Improving pharmacogenetic prediction of extrapyramidal symptoms induced by antipshycotics

In previous work we developed a pharmacogenetic predictor of antipsychotic (AP) induced extrapyramidal symptoms (EPS) based on four genes involved in mTOR regulation. The main objective is to improve this predictor by increasing its biological plausibility and replication. We re-sequence the four ge...

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Autores: Boloc, Daniel, Gortat, Anna, Cheng-Zhang, Jia Qi, García Cerro, Susana, Rodríguez Ferret, Natalia, Parellada, Mara, Saiz Ruiz, Jerónimo, Cuesta, Manuel J., Gassó Astorga, Patricia, Lafuente, Amàlia, 1952-2022, Bernardo Arroyo, Miquel, Mas Herrero, Sergi
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2018
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/156048
Acceso en línea:https://hdl.handle.net/2445/156048
Access Level:acceso abierto
Palabra clave:Farmacogenètica
Antipsicòtics
Pharmacogenetics
Antipsychotic drugs
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spelling Improving pharmacogenetic prediction of extrapyramidal symptoms induced by antipshycoticsBoloc, DanielGortat, AnnaCheng-Zhang, Jia QiGarcía Cerro, SusanaRodríguez Ferret, NataliaParellada, MaraSaiz Ruiz, JerónimoCuesta, Manuel J.Gassó Astorga, PatriciaLafuente, Amàlia, 1952-2022Bernardo Arroyo, MiquelMas Herrero, SergiFarmacogenèticaAntipsicòticsPharmacogeneticsAntipsychotic drugsIn previous work we developed a pharmacogenetic predictor of antipsychotic (AP) induced extrapyramidal symptoms (EPS) based on four genes involved in mTOR regulation. The main objective is to improve this predictor by increasing its biological plausibility and replication. We re-sequence the four genes using next-generation sequencing. We predict functionality 'in silico' of all identified SNPs and test it using gene reporter assays. Using functional SNPs, we develop a new predictor utilizing machine learning algorithms (Discovery Cohort, N = 131) and replicate it in two independent cohorts (Replication Cohort 1, N = 113; Replication Cohort 2, N = 113). After prioritization, four SNPs were used to develop the pharmacogenetic predictor of AP-induced EPS. The model constructed using the Naive Bayes algorithm achieved a 66% of accuracy in the Discovery Cohort, and similar performances in the replication cohorts. The result is an improved pharmacogenetic predictor of AP-induced EPS, which is more robust and generalizable than the original.Nature Publishing Group2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/156048Articles publicats en revistes (Fonaments Clínics)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/s41398-018-0330-4Translational Psychiatry, 2018, vol. 8, num. 1, p. 276https://doi.org/10.1038/s41398-018-0330-4cc-by-nc-nd (c) Boloc, Daniel et al., 2018http://creativecommons.org/licenses/by-nc-nd/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1560482026-05-27T06:46:51Z
dc.title.none.fl_str_mv Improving pharmacogenetic prediction of extrapyramidal symptoms induced by antipshycotics
title Improving pharmacogenetic prediction of extrapyramidal symptoms induced by antipshycotics
spellingShingle Improving pharmacogenetic prediction of extrapyramidal symptoms induced by antipshycotics
Boloc, Daniel
Farmacogenètica
Antipsicòtics
Pharmacogenetics
Antipsychotic drugs
title_short Improving pharmacogenetic prediction of extrapyramidal symptoms induced by antipshycotics
title_full Improving pharmacogenetic prediction of extrapyramidal symptoms induced by antipshycotics
title_fullStr Improving pharmacogenetic prediction of extrapyramidal symptoms induced by antipshycotics
title_full_unstemmed Improving pharmacogenetic prediction of extrapyramidal symptoms induced by antipshycotics
title_sort Improving pharmacogenetic prediction of extrapyramidal symptoms induced by antipshycotics
dc.creator.none.fl_str_mv Boloc, Daniel
Gortat, Anna
Cheng-Zhang, Jia Qi
García Cerro, Susana
Rodríguez Ferret, Natalia
Parellada, Mara
Saiz Ruiz, Jerónimo
Cuesta, Manuel J.
Gassó Astorga, Patricia
Lafuente, Amàlia, 1952-2022
Bernardo Arroyo, Miquel
Mas Herrero, Sergi
author Boloc, Daniel
author_facet Boloc, Daniel
Gortat, Anna
Cheng-Zhang, Jia Qi
García Cerro, Susana
Rodríguez Ferret, Natalia
Parellada, Mara
Saiz Ruiz, Jerónimo
Cuesta, Manuel J.
Gassó Astorga, Patricia
Lafuente, Amàlia, 1952-2022
Bernardo Arroyo, Miquel
Mas Herrero, Sergi
author_role author
author2 Gortat, Anna
Cheng-Zhang, Jia Qi
García Cerro, Susana
Rodríguez Ferret, Natalia
Parellada, Mara
Saiz Ruiz, Jerónimo
Cuesta, Manuel J.
Gassó Astorga, Patricia
Lafuente, Amàlia, 1952-2022
Bernardo Arroyo, Miquel
Mas Herrero, Sergi
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Farmacogenètica
Antipsicòtics
Pharmacogenetics
Antipsychotic drugs
topic Farmacogenètica
Antipsicòtics
Pharmacogenetics
Antipsychotic drugs
description In previous work we developed a pharmacogenetic predictor of antipsychotic (AP) induced extrapyramidal symptoms (EPS) based on four genes involved in mTOR regulation. The main objective is to improve this predictor by increasing its biological plausibility and replication. We re-sequence the four genes using next-generation sequencing. We predict functionality 'in silico' of all identified SNPs and test it using gene reporter assays. Using functional SNPs, we develop a new predictor utilizing machine learning algorithms (Discovery Cohort, N = 131) and replicate it in two independent cohorts (Replication Cohort 1, N = 113; Replication Cohort 2, N = 113). After prioritization, four SNPs were used to develop the pharmacogenetic predictor of AP-induced EPS. The model constructed using the Naive Bayes algorithm achieved a 66% of accuracy in the Discovery Cohort, and similar performances in the replication cohorts. The result is an improved pharmacogenetic predictor of AP-induced EPS, which is more robust and generalizable than the original.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/156048
url https://hdl.handle.net/2445/156048
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/s41398-018-0330-4
Translational Psychiatry, 2018, vol. 8, num. 1, p. 276
https://doi.org/10.1038/s41398-018-0330-4
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Boloc, Daniel et al., 2018
http://creativecommons.org/licenses/by-nc-nd/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Boloc, Daniel et al., 2018
http://creativecommons.org/licenses/by-nc-nd/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv Articles publicats en revistes (Fonaments Clínics)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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