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Title: Improving pharmacogenetic prediction of extrapyramidal symptoms induced by antipshycotics
Author: Boloc, Daniel
Gortat, Anna
Cheng-Zhang, Jia Qi
García-Cerro, Susana
Rodríguez Ferret, Natalia
Parellada, Mara
Saiz Ruiz, Jerónimo
Cuesta, Manolo J.
Gassó Astorga, Patricia
Lafuente, Amàlia, 1952-
Bernardo Arroyo, Miquel
Mas Herrero, Sergi
Keywords: Farmacogenètica
Antipsychotic drugs
Issue Date: 13-Dec-2018
Publisher: Nature Publishing Group
Abstract: 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.
Note: Reproducció del document publicat a:
It is part of: Translational Psychiatry, 2018, vol. 8, num. 1, p. 276
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ISSN: 2158-3188
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Fonaments Clínics)
Articles publicats en revistes (Medicina)

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