{"id":"https://openalex.org/W7225273248","doi":"https://doi.org/10.64898/2026.11.03.762814","title":"SeverYX: An ensemble framework for robust variant severity classification","display_name":"SeverYX: An ensemble framework for robust variant severity classification","publication_year":2026,"publication_date":"2026-11-04","ids":{"openalex":"https://openalex.org/W7225273248","doi":"https://doi.org/10.64898/2026.11.03.762814"},"language":"en","primary_location":{"id":"doi:10.64898/2026.11.03.762814","doi":"https://doi.org/10.64898/2026.11.03.762814","is_oa":false,"landing_page_url":"https://doi.org/10.64898/2026.11.03.762814","pdf_url":null,"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":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5112946766","display_name":"Evyatar Mor","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210121829","display_name":"Genex Systems (United States)","ror":"https://ror.org/02mz0pc52","country_code":"US","type":"company","lineage":["https://openalex.org/I4210121829"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Evyatar Mor","raw_affiliation_strings":["Geneyx Genomex LTD"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Geneyx Genomex LTD","institution_ids":["https://openalex.org/I4210121829"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5160641610","display_name":"Eldar Dedic","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210121829","display_name":"Genex Systems (United States)","ror":"https://ror.org/02mz0pc52","country_code":"US","type":"company","lineage":["https://openalex.org/I4210121829"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Eldar Dedic","raw_affiliation_strings":["Geneyx Genomex LTD"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Geneyx Genomex LTD","institution_ids":["https://openalex.org/I4210121829"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5070135708","display_name":"Yaron Mazor","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I4210121829","display_name":"Genex Systems (United States)","ror":"https://ror.org/02mz0pc52","country_code":"US","type":"company","lineage":["https://openalex.org/I4210121829"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Yaron Mazor","raw_affiliation_strings":["Geneyx Genomex LTD"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Geneyx Genomex LTD","institution_ids":["https://openalex.org/I4210121829"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5090916718","display_name":"Suzanne Drury","orcid":"https://orcid.org/0000-0001-7915-6072","observed_orcids":["https://orcid.org/0000-0001-7915-6072"]},"institutions":[{"id":"https://openalex.org/I4210121829","display_name":"Genex Systems (United States)","ror":"https://ror.org/02mz0pc52","country_code":"US","type":"company","lineage":["https://openalex.org/I4210121829"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Suzanne Drury","raw_affiliation_strings":["Geneyx Genomex LTD"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Geneyx Genomex LTD","institution_ids":["https://openalex.org/I4210121829"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5086624955","display_name":"Hagar Mor\u2010Shaked","orcid":"https://orcid.org/0000-0001-6631-0376","observed_orcids":["https://orcid.org/0000-0001-6631-0376"]},"institutions":[{"id":"https://openalex.org/I4210121829","display_name":"Genex Systems (United States)","ror":"https://ror.org/02mz0pc52","country_code":"US","type":"company","lineage":["https://openalex.org/I4210121829"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Hagar Mor-Shaked","raw_affiliation_strings":["Geneyx Genomex LTD"],"raw_orcid":"https://orcid.org/0000-0001-6631-0376","affiliations":[{"raw_affiliation_string":"Geneyx Genomex LTD","institution_ids":["https://openalex.org/I4210121829"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5072606404","display_name":"Lina Zelinger","orcid":"https://orcid.org/0000-0003-3028-7172","observed_orcids":["https://orcid.org/0000-0003-3028-7172"]},"institutions":[{"id":"https://openalex.org/I4210121829","display_name":"Genex Systems (United States)","ror":"https://ror.org/02mz0pc52","country_code":"US","type":"company","lineage":["https://openalex.org/I4210121829"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Lina Zelinger","raw_affiliation_strings":["Geneyx Genomex LTD"],"raw_orcid":"https://orcid.org/0000-0003-3028-7172","affiliations":[{"raw_affiliation_string":"Geneyx Genomex LTD","institution_ids":["https://openalex.org/I4210121829"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I4210121829"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"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/T11642","display_name":"Genomics and Rare Diseases","score":1.0,"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/T11642","display_name":"Genomics and Rare Diseases","score":1.0,"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/T10015","display_name":"Genomics and Phylogenetic Studies","score":0.0,"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":0.0,"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":[],"concepts":[{"id":"https://openalex.org/C160798450","wikidata":"https://www.wikidata.org/wiki/Q4230870","display_name":"Concordance","level":2,"score":0.858299970626831},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.46560001373291016},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.4287000000476837},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.4260999858379364},{"id":"https://openalex.org/C167085575","wikidata":"https://www.wikidata.org/wiki/Q6803654","display_name":"Mean squared prediction error","level":2,"score":0.42340001463890076},{"id":"https://openalex.org/C117220453","wikidata":"https://www.wikidata.org/wiki/Q5172842","display_name":"Correlation","level":2,"score":0.41780000925064087},{"id":"https://openalex.org/C75563809","wikidata":"https://www.wikidata.org/wiki/Q2656896","display_name":"Missense mutation","level":4,"score":0.3968000113964081},{"id":"https://openalex.org/C527412718","wikidata":"https://www.wikidata.org/wiki/Q855395","display_name":"Interpretation (philosophy)","level":2,"score":0.39590001106262207},{"id":"https://openalex.org/C124101348","wikidata":"https://www.wikidata.org/wiki/Q172491","display_name":"Data mining","level":1,"score":0.37950000166893005},{"id":"https://openalex.org/C119857082","wikidata":"https://www.wikidata.org/wiki/Q2539","display_name":"Machine learning","level":1,"score":0.3718999922275543},{"id":"https://openalex.org/C189206191","wikidata":"https://www.wikidata.org/wiki/Q222046","display_name":"Genomics","level":4,"score":0.36800000071525574},{"id":"https://openalex.org/C48044578","wikidata":"https://www.wikidata.org/wiki/Q727490","display_name":"Scalability","level":2,"score":0.3677000105381012},{"id":"https://openalex.org/C2993807623","wikidata":"https://www.wikidata.org/wiki/Q7020","display_name":"Genetic data","level":3,"score":0.33090001344680786},{"id":"https://openalex.org/C164085508","wikidata":"https://www.wikidata.org/wiki/Q4811327","display_name":"Matthews correlation coefficient","level":3,"score":0.3197999894618988},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.2996000051498413},{"id":"https://openalex.org/C2781059462","wikidata":"https://www.wikidata.org/wiki/Q5158906","display_name":"Concordance correlation coefficient","level":2,"score":0.2946000099182129},{"id":"https://openalex.org/C2777735758","wikidata":"https://www.wikidata.org/wiki/Q817765","display_name":"Path (computing)","level":2,"score":0.29109999537467957},{"id":"https://openalex.org/C21200559","wikidata":"https://www.wikidata.org/wiki/Q7451068","display_name":"Sensitivity (control systems)","level":2,"score":0.28859999775886536},{"id":"https://openalex.org/C2779974597","wikidata":"https://www.wikidata.org/wiki/Q28448986","display_name":"Clinical Practice","level":2,"score":0.2874999940395355},{"id":"https://openalex.org/C3020132585","wikidata":"https://www.wikidata.org/wiki/Q2671652","display_name":"Diagnostic accuracy","level":2,"score":0.2847000062465668},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.2822999954223633},{"id":"https://openalex.org/C2989179672","wikidata":"https://www.wikidata.org/wiki/Q6806500","display_name":"Clinical decision making","level":2,"score":0.28220000863075256},{"id":"https://openalex.org/C45804977","wikidata":"https://www.wikidata.org/wiki/Q7239673","display_name":"Predictive modelling","level":2,"score":0.2808000147342682},{"id":"https://openalex.org/C2993967602","wikidata":"https://www.wikidata.org/wiki/Q5532932","display_name":"Genetic variants","level":4,"score":0.2615000009536743},{"id":"https://openalex.org/C2776401178","wikidata":"https://www.wikidata.org/wiki/Q12050496","display_name":"Feature (linguistics)","level":2,"score":0.2574000060558319},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.25540000200271606},{"id":"https://openalex.org/C33923547","wikidata":"https://www.wikidata.org/wiki/Q395","display_name":"Mathematics","level":0,"score":0.2535000145435333},{"id":"https://openalex.org/C84839998","wikidata":"https://www.wikidata.org/wiki/Q5249245","display_name":"Decision rule","level":2,"score":0.25290000438690186}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.11.03.762814","doi":"https://doi.org/10.64898/2026.11.03.762814","is_oa":false,"landing_page_url":"https://doi.org/10.64898/2026.11.03.762814","pdf_url":null,"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":null,"license_id":null,"version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":null,"sustainable_development_goals":[],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":[],"abstract_inverted_index":{"Accurate":[0],"interpretation":[1,199],"of":[2,57,89,93,127,149],"genetic":[3],"variants":[4,60,95,104],"in":[5,116],"clinical":[6],"genomics":[7],"depends":[8],"on":[9],"reconciling":[10],"multiple":[11],"computational":[12],"predictors":[13,35],"that":[14,29,169],"often":[15],"disagree":[16],"or":[17],"provide":[18],"incomplete":[19],"evidence.":[20],"We":[21,49],"present":[22],"SeverYX,":[23],"a":[24,37,53,84,147,172,189],"transparent,":[25,173],"rule-based":[26],"ensemble":[27],"framework":[28],"consolidates":[30],"conservation,":[31],"splicing,":[32],"and":[33,73,91,105,109,129,156,175,188],"functional-impact":[34],"into":[36,183,197],"three-tier":[38],"severity":[39,186],"classification":[40],"(\u2032High\u2032,":[41],"\u2032Medium\u2032,":[42],"\u2032Low\u2032)":[43],"through":[44],"an":[45],"effect-aware":[46],"decision":[47],"architecture.":[48],"benchmarked":[50],"SeverYX":[51,170],"against":[52],"curated":[54],"ClinVar":[55],"dataset":[56],"270,208":[58],"MANE-transcript":[59],"(86,161":[61],"pathogenic/likely":[62],"pathogenic,":[63],"184,047":[64],"benign/likely":[65],"benign),":[66],"stratified":[67],"by":[68],"molecular":[69],"consequence,":[70],"review":[71],"status,":[72],"haploinsufficiency.":[74],"The":[75],"baseline":[76],"configuration":[77],"achieved":[78],"97.6%":[79],"concordance":[80,136],"with":[81,124],"ClinVar;":[82],"at":[83],"fixed":[85],"High":[86,142,151],"cut,":[87],"90.0%":[88],"pathogenic":[90,111,150],"2.0%":[92],"benign":[94,141],"were":[96],"assigned":[97],"High.":[98],"Concordance":[99],"was":[100],"highest":[101],"for":[102,107,178,192],"loss-of-function":[103],"lowest":[106],"non-coding":[108],"unclassified":[110],"variants,":[112],"reflecting":[113],"known":[114],"gaps":[115],"current":[117],"predictive":[118,195],"tools.":[119],"Systematic":[120],"threshold":[121],"optimization,":[122],"combined":[123],"the":[125,140,158],"addition":[126],"AlphaMissense":[128],"REVEL":[130],"as":[131],"missense":[132],"predictors,":[133],"raised":[134],"overall":[135],"to":[137,144,154,164],"98.7%,":[138],"reduced":[139],"rate":[143],"0.4%":[145],"(at":[146],"cost":[148],"sensitivity":[152],"falling":[153],"88.3%),":[155],"improved":[157],"Matthews":[159],"correlation":[160],"coefficient":[161],"from":[162],"0.895":[163],"0.908.":[165],"These":[166],"results":[167],"show":[168],"offers":[171],"reproducible":[174],"extensible":[176],"approach":[177],"consolidating":[179],"heterogeneous":[180],"variant-effect":[181],"evidence":[182],"clinically":[184],"interpretable":[185],"calls,":[187],"scalable":[190],"path":[191],"incorporating":[193],"future":[194],"models":[196],"genomic":[198],"workflows.":[200]},"counts_by_year":[],"updated_date":"2026-11-05T12:25:35.769452","created_date":"2026-11-05T00:00:00"}
