{"id":"https://openalex.org/W7128914334","doi":"https://doi.org/10.64898/2026.02.12.705543","title":"Feature-based in-silico model to predict the Mycobacterium tuberculosis bedaquiline phenotype associated with Rv0678 variants","display_name":"Feature-based in-silico model to predict the Mycobacterium tuberculosis bedaquiline phenotype associated with Rv0678 variants","publication_year":2026,"publication_date":"2026-02-14","ids":{"openalex":"https://openalex.org/W7128914334","doi":"https://doi.org/10.64898/2026.02.12.705543"},"language":"en","primary_location":{"id":"doi:10.64898/2026.02.12.705543","doi":"https://doi.org/10.64898/2026.02.12.705543","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.02.12.705543","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":"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://doi.org/10.64898/2026.02.12.705543","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5083287284","display_name":"Wilma Ursula Quispe-Rojas","orcid":"https://orcid.org/0000-0002-9174-3947","observed_orcids":["https://orcid.org/0000-0002-9174-3947"]},"institutions":[{"id":"https://openalex.org/I149213910","display_name":"University of Antwerp","ror":"https://ror.org/008x57b05","country_code":"BE","type":"education","lineage":["https://openalex.org/I149213910"]}],"countries":["BE"],"is_corresponding":false,"raw_author_name":"Wilma Quispe Rojas","raw_affiliation_strings":["Department of Family Medicine and Population Health, Global Health Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Family Medicine and Population Health, Global Health Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium","institution_ids":["https://openalex.org/I149213910"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5075707435","display_name":"M. Fuertes","orcid":"https://orcid.org/0009-0001-1909-7397","observed_orcids":["https://orcid.org/0009-0001-1909-7397"]},"institutions":[{"id":"https://openalex.org/I149213910","display_name":"University of Antwerp","ror":"https://ror.org/008x57b05","country_code":"BE","type":"education","lineage":["https://openalex.org/I149213910"]}],"countries":["BE"],"is_corresponding":false,"raw_author_name":"Miguel de Diego Fuertes","raw_affiliation_strings":["Department of Family Medicine and Population Health, Global Health Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Family Medicine and Population Health, Global Health Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium","institution_ids":["https://openalex.org/I149213910"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5083832164","display_name":"Vincent Rennie","orcid":"https://orcid.org/0000-0002-1031-2441","observed_orcids":["https://orcid.org/0000-0002-1031-2441"]},"institutions":[{"id":"https://openalex.org/I149213910","display_name":"University of Antwerp","ror":"https://ror.org/008x57b05","country_code":"BE","type":"education","lineage":["https://openalex.org/I149213910"]}],"countries":["BE"],"is_corresponding":false,"raw_author_name":"Vincent Rennie","raw_affiliation_strings":["Department of Family Medicine and Population Health, Global Health Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Family Medicine and Population Health, Global Health Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium","institution_ids":["https://openalex.org/I149213910"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5046450198","display_name":"Emmanuel Rivi\u00e8re","orcid":"https://orcid.org/0000-0003-3410-218X","observed_orcids":["https://orcid.org/0000-0003-3410-218X"]},"institutions":[{"id":"https://openalex.org/I149213910","display_name":"University of Antwerp","ror":"https://ror.org/008x57b05","country_code":"BE","type":"education","lineage":["https://openalex.org/I149213910"]}],"countries":["BE"],"is_corresponding":false,"raw_author_name":"Emmanuel Riviere","raw_affiliation_strings":["Department of Family Medicine and Population Health, Global Health Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Family Medicine and Population Health, Global Health Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium","institution_ids":["https://openalex.org/I149213910"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110798845","display_name":"Mahdi Safarpour","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I149213910","display_name":"University of Antwerp","ror":"https://ror.org/008x57b05","country_code":"BE","type":"education","lineage":["https://openalex.org/I149213910"]}],"countries":["BE"],"is_corresponding":false,"raw_author_name":"Mahdi Safarpour","raw_affiliation_strings":["Department of Family Medicine and Population Health, Global Health Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Family Medicine and Population Health, Global Health Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium","institution_ids":["https://openalex.org/I149213910"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5053345229","display_name":"Annelies Van Rie","orcid":"https://orcid.org/0000-0001-7666-3263","observed_orcids":["https://orcid.org/0000-0001-7666-3263"]},"institutions":[{"id":"https://openalex.org/I149213910","display_name":"University of Antwerp","ror":"https://ror.org/008x57b05","country_code":"BE","type":"education","lineage":["https://openalex.org/I149213910"]}],"countries":["BE"],"is_corresponding":true,"raw_author_name":"Annelies Van Rie","raw_affiliation_strings":["Department of Family Medicine and Population Health, Global Health Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Family Medicine and Population Health, Global Health Institute, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium","institution_ids":["https://openalex.org/I149213910"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5053345229"],"corresponding_institution_ids":["https://openalex.org/I149213910"],"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/T10038","display_name":"Tuberculosis Research and Epidemiology","score":0.8910999894142151,"subfield":{"id":"https://openalex.org/subfields/2725","display_name":"Infectious Diseases"},"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/T10038","display_name":"Tuberculosis Research and Epidemiology","score":0.8910999894142151,"subfield":{"id":"https://openalex.org/subfields/2725","display_name":"Infectious Diseases"},"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/T10211","display_name":"Computational Drug Discovery Methods","score":0.021900000050663948,"subfield":{"id":"https://openalex.org/subfields/3002","display_name":"Drug Discovery"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10147","display_name":"Antibiotic Resistance in Bacteria","score":0.00930000003427267,"subfield":{"id":"https://openalex.org/subfields/2726","display_name":"Microbiology (medical)"},"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/bedaquiline-resistance","display_name":"bedaquiline resistance","score":0.9679999947547913},{"id":"https://openalex.org/keywords/mycobacterium-tuberculosis","display_name":"Mycobacterium tuberculosis","score":0.953000009059906},{"id":"https://openalex.org/keywords/rv0678","display_name":"Rv0678","score":0.9789999723434448},{"id":"https://openalex.org/keywords/missense-mutations","display_name":"missense mutations","score":0.9240000247955322},{"id":"https://openalex.org/keywords/in-silico-prediction","display_name":"in silico prediction","score":0.6340000033378601},{"id":"https://openalex.org/keywords/rifampicin-resistant-tuberculosis","display_name":"rifampicin-resistant tuberculosis","score":0.8090000152587891},{"id":"https://openalex.org/keywords/drug-resistance","display_name":"drug resistance","score":0.49799999594688416},{"id":"https://openalex.org/keywords/protein-structure","display_name":"protein structure","score":0.4359999895095825},{"id":"https://openalex.org/keywords/variant-interpretation","display_name":"variant interpretation","score":0.5239999890327454},{"id":"https://openalex.org/keywords/machine-learning","display_name":"machine learning","score":0.5270000100135803}],"concepts":[{"id":"https://openalex.org/C75563809","wikidata":"https://www.wikidata.org/wiki/Q2656896","display_name":"Missense mutation","level":4,"score":0.7876999974250793},{"id":"https://openalex.org/C2780544761","wikidata":"https://www.wikidata.org/wiki/Q1257318","display_name":"Bedaquiline","level":4,"score":0.7857000231742859},{"id":"https://openalex.org/C127716648","wikidata":"https://www.wikidata.org/wiki/Q104053","display_name":"Phenotype","level":3,"score":0.5902000069618225},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.49149999022483826},{"id":"https://openalex.org/C501734568","wikidata":"https://www.wikidata.org/wiki/Q42918","display_name":"Mutation","level":3,"score":0.41839998960494995},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.41119998693466187},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.37310001254081726},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.34619998931884766},{"id":"https://openalex.org/C163763905","wikidata":"https://www.wikidata.org/wiki/Q17075943","display_name":"Precision medicine","level":2,"score":0.34150001406669617},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.3353999853134155},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.3249000012874603},{"id":"https://openalex.org/C544519230","wikidata":"https://www.wikidata.org/wiki/Q32566","display_name":"Computed tomography","level":2,"score":0.2992999851703644},{"id":"https://openalex.org/C2779974597","wikidata":"https://www.wikidata.org/wiki/Q28448986","display_name":"Clinical Practice","level":2,"score":0.2806999981403351},{"id":"https://openalex.org/C3020646490","wikidata":"https://www.wikidata.org/wiki/Q25203551","display_name":"Clinical phenotype","level":4,"score":0.27799999713897705},{"id":"https://openalex.org/C100253034","wikidata":"https://www.wikidata.org/wiki/Q196372","display_name":"Systematic error","level":2,"score":0.2651999890804291},{"id":"https://openalex.org/C2984968299","wikidata":"https://www.wikidata.org/wiki/Q1077784","display_name":"Software tool","level":3,"score":0.2623000144958496},{"id":"https://openalex.org/C2777904410","wikidata":"https://www.wikidata.org/wiki/Q7397","display_name":"Software","level":2,"score":0.2522999942302704}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.02.12.705543","doi":"https://doi.org/10.64898/2026.02.12.705543","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.02.12.705543","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":"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:10.64898/2026.02.12.705543","doi":"https://doi.org/10.64898/2026.02.12.705543","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.02.12.705543","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":"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":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9391000270843506}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":21,"referenced_works":["https://openalex.org/W1591524996","https://openalex.org/W2005166795","https://openalex.org/W2044573154","https://openalex.org/W2103459989","https://openalex.org/W2143210482","https://openalex.org/W2376573086","https://openalex.org/W2560438049","https://openalex.org/W2945403072","https://openalex.org/W2947097964","https://openalex.org/W2952481429","https://openalex.org/W3035738663","https://openalex.org/W3098350347","https://openalex.org/W3198161252","https://openalex.org/W4309646522","https://openalex.org/W4313480451","https://openalex.org/W4361195623","https://openalex.org/W4390699263","https://openalex.org/W4393064349","https://openalex.org/W4410285291","https://openalex.org/W4412522825","https://openalex.org/W7155509363"],"related_works":["https://openalex.org/W4313480451","https://openalex.org/W4372347375","https://openalex.org/W4390725532","https://openalex.org/W4404241159","https://openalex.org/W2947097964","https://openalex.org/W2563852803","https://openalex.org/W4379599480","https://openalex.org/W4411413271","https://openalex.org/W4380627407","https://openalex.org/W4311697390"],"abstract_inverted_index":{"ABSTRACT":[0],"Bedaquiline":[1],"resistance":[2],"is":[3],"emerging":[4],"globally":[5],"and":[6,29,60,78,91,122,142],"threatens":[7],"the":[8,11,51,56,61,80,106,118,125,134,137],"effectiveness":[9],"of":[10,32,136,139,146],"novel":[12],"short":[13],"all-oral":[14],"regimens":[15],"for":[16],"rifampicin-resistant":[17,147],"tuberculosis.":[18,148],"Following":[19],"a":[20],"systematic":[21],"literature":[22],"review,":[23],"we":[24,48],"quantified":[25],"13":[26],"sequence,":[27],"biochemical,":[28],"structural":[30],"features":[31,54],"62":[33],"Rv0678":[34,140],"missense":[35,115],"variants":[36,116,141],"reported":[37],"in":[38,100,128],"136":[39],"Mycobacterium":[40],"tuberculosis":[41],"isolates.":[42],"Using":[43],"rigorous":[44],"machine":[45],"learning":[46],"methods,":[47],"show":[49],"that":[50],"strongest":[52],"contributing":[53],"were":[55],"evolutionary":[57],"conservation":[58],"score":[59],"shortest":[62],"atomic":[63],"distance":[64],"to":[65,105],"key":[66],"functional":[67],"sites.":[68],"The":[69],"final":[70],"5-feature":[71],"model":[72],"had":[73],"good":[74],"performance":[75],"(ROC-AUC":[76],"0.826)":[77],"classified":[79],"bedaquiline":[81],"phenotype":[82],"with":[83],"high":[84],"accuracy":[85],"[sensitivity":[86],"87.1%":[87],"(95%":[88,94],"CI,":[89,95],"78.3\u201392.6)":[90],"specificity":[92],"88.2%":[93],"76.6\u201394.5)].":[96],"Performance":[97],"was":[98],"lower":[99],"external":[101],"validation,":[102],"likely":[103],"due":[104],"measurement":[107],"error":[108],"introduced":[109],"when":[110],"using":[111],"diverse":[112],"phenotypic":[113],"methods.":[114],"on":[117],"mmpR5":[119],"protein":[120],"structure":[121],"function.":[123],"Integrating":[124],"five-feature":[126],"in-silico":[127],"variant":[129],"interpretation":[130],"software":[131],"could":[132],"improve":[133],"prediction":[135],"effect":[138],"guide":[143],"clinical":[144],"management":[145]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2026-02-15T00:00:00"}