{"id":"https://openalex.org/W2050063758","doi":"https://doi.org/10.1073/pnas.0709868104","title":"A forest-based approach to identifying gene and gene\u2013gene interactions","display_name":"A forest-based approach to identifying gene and gene\u2013gene interactions","publication_year":2007,"publication_date":"2007-11-28","ids":{"openalex":"https://openalex.org/W2050063758","doi":"https://doi.org/10.1073/pnas.0709868104","mag":"2050063758","pmid":"https://pubmed.ncbi.nlm.nih.gov/18048322","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/2148267"},"language":"en","primary_location":{"id":"doi:10.1073/pnas.0709868104","doi":"https://doi.org/10.1073/pnas.0709868104","is_oa":true,"landing_page_url":"https://doi.org/10.1073/pnas.0709868104","pdf_url":"https://www.pnas.org/doi/pdf/10.1073/pnas.0709868104","source":{"id":"https://openalex.org/S125754415","display_name":"Proceedings of the National Academy of Sciences","issn_l":"0027-8424","issn":["0027-8424","1091-6490"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","erih-plus","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320052","host_organization_name":"National Academy of Sciences","host_organization_lineage":["https://openalex.org/P4310320052"],"host_organization_lineage_names":["National Academy of Sciences"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proceedings of the National Academy of Sciences","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":true,"oa_status":"bronze","oa_url":"https://www.pnas.org/doi/pdf/10.1073/pnas.0709868104","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5100441917","display_name":"Xiang 'Anthony' Chen","orcid":"https://orcid.org/0000-0002-2499-8261","observed_orcids":["https://orcid.org/0000-0002-2499-8261"]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Xiang Chen","raw_affiliation_strings":["*Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520-8034; and"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"*Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520-8034; and","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5082644230","display_name":"Ching\u2010Ti Liu","orcid":"https://orcid.org/0000-0002-0703-0742","observed_orcids":["https://orcid.org/0000-0002-0703-0742","https://orcid.org/0000-0001-5957-4197"]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ching-Ti Liu","raw_affiliation_strings":["*Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520-8034; and"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"*Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520-8034; and","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5038086646","display_name":"Meizhuo Zhang","orcid":"https://orcid.org/0009-0003-1827-232X","observed_orcids":["https://orcid.org/0009-0003-1827-232X"]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Meizhuo Zhang","raw_affiliation_strings":["*Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520-8034; and"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"*Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520-8034; and","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5100775543","display_name":"Heping Zhang","orcid":"https://orcid.org/0000-0002-0688-4076","observed_orcids":["https://orcid.org/0000-0002-0688-4076","https://orcid.org/0000-0003-3608-2549"]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]},{"id":"https://openalex.org/I53592917","display_name":"Jiangxi Normal University","ror":"https://ror.org/05nkgk822","country_code":"CN","type":"education","lineage":["https://openalex.org/I53592917"]}],"countries":["CN","US"],"is_corresponding":true,"raw_author_name":"Heping Zhang","raw_affiliation_strings":["*Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520-8034; and","Jiangxi Normal University, Jiangxi 330027, China"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"*Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT 06520-8034; and","institution_ids":["https://openalex.org/I32971472"]},{"raw_affiliation_string":"Jiangxi Normal University, Jiangxi 330027, China","institution_ids":["https://openalex.org/I53592917"]}]}],"institutions":[],"countries_distinct_count":2,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5100775543"],"corresponding_institution_ids":["https://openalex.org/I32971472","https://openalex.org/I53592917"],"apc_list":null,"apc_paid":null,"fwci":4.8165,"has_fulltext":false,"cited_by_count":110,"citation_normalized_percentile":{"value":0.96375957,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":88,"max":99},"biblio":{"volume":"104","issue":"49","first_page":"19199","last_page":"19203"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10261","display_name":"Genetic Associations and Epidemiology","score":0.9829000234603882,"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"}},"topics":[{"id":"https://openalex.org/T10261","display_name":"Genetic Associations and Epidemiology","score":0.9829000234603882,"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/T11468","display_name":"Genetic Mapping and Diversity in Plants and Animals","score":0.003000000026077032,"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/T10751","display_name":"Forensic and Genetic Research","score":0.0020000000949949026,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/gene-gene-interaction","display_name":"gene-gene interaction","score":0.890999972820282},{"id":"https://openalex.org/keywords/gene-environment-interaction","display_name":"gene-environment interaction","score":0.9470000267028809},{"id":"https://openalex.org/keywords/random-forest","display_name":"random forest","score":0.6389999985694885},{"id":"https://openalex.org/keywords/feature-importance","display_name":"feature importance","score":0.9919999837875366},{"id":"https://openalex.org/keywords/age-related-macular-degeneration","display_name":"age-related macular degeneration","score":0.9309999942779541},{"id":"https://openalex.org/keywords/haplotype-identification","display_name":"haplotype identification","score":0.7099999785423279},{"id":"https://openalex.org/keywords/single-nucleotide-polymorphisms","display_name":"single nucleotide polymorphisms","score":0.9850000143051147},{"id":"https://openalex.org/keywords/genetic-association","display_name":"genetic association","score":0.5540000200271606},{"id":"https://openalex.org/keywords/complex-diseases","display_name":"complex diseases","score":0.6399999856948853}],"concepts":[{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.7044874429702759},{"id":"https://openalex.org/C153209595","wikidata":"https://www.wikidata.org/wiki/Q501128","display_name":"Single-nucleotide polymorphism","level":4,"score":0.6432012319564819},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.6382409930229187},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.60780930519104},{"id":"https://openalex.org/C197754878","wikidata":"https://www.wikidata.org/wiki/Q80711","display_name":"Haplotype","level":4,"score":0.591505229473114},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5498577952384949},{"id":"https://openalex.org/C139275648","wikidata":"https://www.wikidata.org/wiki/Q17134011","display_name":"SNP","level":5,"score":0.4364353120326996},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.3248692750930786},{"id":"https://openalex.org/C180754005","wikidata":"https://www.wikidata.org/wiki/Q80726","display_name":"Allele","level":3,"score":0.1285858154296875},{"id":"https://openalex.org/C135763542","wikidata":"https://www.wikidata.org/wiki/Q106016","display_name":"Genotype","level":3,"score":0.12761002779006958}],"mesh":[{"descriptor_ui":"D003198","descriptor_name":"Computer Simulation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D003627","descriptor_name":"Data Interpretation, Statistical","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004777","descriptor_name":"Environment","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004843","descriptor_name":"Epistasis, Genetic","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D006239","descriptor_name":"Haplotypes","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008040","descriptor_name":"Genetic Linkage","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D008268","descriptor_name":"Macular Degeneration","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":false},{"descriptor_ui":"D008957","descriptor_name":"Models, Genetic","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D020022","descriptor_name":"Genetic Predisposition to Disease","qualifier_ui":"Q000235","qualifier_name":"genetics","is_major_topic":true},{"descriptor_ui":"D020641","descriptor_name":"Polymorphism, Single Nucleotide","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":3,"locations":[{"id":"doi:10.1073/pnas.0709868104","doi":"https://doi.org/10.1073/pnas.0709868104","is_oa":true,"landing_page_url":"https://doi.org/10.1073/pnas.0709868104","pdf_url":"https://www.pnas.org/doi/pdf/10.1073/pnas.0709868104","source":{"id":"https://openalex.org/S125754415","display_name":"Proceedings of the National Academy of Sciences","issn_l":"0027-8424","issn":["0027-8424","1091-6490"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","erih-plus","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320052","host_organization_name":"National Academy of Sciences","host_organization_lineage":["https://openalex.org/P4310320052"],"host_organization_lineage_names":["National Academy of Sciences"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proceedings of the National Academy of Sciences","raw_type":"journal-article"},{"id":"pmh:oai:pubmedcentral.nih.gov:2148267","doi":null,"is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/2148267","pdf_url":null,"source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proc Natl Acad Sci U S A","raw_type":"Text"},{"id":"pmid:18048322","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/18048322","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proceedings of the National Academy of Sciences of the United States of America","raw_type":"Journal Article"}],"best_oa_location":{"id":"doi:10.1073/pnas.0709868104","doi":"https://doi.org/10.1073/pnas.0709868104","is_oa":true,"landing_page_url":"https://doi.org/10.1073/pnas.0709868104","pdf_url":"https://www.pnas.org/doi/pdf/10.1073/pnas.0709868104","source":{"id":"https://openalex.org/S125754415","display_name":"Proceedings of the National Academy of Sciences","issn_l":"0027-8424","issn":["0027-8424","1091-6490"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-class-a","anvur-scientific","cwts-core","dongbi-a","doyens","erih-plus","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320052","host_organization_name":"National Academy of Sciences","host_organization_lineage":["https://openalex.org/P4310320052"],"host_organization_lineage_names":["National Academy of Sciences"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Proceedings of the National Academy of Sciences","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.8371999859809875,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G2991635374","display_name":"Methodological Research on Substance Use","funder_award_id":"K02DA017713","funder_id":"https://openalex.org/F4320337347","funder_display_name":"National Institute on Drug Abuse"},{"id":"https://openalex.org/G358258836","display_name":"Data Management, Statistics, and informatics Core","funder_award_id":"U01HD050062","funder_id":"https://openalex.org/F4320337611","funder_display_name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development"},{"id":"https://openalex.org/G8471955614","display_name":"Analysis of Genomic Data for Complex Traits","funder_award_id":"R01DA016750","funder_id":"https://openalex.org/F4320337347","funder_display_name":"National Institute on Drug Abuse"}],"funders":[{"id":"https://openalex.org/F4320337347","display_name":"National Institute on Drug Abuse","ror":"https://ror.org/00fq5cm18"},{"id":"https://openalex.org/F4320337611","display_name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","ror":"https://ror.org/04byxyr05"}],"has_content":{"pdf":true,"grobid_xml":false},"content_urls":{"pdf":"https://content.openalex.org/works/W2050063758.pdf"},"referenced_works_count":41,"referenced_works":["https://openalex.org/W181437532","https://openalex.org/W1508985588","https://openalex.org/W1542772707","https://openalex.org/W1553500812","https://openalex.org/W1581351010","https://openalex.org/W1594031697","https://openalex.org/W1745222097","https://openalex.org/W1927664716","https://openalex.org/W1964901903","https://openalex.org/W1980175560","https://openalex.org/W1981714996","https://openalex.org/W1981723690","https://openalex.org/W1990390726","https://openalex.org/W1993244518","https://openalex.org/W1996509864","https://openalex.org/W1999730441","https://openalex.org/W2020430676","https://openalex.org/W2021051417","https://openalex.org/W2042413629","https://openalex.org/W2052182252","https://openalex.org/W2058880763","https://openalex.org/W2064539914","https://openalex.org/W2067523962","https://openalex.org/W2076290011","https://openalex.org/W2086099578","https://openalex.org/W2105306382","https://openalex.org/W2106901733","https://openalex.org/W2113784410","https://openalex.org/W2117386992","https://openalex.org/W2118921994","https://openalex.org/W2119716615","https://openalex.org/W2124718950","https://openalex.org/W2138171990","https://openalex.org/W2158411188","https://openalex.org/W2159267146","https://openalex.org/W2160429819","https://openalex.org/W2168894308","https://openalex.org/W2330820318","https://openalex.org/W2911964244","https://openalex.org/W3085162807","https://openalex.org/W3145351529"],"related_works":["https://openalex.org/W2025681012","https://openalex.org/W2134874218","https://openalex.org/W2413696386","https://openalex.org/W2323380786","https://openalex.org/W2319197375","https://openalex.org/W2008719690","https://openalex.org/W2101350555","https://openalex.org/W2122477058","https://openalex.org/W2317095450","https://openalex.org/W2062437660"],"abstract_inverted_index":{"Multiple":[0],"genes,":[1],"gene-by-gene":[2],"interactions,":[3],"and":[4,41,53,70,85,176,183,186],"gene-by-environment":[5],"interactions":[6,16,185],"are":[7,17,153],"believed":[8],"to":[9,19,38,179],"underlie":[10],"most":[11],"complex":[12,32],"diseases.":[13],"However,":[14],"such":[15],"difficult":[18,37],"identify.":[20],"Although":[21],"there":[22],"have":[23],"been":[24],"recent":[25],"successes":[26],"in":[27],"identifying":[28],"genetic":[29,91,118],"variants":[30],"for":[31,67,77,124,158,192],"diseases,":[33],"it":[34,172],"still":[35],"remains":[36],"identify":[39,180],"gene-gene":[40],"gene-environment":[42],"interactions.":[43],"To":[44],"overcome":[45],"this":[46,168],"difficulty,":[47],"we":[48],"propose":[49],"a":[50,54,73,104,116,159,174,188],"forest-based":[51],"approach":[52,61],"concept":[55],"of":[56,81,96,103,162,167],"variable":[57],"importance.":[58],"The":[59],"proposed":[60],"is":[62,170],"demonstrated":[63],"by":[64,72],"simulation":[65],"study":[66],"its":[68,78],"validity":[69],"illustrated":[71],"real":[74,83],"data":[75,84,87,106],"analysis":[76,102],"use.":[79],"Analyses":[80],"both":[82],"simulated":[86],"based":[88],"on":[89,108,137],"published":[90,105],"models":[92],"show":[93],"the":[94,156,165],"effectiveness":[95],"our":[97,101],"approach.":[98],"For":[99],"example,":[100],"set":[107],"age-related":[109],"macular":[110],"degeneration":[111],"(AMD)":[112],"not":[113],"only":[114],"confirmed":[115],"known":[117],"variant":[119,191],"(P":[120,146],"value":[121,147],"=":[122,148],"2E-6)":[123],"AMD,":[125],"but":[126],"also":[127],"revealed":[128],"an":[129],"unreported":[130],"haplotype":[131],"surrounding":[132],"single-nucleotide":[133],"polymorphism":[134],"(SNP)":[135],"rs10272438":[136],"chromosome":[138],"7":[139],"that":[140],"was":[141],"significantly":[142],"associated":[143],"with":[144],"AMD":[145],"0.0024).":[149],"These":[150],"significance":[151],"levels":[152],"obtained":[154],"after":[155],"consideration":[157],"large":[160],"number":[161],"SNPs.":[163],"Thus,":[164],"importance":[166],"work":[169],"twofold:":[171],"proposes":[173],"powerful":[175],"flexible":[177],"method":[178],"high-risk":[181],"haplotypes":[182],"their":[184],"reveals":[187],"potentially":[189],"protective":[190],"AMD.":[193]},"counts_by_year":[{"year":2024,"cited_by_count":4},{"year":2023,"cited_by_count":1},{"year":2022,"cited_by_count":5},{"year":2021,"cited_by_count":6},{"year":2020,"cited_by_count":7},{"year":2019,"cited_by_count":3},{"year":2018,"cited_by_count":4},{"year":2017,"cited_by_count":1},{"year":2016,"cited_by_count":4},{"year":2015,"cited_by_count":3},{"year":2014,"cited_by_count":7},{"year":2013,"cited_by_count":7},{"year":2012,"cited_by_count":11}],"updated_date":"2026-11-06T12:05:46.655746","created_date":"2016-06-24T00:00:00"}
