{"id":"https://openalex.org/W3137311299","doi":"https://doi.org/10.1186/s12859-021-03982-3","title":"Nonlinear ridge regression improves cell-type-specific differential expression analysis","display_name":"Nonlinear ridge regression improves cell-type-specific differential expression analysis","publication_year":2021,"publication_date":"2021-03-22","ids":{"openalex":"https://openalex.org/W3137311299","doi":"https://doi.org/10.1186/s12859-021-03982-3","mag":"3137311299","pmid":"https://pubmed.ncbi.nlm.nih.gov/33752591"},"language":"en","primary_location":{"id":"doi:10.1186/s12859-021-03982-3","is_oa":true,"landing_page_url":"https://doi.org/10.1186/s12859-021-03982-3","pdf_url":"https://bmcbioinformatics.biomedcentral.com/counter/pdf/10.1186/s12859-021-03982-3","source":{"id":"https://openalex.org/S19032547","display_name":"BMC Bioinformatics","issn_l":"1471-2105","issn":["1471-2105"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310320256","host_organization_name":"BioMed Central","host_organization_lineage":["https://openalex.org/P4310320256","https://openalex.org/P4310319965"],"host_organization_lineage_names":["BioMed Central","Springer Nature"],"type":"journal"},"license":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"BMC Bioinformatics","raw_type":"journal-article"},"type":"article","indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://bmcbioinformatics.biomedcentral.com/counter/pdf/10.1186/s12859-021-03982-3","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5066325623","display_name":"Fumihiko Takeuchi","orcid":"https://orcid.org/0000-0003-3185-5661"},"institutions":[{"id":"https://openalex.org/I4210094012","display_name":"National Center for Global Health and Medicine","ror":"https://ror.org/00r9w3j27","country_code":"JP","type":"healthcare","lineage":["https://openalex.org/I4210094012"]}],"countries":["JP"],"is_corresponding":true,"raw_author_name":"Fumihiko Takeuchi","raw_affiliation_strings":["Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine (NCGM), 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan. fumihiko@takeuchi.name","Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine (NCGM), 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan"],"raw_orcid":"https://orcid.org/0000-0003-3185-5661","affiliations":[{"raw_affiliation_string":"Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine (NCGM), 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan. fumihiko@takeuchi.name","institution_ids":["https://openalex.org/I4210094012"]},{"raw_affiliation_string":"Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine (NCGM), 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan","institution_ids":["https://openalex.org/I4210094012"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5040049943","display_name":"Norihiro Kato","orcid":"https://orcid.org/0000-0002-2433-8415"},"institutions":[{"id":"https://openalex.org/I4210094012","display_name":"National Center for Global Health and Medicine","ror":"https://ror.org/00r9w3j27","country_code":"JP","type":"healthcare","lineage":["https://openalex.org/I4210094012"]}],"countries":["JP"],"is_corresponding":false,"raw_author_name":"Norihiro Kato","raw_affiliation_strings":["Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine (NCGM), 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine (NCGM), 1-21-1 Toyama, Shinjuku-ku, Tokyo, 162-8655, Japan","institution_ids":["https://openalex.org/I4210094012"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5066325623"],"corresponding_institution_ids":["https://openalex.org/I4210094012"],"apc_list":{"value":1690,"currency":"GBP","value_usd":2072},"apc_paid":{"value":1690,"currency":"GBP","value_usd":2072},"fwci":0.3256,"has_fulltext":true,"cited_by_count":6,"citation_normalized_percentile":{"value":0.55189282,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":90,"max":98},"biblio":{"volume":"22","issue":"1","first_page":"141","last_page":"141"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10269","display_name":"Epigenetics and DNA Methylation","score":0.1842000037431717,"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/T10269","display_name":"Epigenetics and DNA Methylation","score":0.1842000037431717,"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":0.18400000035762787,"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/T11297","display_name":"Ferroptosis and cancer prognosis","score":0.17990000545978546,"subfield":{"id":"https://openalex.org/subfields/2740","display_name":"Pulmonary and Respiratory Medicine"},"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/multicollinearity","display_name":"Multicollinearity","score":0.8592538833618164},{"id":"https://openalex.org/keywords/linear-regression","display_name":"Linear regression","score":0.5289292931556702},{"id":"https://openalex.org/keywords/regression","display_name":"Regression","score":0.49802374839782715},{"id":"https://openalex.org/keywords/statistics","display_name":"Statistics","score":0.4711873531341553},{"id":"https://openalex.org/keywords/regression-analysis","display_name":"Regression analysis","score":0.44087710976600647},{"id":"https://openalex.org/keywords/computer-science","display_name":"Computer science","score":0.4083007276058197},{"id":"https://openalex.org/keywords/mathematics","display_name":"Mathematics","score":0.3941262662410736},{"id":"https://openalex.org/keywords/biology","display_name":"Biology","score":0.36301949620246887},{"id":"https://openalex.org/keywords/data-mining","display_name":"Data mining","score":0.360198438167572}],"concepts":[{"id":"https://openalex.org/C189285262","wikidata":"https://www.wikidata.org/wiki/Q1332350","display_name":"Multicollinearity","level":3,"score":0.8592538833618164},{"id":"https://openalex.org/C48921125","wikidata":"https://www.wikidata.org/wiki/Q10861030","display_name":"Linear regression","level":2,"score":0.5289292931556702},{"id":"https://openalex.org/C83546350","wikidata":"https://www.wikidata.org/wiki/Q1139051","display_name":"Regression","level":2,"score":0.49802374839782715},{"id":"https://openalex.org/C105795698","wikidata":"https://www.wikidata.org/wiki/Q12483","display_name":"Statistics","level":1,"score":0.4711873531341553},{"id":"https://openalex.org/C152877465","wikidata":"https://www.wikidata.org/wiki/Q208042","display_name":"Regression analysis","level":2,"score":0.44087710976600647},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.4083007276058197},{"id":"https://openalex.org/C33923547","wikidata":"https://www.wikidata.org/wiki/Q395","display_name":"Mathematics","level":0,"score":0.3941262662410736},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.36301949620246887},{"id":"https://openalex.org/C124101348","wikidata":"https://www.wikidata.org/wiki/Q172491","display_name":"Data mining","level":1,"score":0.360198438167572}],"mesh":[{"descriptor_ui":"D000081122","descriptor_name":"Epigenome","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D000081122","descriptor_name":"Epigenome","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D000081122","descriptor_name":"Epigenome","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D000465","descriptor_name":"Algorithms","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000465","descriptor_name":"Algorithms","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000465","descriptor_name":"Algorithms","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D010641","descriptor_name":"Phenotype","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D010641","descriptor_name":"Phenotype","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D010641","descriptor_name":"Phenotype","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D012984","descriptor_name":"Software","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D012984","descriptor_name":"Software","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D012984","descriptor_name":"Software","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D016014","descriptor_name":"Linear Models","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016014","descriptor_name":"Linear Models","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D016014","descriptor_name":"Linear Models","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":4,"locations":[{"id":"doi:10.1186/s12859-021-03982-3","is_oa":true,"landing_page_url":"https://doi.org/10.1186/s12859-021-03982-3","pdf_url":"https://bmcbioinformatics.biomedcentral.com/counter/pdf/10.1186/s12859-021-03982-3","source":{"id":"https://openalex.org/S19032547","display_name":"BMC Bioinformatics","issn_l":"1471-2105","issn":["1471-2105"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310320256","host_organization_name":"BioMed Central","host_organization_lineage":["https://openalex.org/P4310320256","https://openalex.org/P4310319965"],"host_organization_lineage_names":["BioMed Central","Springer Nature"],"type":"journal"},"license":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"BMC Bioinformatics","raw_type":"journal-article"},{"id":"pmid:33752591","is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/33752591","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,"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":"BMC bioinformatics","raw_type":null},{"id":"pmh:oai:doaj.org/article:48a4862920504b23b84464fe07719554","is_oa":true,"landing_page_url":"https://doaj.org/article/48a4862920504b23b84464fe07719554","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by-sa","license_id":"https://openalex.org/licenses/cc-by-sa","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"BMC Bioinformatics, Vol 22, Iss 1, Pp 1-25 (2021)","raw_type":"article"},{"id":"pmh:oai:pubmedcentral.nih.gov:7986289","is_oa":true,"landing_page_url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7986289","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,"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":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"BMC Bioinformatics","raw_type":"Text"}],"best_oa_location":{"id":"doi:10.1186/s12859-021-03982-3","is_oa":true,"landing_page_url":"https://doi.org/10.1186/s12859-021-03982-3","pdf_url":"https://bmcbioinformatics.biomedcentral.com/counter/pdf/10.1186/s12859-021-03982-3","source":{"id":"https://openalex.org/S19032547","display_name":"BMC Bioinformatics","issn_l":"1471-2105","issn":["1471-2105"],"is_oa":true,"is_in_doaj":true,"is_core":true,"host_organization":"https://openalex.org/P4310320256","host_organization_name":"BioMed Central","host_organization_lineage":["https://openalex.org/P4310320256","https://openalex.org/P4310319965"],"host_organization_lineage_names":["BioMed Central","Springer Nature"],"type":"journal"},"license":"other-oa","license_id":"https://openalex.org/licenses/other-oa","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"BMC Bioinformatics","raw_type":"journal-article"},"sustainable_development_goals":[],"awards":[{"id":"https://openalex.org/G4285096929","display_name":null,"funder_award_id":"20A1013","funder_id":"https://openalex.org/F4320313449","funder_display_name":"National Center for Global Health and Medicine"},{"id":"https://openalex.org/G5956586827","display_name":null,"funder_award_id":"19A2004","funder_id":"https://openalex.org/F4320313449","funder_display_name":"National Center for Global Health and Medicine"},{"id":"https://openalex.org/G8952238683","display_name":null,"funder_award_id":"JP16K07218","funder_id":"https://openalex.org/F4320334764","funder_display_name":"Japan Society for the Promotion of Science"}],"funders":[{"id":"https://openalex.org/F4320313449","display_name":"National Center for Global Health and Medicine","ror":"https://ror.org/00r9w3j27"},{"id":"https://openalex.org/F4320334764","display_name":"Japan Society for the Promotion of Science","ror":"https://ror.org/00hhkn466"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W3137311299.pdf","grobid_xml":"https://content.openalex.org/works/W3137311299.grobid-xml"},"referenced_works_count":42,"referenced_works":["https://openalex.org/W1546833668","https://openalex.org/W1986098236","https://openalex.org/W2011988545","https://openalex.org/W2021880506","https://openalex.org/W2028934624","https://openalex.org/W2029033394","https://openalex.org/W2032980774","https://openalex.org/W2046915036","https://openalex.org/W2056040742","https://openalex.org/W2066796151","https://openalex.org/W2080591050","https://openalex.org/W2086088557","https://openalex.org/W2093358653","https://openalex.org/W2093754862","https://openalex.org/W2110248945","https://openalex.org/W2113611401","https://openalex.org/W2129631522","https://openalex.org/W2133743912","https://openalex.org/W2137128340","https://openalex.org/W2145347221","https://openalex.org/W2155388222","https://openalex.org/W2168475916","https://openalex.org/W2169556367","https://openalex.org/W2295126179","https://openalex.org/W2530386703","https://openalex.org/W2587308124","https://openalex.org/W2599524418","https://openalex.org/W2611750352","https://openalex.org/W2761275051","https://openalex.org/W2763780776","https://openalex.org/W2788357641","https://openalex.org/W2795879047","https://openalex.org/W2797247465","https://openalex.org/W2919386822","https://openalex.org/W2938759794","https://openalex.org/W2952420117","https://openalex.org/W2953022051","https://openalex.org/W2953757801","https://openalex.org/W2965166405","https://openalex.org/W3023241526","https://openalex.org/W3034461749","https://openalex.org/W6667299493"],"related_works":["https://openalex.org/W2009886987","https://openalex.org/W3114452526","https://openalex.org/W2268505974","https://openalex.org/W4390687192","https://openalex.org/W875826547","https://openalex.org/W3130447296","https://openalex.org/W1127100678","https://openalex.org/W2101914902","https://openalex.org/W2387884177","https://openalex.org/W2002358553"],"abstract_inverted_index":{"BACKGROUND:":[0],"Epigenome-wide":[1],"association":[2,184],"studies":[3],"(EWAS)":[4],"and":[5,81,90,155,163,166,208],"differential":[6,102,205],"gene":[7,206],"expression":[8,33,207],"analyses":[9],"are":[10,34,65,127],"generally":[11],"performed":[12,182],"on":[13,30,186],"tissue":[14],"samples,":[15],"which":[16,130],"consist":[17],"of":[18,24,35,55],"multiple":[19],"cell":[20,52,78,95],"types.":[21],"Cell-type-specific":[22],"effects":[23,64],"a":[25,56],"trait,":[26],"such":[27],"as":[28],"disease,":[29],"the":[31,49,74,77,82,108,124,139,160,168],"omics":[32,46,188],"interest":[36],"but":[37],"difficult":[38],"or":[39],"costly":[40],"to":[41,133,171],"measure":[42],"experimentally.":[43],"By":[44],"measuring":[45],"data":[47,189],"for":[48,196,202],"bulk":[50,187],"tissue,":[51],"type":[53,79],"composition":[54,96],"sample":[57],"can":[58],"be":[59],"inferred":[60],"statistically.":[61],"Subsequently,":[62],"cell-type-specific":[63,183,203],"estimated":[66],"by":[67],"linear":[68,100],"regression":[69,150,181,201],"that":[70,123],"includes":[71],"terms":[72,126],"representing":[73],"interaction":[75,125],"between":[76],"proportions":[80],"trait.":[83],"This":[84],"approach":[85],"involves":[86],"two":[87,114],"issues,":[88],"scaling":[89],"multicollinearity.":[91],"RESULTS:":[92],"First,":[93],"although":[94],"is":[97,104,131,213],"analyzed":[98,105],"in":[99,107,175],"scale,":[101],"methylation/expression":[103],"suitably":[106],"logit/log":[109],"scale.":[110],"To":[111,136],"simultaneously":[112],"analyze":[113],"scales,":[115],"we":[116,121,141],"applied":[117,142],"nonlinear":[118,148,199],"regression.":[119,135],"Second,":[120],"show":[122],"highly":[128],"collinear,":[129],"obstructive":[132],"ordinary":[134],"cope":[137],"with":[138,190],"multicollinearity,":[140],"ridge":[143,149,180,200],"regularization.":[144],"In":[145],"simulated":[146],"data,":[147],"attained":[151,159],"well-balanced":[152,191],"sensitivity,":[153],"specificity":[154],"precision.":[156],"Marginal":[157],"model":[158],"lowest":[161],"precision":[162],"highest":[164],"sensitivity":[165],"was":[167],"only":[169],"algorithm":[170],"detect":[172],"weak":[173],"signal":[174],"real":[176],"data.":[177],"CONCLUSION:":[178],"Nonlinear":[179],"test":[185],"performance.":[192],"The":[193,211],"omicwas":[194],"package":[195],"R":[197],"implements":[198],"EWAS,":[204],"QTL":[209],"analyses.":[210],"software":[212],"freely":[214],"available":[215],"from":[216],"https://github.com/fumi-github/omicwas.":[217]},"counts_by_year":[{"year":2026,"cited_by_count":1},{"year":2025,"cited_by_count":1},{"year":2022,"cited_by_count":1},{"year":2021,"cited_by_count":3}],"updated_date":"2026-05-21T06:26:12.895304","created_date":"2025-10-10T00:00:00"}
