A molecular barcode and web-based data analysis tool to identify imported Plasmodium vivax malaria

ABSTRACT: Traditionally, patient travel history has been used to distinguish imported from autochthonous malaria cases, but the dormant liver stages of Plasmodium vivax confound this approach. Molecular tools offer an alternative method to identify, and map imported cases. Using machine learning app...

Full description

Autores:
Lopera Mesa, Tatiana María
Tobón Castaño, Alberto
Vélez Beranal, Iván Darío
Montenegro Cadena, Lidia Madeline
Assefa, Ashenafi
Aseffa, Abraham
Auburn, Sarah
Barry, Alyssa
Batista Pereira, Dhelio B.
Barber, Bridget
Chau, Nguyen H.
Chu, Cindy S.
Drury, Eleanor
Echeverry, Diego F.
Espino, Fe E. J.
Ferreira, Marcelo U.
Gao, Qi
Getachew, Sisay
Gonçalves, Sónia
Green, Justin A.
Grigg, Matthew J.
Hamedi, Yaghoob
Hiền, Trần T
Khan, Wasif A.
Koh, Gavin
Krudsood, Srivicha
Kwiatkowski, Dominic P.
Lacerda, Marcus V. G.
Laman, Moses
Ley, Benedikt
Liu, Yaobao
Llanos Cuentas, Alejandro
Lon, Chanthap
Adam, Ishag
Marfurt, Jutta
Miles, Alistair
Miotto, Olivo
Mohammed, Rezika
Anstey, Nicholas M.
Mueller, Ivo
Namaik Larp, Chayadol
Noviyanti, Rintis
Nosten, Francois
Pava, Zuleima
Pearson, Richard D.
Petros, Beyene
Price, Ric N.
Rahim, Awab G.
Rayner, Julian C.
Simpson, Victoria
Sriprawat, Kanlaya
Sutanto, Edwin
Thriemer, Kamala
Alam, Mohammad S.
Trimarsanto, Hidayat
Villegas, María F.
Amato, Roberto
Wangchuck, Sonam
White, Nicholas J.
William, Timothy
Yilma, Daniel
Tipo de recurso:
Article of investigation
Fecha de publicación:
2022
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
eng
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/41496
Acceso en línea:
https://hdl.handle.net/10495/41496
Palabra clave:
Funciones de Verosimilitud
Likelihood Functions
Malaria
Plasmodium vivax
Malaria Vivax
Código de Barras del ADN Taxonómico
DNA Barcoding, Taxonomic
Análisis de Datos
Data Analysis
https://id.nlm.nih.gov/mesh/D058893
https://id.nlm.nih.gov/mesh/D016013
https://id.nlm.nih.gov/mesh/D008288
https://id.nlm.nih.gov/mesh/D010966
https://id.nlm.nih.gov/mesh/D016780
https://id.nlm.nih.gov/mesh/D000078332
Rights
openAccess
License
http://creativecommons.org/licenses/by/2.5/co/
id UDEA2_21323ca18f0b2756b9f71915dd5783ad
oai_identifier_str oai:bibliotecadigital.udea.edu.co:10495/41496
network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.spa.fl_str_mv A molecular barcode and web-based data analysis tool to identify imported Plasmodium vivax malaria
title A molecular barcode and web-based data analysis tool to identify imported Plasmodium vivax malaria
spellingShingle A molecular barcode and web-based data analysis tool to identify imported Plasmodium vivax malaria
Funciones de Verosimilitud
Likelihood Functions
Malaria
Plasmodium vivax
Malaria Vivax
Código de Barras del ADN Taxonómico
DNA Barcoding, Taxonomic
Análisis de Datos
Data Analysis
https://id.nlm.nih.gov/mesh/D058893
https://id.nlm.nih.gov/mesh/D016013
https://id.nlm.nih.gov/mesh/D008288
https://id.nlm.nih.gov/mesh/D010966
https://id.nlm.nih.gov/mesh/D016780
https://id.nlm.nih.gov/mesh/D000078332
title_short A molecular barcode and web-based data analysis tool to identify imported Plasmodium vivax malaria
title_full A molecular barcode and web-based data analysis tool to identify imported Plasmodium vivax malaria
title_fullStr A molecular barcode and web-based data analysis tool to identify imported Plasmodium vivax malaria
title_full_unstemmed A molecular barcode and web-based data analysis tool to identify imported Plasmodium vivax malaria
title_sort A molecular barcode and web-based data analysis tool to identify imported Plasmodium vivax malaria
dc.creator.fl_str_mv Lopera Mesa, Tatiana María
Tobón Castaño, Alberto
Vélez Beranal, Iván Darío
Montenegro Cadena, Lidia Madeline
Assefa, Ashenafi
Aseffa, Abraham
Auburn, Sarah
Barry, Alyssa
Batista Pereira, Dhelio B.
Barber, Bridget
Chau, Nguyen H.
Chu, Cindy S.
Drury, Eleanor
Echeverry, Diego F.
Espino, Fe E. J.
Ferreira, Marcelo U.
Gao, Qi
Getachew, Sisay
Gonçalves, Sónia
Green, Justin A.
Grigg, Matthew J.
Hamedi, Yaghoob
Hiền, Trần T
Khan, Wasif A.
Koh, Gavin
Krudsood, Srivicha
Kwiatkowski, Dominic P.
Lacerda, Marcus V. G.
Laman, Moses
Ley, Benedikt
Liu, Yaobao
Llanos Cuentas, Alejandro
Lon, Chanthap
Adam, Ishag
Marfurt, Jutta
Miles, Alistair
Miotto, Olivo
Mohammed, Rezika
Anstey, Nicholas M.
Mueller, Ivo
Namaik Larp, Chayadol
Noviyanti, Rintis
Nosten, Francois
Pava, Zuleima
Pearson, Richard D.
Petros, Beyene
Price, Ric N.
Rahim, Awab G.
Rayner, Julian C.
Simpson, Victoria
Sriprawat, Kanlaya
Sutanto, Edwin
Thriemer, Kamala
Alam, Mohammad S.
Trimarsanto, Hidayat
Villegas, María F.
Amato, Roberto
Wangchuck, Sonam
White, Nicholas J.
William, Timothy
Yilma, Daniel
dc.contributor.author.none.fl_str_mv Lopera Mesa, Tatiana María
Tobón Castaño, Alberto
Vélez Beranal, Iván Darío
Montenegro Cadena, Lidia Madeline
Assefa, Ashenafi
Aseffa, Abraham
Auburn, Sarah
Barry, Alyssa
Batista Pereira, Dhelio B.
Barber, Bridget
Chau, Nguyen H.
Chu, Cindy S.
Drury, Eleanor
Echeverry, Diego F.
Espino, Fe E. J.
Ferreira, Marcelo U.
Gao, Qi
Getachew, Sisay
Gonçalves, Sónia
Green, Justin A.
Grigg, Matthew J.
Hamedi, Yaghoob
Hiền, Trần T
Khan, Wasif A.
Koh, Gavin
Krudsood, Srivicha
Kwiatkowski, Dominic P.
Lacerda, Marcus V. G.
Laman, Moses
Ley, Benedikt
Liu, Yaobao
Llanos Cuentas, Alejandro
Lon, Chanthap
Adam, Ishag
Marfurt, Jutta
Miles, Alistair
Miotto, Olivo
Mohammed, Rezika
Anstey, Nicholas M.
Mueller, Ivo
Namaik Larp, Chayadol
Noviyanti, Rintis
Nosten, Francois
Pava, Zuleima
Pearson, Richard D.
Petros, Beyene
Price, Ric N.
Rahim, Awab G.
Rayner, Julian C.
Simpson, Victoria
Sriprawat, Kanlaya
Sutanto, Edwin
Thriemer, Kamala
Alam, Mohammad S.
Trimarsanto, Hidayat
Villegas, María F.
Amato, Roberto
Wangchuck, Sonam
White, Nicholas J.
William, Timothy
Yilma, Daniel
dc.contributor.researchgroup.spa.fl_str_mv Grupo Malaria
Programa de Estudio y Control de Enfermedades Tropicales (PECET)
dc.subject.decs.none.fl_str_mv Funciones de Verosimilitud
Likelihood Functions
Malaria
Plasmodium vivax
Malaria Vivax
Código de Barras del ADN Taxonómico
DNA Barcoding, Taxonomic
Análisis de Datos
Data Analysis
topic Funciones de Verosimilitud
Likelihood Functions
Malaria
Plasmodium vivax
Malaria Vivax
Código de Barras del ADN Taxonómico
DNA Barcoding, Taxonomic
Análisis de Datos
Data Analysis
https://id.nlm.nih.gov/mesh/D058893
https://id.nlm.nih.gov/mesh/D016013
https://id.nlm.nih.gov/mesh/D008288
https://id.nlm.nih.gov/mesh/D010966
https://id.nlm.nih.gov/mesh/D016780
https://id.nlm.nih.gov/mesh/D000078332
dc.subject.meshuri.none.fl_str_mv https://id.nlm.nih.gov/mesh/D058893
https://id.nlm.nih.gov/mesh/D016013
https://id.nlm.nih.gov/mesh/D008288
https://id.nlm.nih.gov/mesh/D010966
https://id.nlm.nih.gov/mesh/D016780
https://id.nlm.nih.gov/mesh/D000078332
description ABSTRACT: Traditionally, patient travel history has been used to distinguish imported from autochthonous malaria cases, but the dormant liver stages of Plasmodium vivax confound this approach. Molecular tools offer an alternative method to identify, and map imported cases. Using machine learning approaches incorporating hierarchical fixation index and decision tree analyses applied to 799 P. vivax genomes from 21 countries, we identified 33-SNP, 50-SNP and 55-SNP barcodes (GEO33, GEO50 and GEO55), with high capacity to predict the infection's country of origin. The Matthews correlation coefficient (MCC) for an existing, commonly applied 38-SNP barcode (BR38) exceeded 0.80 in 62% countries. The GEO panels outperformed BR38, with median MCCs > 0.80 in 90% countries at GEO33, and 95% at GEO50 and GEO55. An online, open-access, likelihood-based classifier framework was established to support data analysis (vivaxGEN-geo). The SNP selection and classifier methods can be readily amended for other use cases to support malaria control program
publishDate 2022
dc.date.issued.none.fl_str_mv 2022
dc.date.accessioned.none.fl_str_mv 2024-08-26T23:36:01Z
dc.date.available.none.fl_str_mv 2024-08-26T23:36:01Z
dc.type.spa.fl_str_mv Artículo de investigación
dc.type.coar.spa.fl_str_mv http://purl.org/coar/resource_type/c_2df8fbb1
dc.type.redcol.spa.fl_str_mv https://purl.org/redcol/resource_type/ART
dc.type.coarversion.spa.fl_str_mv http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.driver.spa.fl_str_mv info:eu-repo/semantics/article
dc.type.version.spa.fl_str_mv info:eu-repo/semantics/publishedVersion
format http://purl.org/coar/resource_type/c_2df8fbb1
status_str publishedVersion
dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10495/41496
dc.identifier.doi.none.fl_str_mv 10.1038/s42003-022-04352-2
dc.identifier.eissn.none.fl_str_mv 2399-3642
url https://hdl.handle.net/10495/41496
identifier_str_mv 10.1038/s42003-022-04352-2
2399-3642
dc.language.iso.spa.fl_str_mv eng
language eng
dc.relation.ispartofjournalabbrev.spa.fl_str_mv Commun. Biol.
dc.relation.citationendpage.spa.fl_str_mv 10
dc.relation.citationissue.spa.fl_str_mv 1
dc.relation.citationstartpage.spa.fl_str_mv 1
dc.relation.citationvolume.spa.fl_str_mv 5
dc.relation.ispartofjournal.spa.fl_str_mv Communications Biology
dc.rights.uri.*.fl_str_mv http://creativecommons.org/licenses/by/2.5/co/
dc.rights.uri.spa.fl_str_mv https://creativecommons.org/licenses/by/4.0/
dc.rights.accessrights.spa.fl_str_mv info:eu-repo/semantics/openAccess
dc.rights.coar.spa.fl_str_mv http://purl.org/coar/access_right/c_abf2
rights_invalid_str_mv http://creativecommons.org/licenses/by/2.5/co/
https://creativecommons.org/licenses/by/4.0/
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.extent.spa.fl_str_mv 10 páginas
dc.format.mimetype.spa.fl_str_mv application/pdf
dc.publisher.spa.fl_str_mv Nature Publishing Group UK
dc.publisher.place.spa.fl_str_mv Londres, Inglaterra
institution Universidad de Antioquia
bitstream.url.fl_str_mv https://bibliotecadigital.udea.edu.co/bitstreams/5220a0d1-9d22-44b0-a51b-89240f34e4a5/download
https://bibliotecadigital.udea.edu.co/bitstreams/c720f5c8-1652-4543-b718-00751454b7e2/download
https://bibliotecadigital.udea.edu.co/bitstreams/80ef6e7f-8976-4f7e-a488-cdc20666575c/download
https://bibliotecadigital.udea.edu.co/bitstreams/079ab426-b4d8-4a9a-8e90-14970c93cc63/download
https://bibliotecadigital.udea.edu.co/bitstreams/e9f3409e-7f61-4bd4-8433-a18f8dd1673b/download
bitstream.checksum.fl_str_mv 1646d1f6b96dbbbc38035efc9239ac9c
8a4605be74aa9ea9d79846c1fba20a33
70f2e318bae1dec28730c5dc7b9a9ceb
4e2f696568efbd3d666d6a7dc7a2b86b
674fc1e14cdc1fdc7016f753ba8574ac
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositorio Institucional de la Universidad de Antioquia
repository.mail.fl_str_mv aplicacionbibliotecadigitalbiblioteca@udea.edu.co
_version_ 1851052135877181440
spelling Lopera Mesa, Tatiana MaríaTobón Castaño, AlbertoVélez Beranal, Iván DaríoMontenegro Cadena, Lidia MadelineAssefa, AshenafiAseffa, AbrahamAuburn, SarahBarry, AlyssaBatista Pereira, Dhelio B.Barber, BridgetChau, Nguyen H.Chu, Cindy S.Drury, EleanorEcheverry, Diego F.Espino, Fe E. J.Ferreira, Marcelo U.Gao, QiGetachew, SisayGonçalves, SóniaGreen, Justin A.Grigg, Matthew J.Hamedi, YaghoobHiền, Trần TKhan, Wasif A.Koh, GavinKrudsood, SrivichaKwiatkowski, Dominic P.Lacerda, Marcus V. G.Laman, MosesLey, BenediktLiu, YaobaoLlanos Cuentas, AlejandroLon, ChanthapAdam, IshagMarfurt, JuttaMiles, AlistairMiotto, OlivoMohammed, RezikaAnstey, Nicholas M.Mueller, IvoNamaik Larp, ChayadolNoviyanti, RintisNosten, FrancoisPava, ZuleimaPearson, Richard D.Petros, BeyenePrice, Ric N.Rahim, Awab G.Rayner, Julian C.Simpson, VictoriaSriprawat, KanlayaSutanto, EdwinThriemer, KamalaAlam, Mohammad S.Trimarsanto, HidayatVillegas, María F.Amato, RobertoWangchuck, SonamWhite, Nicholas J.William, TimothyYilma, DanielGrupo MalariaPrograma de Estudio y Control de Enfermedades Tropicales (PECET)2024-08-26T23:36:01Z2024-08-26T23:36:01Z2022https://hdl.handle.net/10495/4149610.1038/s42003-022-04352-22399-3642ABSTRACT: Traditionally, patient travel history has been used to distinguish imported from autochthonous malaria cases, but the dormant liver stages of Plasmodium vivax confound this approach. Molecular tools offer an alternative method to identify, and map imported cases. Using machine learning approaches incorporating hierarchical fixation index and decision tree analyses applied to 799 P. vivax genomes from 21 countries, we identified 33-SNP, 50-SNP and 55-SNP barcodes (GEO33, GEO50 and GEO55), with high capacity to predict the infection's country of origin. The Matthews correlation coefficient (MCC) for an existing, commonly applied 38-SNP barcode (BR38) exceeded 0.80 in 62% countries. The GEO panels outperformed BR38, with median MCCs > 0.80 in 90% countries at GEO33, and 95% at GEO50 and GEO55. An online, open-access, likelihood-based classifier framework was established to support data analysis (vivaxGEN-geo). The SNP selection and classifier methods can be readily amended for other use cases to support malaria control programWellcome TrustMedical Research CouncilCOL0007524COL001509910 páginasapplication/pdfengNature Publishing Group UKLondres, Inglaterrahttp://creativecommons.org/licenses/by/2.5/co/https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2A molecular barcode and web-based data analysis tool to identify imported Plasmodium vivax malariaArtículo de investigaciónhttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARThttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionFunciones de VerosimilitudLikelihood FunctionsMalariaPlasmodium vivaxMalaria VivaxCódigo de Barras del ADN TaxonómicoDNA Barcoding, TaxonomicAnálisis de DatosData Analysishttps://id.nlm.nih.gov/mesh/D058893https://id.nlm.nih.gov/mesh/D016013https://id.nlm.nih.gov/mesh/D008288https://id.nlm.nih.gov/mesh/D010966https://id.nlm.nih.gov/mesh/D016780https://id.nlm.nih.gov/mesh/D000078332Commun. Biol.10115Communications Biology200909, 204911, 206194M006212RoR:029chgv08RoR:03x94j517PublicationCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-8927https://bibliotecadigital.udea.edu.co/bitstreams/5220a0d1-9d22-44b0-a51b-89240f34e4a5/download1646d1f6b96dbbbc38035efc9239ac9cMD52falseAnonymousREADLICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://bibliotecadigital.udea.edu.co/bitstreams/c720f5c8-1652-4543-b718-00751454b7e2/download8a4605be74aa9ea9d79846c1fba20a33MD53falseAnonymousREADORIGINALLoperaTatiana_2022_Molecular_Data_Plasmodium.pdfLoperaTatiana_2022_Molecular_Data_Plasmodium.pdfArtículo de investigaciónapplication/pdf2156053https://bibliotecadigital.udea.edu.co/bitstreams/80ef6e7f-8976-4f7e-a488-cdc20666575c/download70f2e318bae1dec28730c5dc7b9a9cebMD51trueAnonymousREADTEXTLoperaTatiana_2022_Molecular_Data_Plasmodium.pdf.txtLoperaTatiana_2022_Molecular_Data_Plasmodium.pdf.txtExtracted texttext/plain66545https://bibliotecadigital.udea.edu.co/bitstreams/079ab426-b4d8-4a9a-8e90-14970c93cc63/download4e2f696568efbd3d666d6a7dc7a2b86bMD56falseAnonymousREADTHUMBNAILLoperaTatiana_2022_Molecular_Data_Plasmodium.pdf.jpgLoperaTatiana_2022_Molecular_Data_Plasmodium.pdf.jpgGenerated Thumbnailimage/jpeg14151https://bibliotecadigital.udea.edu.co/bitstreams/e9f3409e-7f61-4bd4-8433-a18f8dd1673b/download674fc1e14cdc1fdc7016f753ba8574acMD57falseAnonymousREAD10495/41496oai:bibliotecadigital.udea.edu.co:10495/414962025-03-26 17:30:59.184http://creativecommons.org/licenses/by/2.5/co/open.accesshttps://bibliotecadigital.udea.edu.coRepositorio Institucional de la Universidad de Antioquiaaplicacionbibliotecadigitalbiblioteca@udea.edu.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