/Q1364740","display_name":"Knockout mouse","level":3,"score":0.4221999943256378},{"id":"https://openalex.org/C169899063","wikidata":"https://www.wikidata.org/wiki/Q2842787","display_name":"Laboratory mouse","level":3,"score":0.4196999967098236},{"id":"https://openalex.org/C2779343474","wikidata":"https://www.wikidata.org/wiki/Q3109175","display_name":"Context (archaeology)","level":2,"score":0.3926999866962433},{"id":"https://openalex.org/C2988867146","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Human disease","level":3,"score":0.3822000026702881},{"id":"https://openalex.org/C111829913","wikidata":"https://www.wikidata.org/wiki/Q211083","display_name":"Gene targeting","level":3,"score":0.3734000027179718},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.3601999878883362},{"id":"https://openalex.org/C84597430","wikidata":"https://www.wikidata.org/wiki/Q106227","display_name":"Locus (genetics)","level":3,"score":0.33649998903274536},{"id":"https://openalex.org/C18431079","wikidata":"https://www.wikidata.org/wiki/Q1502169","display_name":"Gene expression profiling","level":4,"score":0.2969000041484833},{"id":"https://openalex.org/C150194340","wikidata":"https://www.wikidata.org/wiki/Q26972","display_name":"Gene expression","level":3,"score":0.28940001130104065},{"id":"https://openalex.org/C81941488","wikidata":"https://www.wikidata.org/wiki/Q853421","display_name":"Quantitative trait locus","level":3,"score":0.28600001335144043},{"id":"https://openalex.org/C169822122","wikidata":"https://www.wikidata.org/wiki/Q230187","display_name":"Crosstalk","level":2,"score":0.2815000116825104},{"id":"https://openalex.org/C7952369","wikidata":"https://www.wikidata.org/wiki/Q844116","display_name":"Phenome","level":4,"score":0.262800008058548},{"id":"https://openalex.org/C2796436","wikidata":"https://www.wikidata.org/wiki/Q3109064","display_name":"Gene knockin","level":3,"score":0.2597000002861023}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.11.04.764243","doi":"https://doi.org/10.64898/2026.11.04.764243","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.04.764243","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/11/05/2026.11.04.764243.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.11.04.764243","doi":"https://doi.org/10.64898/2026.11.04.764243","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.04.764243","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/11/05/2026.11.04.764243.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.9391000270843506,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G2094173460","display_name":"The Mary Lyon Centre, the national MRC facility for mouse genetics","funder_award_id":"MC_UP_2201/1","funder_id":"https://openalex.org/F4320334626","funder_display_name":"Medical Research Council"},{"id":"https://openalex.org/G5925143904","display_name":"Mendelian Randomisation","funder_award_id":"MC_UU_00032/1","funder_id":"https://openalex.org/F4320334626","funder_display_name":"Medical Research Council"},{"id":"https://openalex.org/G8383967617","display_name":null,"funder_award_id":"MC_UU_00032","funder_id":"https://openalex.org/F4320320360","funder_display_name":"University of Bristol"}],"funders":[{"id":"https://openalex.org/F4320312060","display_name":"Francis Crick Institute","ror":"https://ror.org/04tnbqb63"},{"id":"https://openalex.org/F4320320360","display_name":"University of Bristol","ror":"https://ror.org/0524sp257"},{"id":"https://openalex.org/F4320334626","display_name":"Medical Research Council","ror":"https://ror.org/03x94j517"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7225327735.pdf","grobid_xml":"https://content.openalex.org/works/W7225327735.grobid-xml"},"referenced_works_count":40,"referenced_works":["https://openalex.org/W1490681631","https://openalex.org/W2048024098","https://openalex.org/W2055729264","https://openalex.org/W2106036991","https://openalex.org/W2118822739","https://openalex.org/W2151464048","https://openalex.org/W2155259933","https://openalex.org/W2157079123","https://openalex.org/W2590714162","https://openalex.org/W2762475241","https://openalex.org/W2783611475","https://openalex.org/W2793634050","https://openalex.org/W2796464660","https://openalex.org/W2895486342","https://openalex.org/W2911274412","https://openalex.org/W2951605527","https://openalex.org/W2963955749","https://openalex.org/W2979820532","https://openalex.org/W3029351535","https://openalex.org/W3108679240","https://openalex.org/W3161425918","https://openalex.org/W3162800482","https://openalex.org/W3207912190","https://openalex.org/W4239641275","https://openalex.org/W4306842054","https://openalex.org/W4307468105","https://openalex.org/W4328049539","https://openalex.org/W4376136225","https://openalex.org/W4386099973","https://openalex.org/W4386171078","https://openalex.org/W4390696774","https://openalex.org/W4394892101","https://openalex.org/W4401575289","https://openalex.org/W4404719328","https://openalex.org/W4408187354","https://openalex.org/W4411317450","https://openalex.org/W4413020599","https://openalex.org/W4417291743","https://openalex.org/W7135246602","https://openalex.org/W7160510064"],"related_works":["https://openalex.org/W2033485847","https://openalex.org/W1995363983","https://openalex.org/W4399752820","https://openalex.org/W2944190934","https://openalex.org/W2911274412","https://openalex.org/W4414338175","https://openalex.org/W2154140021","https://openalex.org/W4251540170","https://openalex.org/W1966552082","https://openalex.org/W2093523947"],"abstract_inverted_index":{"Abstract":[0],"Mouse":[1,81],"gene":[2,12,38,74,208],"knockout":[3],"studies":[4],"are":[5],"a":[6,242],"valuable":[7],"resource":[8],"for":[9,97,114,138,232,241],"understanding":[10,233],"human":[11,30,52,67,234,264],"function":[13],"and":[14,29,127,144,185,202,237,252],"the":[15,42,50,61,78,89,93,149,152,195,239,255,260],"mechanisms":[16],"underlying":[17],"disease.":[18],"However,":[19,194],"translating":[20],"insights":[21],"to":[22,66,103,167,227,254,258],"humans":[23,186],"requires":[24],"causal":[25],"similarities":[26],"between":[27,183],"mouse":[28,33,43,64,73,116,164,256],"phenotypes.":[31,131],"A":[32],"model":[34,246],"is":[35],"transportable":[36],"if":[37],"perturbations":[39,209,253],"that":[40],"impact":[41],"phenotype":[44,53,107],"also":[45,157],"affect":[46],"(in":[47],"orthologous":[48],"genes)":[49],"corresponding":[51],"of":[54,63,112,151,161,163,197,244,263],"interest,":[55],"with":[56,84,206],"consistent":[57],"directionality.":[58],"To":[59],"assess":[60],"transportability":[62,113,162],"models":[65,231],"complex":[68],"traits":[69],"we":[70,109],"combined":[71],"laboratory":[72],"perturbation":[75,173,222],"data":[76,87,223],"from":[77,88],"high-throughput":[79],"International":[80],"Phenotyping":[82],"Consortium":[83],"predicted":[85],"loss-of-function":[86],"UK":[90],"Biobank":[91],"within":[92],"Gene":[94],"Perturbation":[95],"Analysis":[96],"Transportability":[98],"(GPAT)":[99],"framework.":[100],"Applying":[101],"GPAT":[102,188],"30":[104],"matched":[105,176],"mouse-human":[106],"pairs,":[108],"found":[110,158],"evidence":[111,137,160],"12":[115],"phenotypes":[117,177,205],"including":[118],"biochemical":[119],"(e.g.":[120,124,129],"total":[121],"cholesterol),":[122],"cellular":[123],"lymphocyte":[125],"counts)":[126],"anthropometric":[128],"length/height)":[130],"In":[132],"contrast,":[133],"there":[134],"was":[135,199],"limited":[136],"others":[139],"such":[140],"as":[141],"fat":[142],"mass":[143,146],"body":[145],"index":[147],"in":[148,170,212,215],"context":[150],"murine":[153],"experimental":[154,230],"conditions.":[155],"We":[156],"some":[159,207],"glucose":[165],"measurements":[166],"diabetes":[168],"mellitus":[169],"humans.":[171],"Genome-wide":[172],"effects":[174],"on":[175,179],"were":[178],"average":[180],"positively":[181],"correlated":[182],"mice":[184],"(meta-analysis":[187],"P":[189],"=":[190],"2.3x10":[191],"-27":[192],").":[193],"degree":[196],"correlation":[198],"generally":[200],"modest":[201],"heterogeneous":[203],"across":[204],"strongly":[210],"associated":[211],"both":[213],"species":[214],"opposite":[216],"directions.":[217],"Our":[218],"framework":[219],"illustrates":[220],"how":[221],"can":[224],"be":[225],"used":[226],"quantitatively":[228],"validate":[229],"disease":[235],"aetiology":[236],"highlights":[238],"need":[240],"range":[243],"orthogonal":[245],"systems,":[247],"which":[248],"may":[249],"include":[250],"challenges":[251],"knockouts,":[257],"interrogate":[259],"mechanistic":[261],"basis":[262],"genetic":[265],"associations.":[266]},"counts_by_year":[],"updated_date":"2026-11-11T12:16:26.678958","created_date":"2026-11-06T00:00:00"}
