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Combining Clinical and Genetic Data to Predict Response to Fingolimod Treatment in Relapsing Remitting Multiple Sclerosis Patients: A Precision Medicine Approach
A personalized approach is strongly advocated for treatment selection in Multiple Sclerosis patients due to the high number of available drugs. Machine learning methods proved to be valuable tools in the context of precision medicine. In the present work, we applied machine learning methods to ident...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9861774/ https://www.ncbi.nlm.nih.gov/pubmed/36675783 http://dx.doi.org/10.3390/jpm13010122 |
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author | Ferrè, Laura Clarelli, Ferdinando Pignolet, Beatrice Mascia, Elisabetta Frasca, Marco Santoro, Silvia Sorosina, Melissa Bucciarelli, Florence Moiola, Lucia Martinelli, Vittorio Comi, Giancarlo Liblau, Roland Filippi, Massimo Valentini, Giorgio Esposito, Federica |
author_facet | Ferrè, Laura Clarelli, Ferdinando Pignolet, Beatrice Mascia, Elisabetta Frasca, Marco Santoro, Silvia Sorosina, Melissa Bucciarelli, Florence Moiola, Lucia Martinelli, Vittorio Comi, Giancarlo Liblau, Roland Filippi, Massimo Valentini, Giorgio Esposito, Federica |
author_sort | Ferrè, Laura |
collection | PubMed |
description | A personalized approach is strongly advocated for treatment selection in Multiple Sclerosis patients due to the high number of available drugs. Machine learning methods proved to be valuable tools in the context of precision medicine. In the present work, we applied machine learning methods to identify a combined clinical and genetic signature of response to fingolimod that could support the prediction of drug response. Two cohorts of fingolimod-treated patients from Italy and France were enrolled and divided into training, validation, and test set. Random forest training and robust feature selection were performed in the first two sets respectively, and the independent test set was used to evaluate model performance. A genetic-only model and a combined clinical–genetic model were obtained. Overall, 381 patients were classified according to the NEDA-3 criterion at 2 years; we identified a genetic model, including 123 SNPs, that was able to predict fingolimod response with an AUROC= 0.65 in the independent test set. When combining clinical data, the model accuracy increased to an AUROC= 0.71. Integrating clinical and genetic data by means of machine learning methods can help in the prediction of response to fingolimod, even though further studies are required to definitely extend this approach to clinical applications |
format | Online Article Text |
id | pubmed-9861774 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-98617742023-01-22 Combining Clinical and Genetic Data to Predict Response to Fingolimod Treatment in Relapsing Remitting Multiple Sclerosis Patients: A Precision Medicine Approach Ferrè, Laura Clarelli, Ferdinando Pignolet, Beatrice Mascia, Elisabetta Frasca, Marco Santoro, Silvia Sorosina, Melissa Bucciarelli, Florence Moiola, Lucia Martinelli, Vittorio Comi, Giancarlo Liblau, Roland Filippi, Massimo Valentini, Giorgio Esposito, Federica J Pers Med Article A personalized approach is strongly advocated for treatment selection in Multiple Sclerosis patients due to the high number of available drugs. Machine learning methods proved to be valuable tools in the context of precision medicine. In the present work, we applied machine learning methods to identify a combined clinical and genetic signature of response to fingolimod that could support the prediction of drug response. Two cohorts of fingolimod-treated patients from Italy and France were enrolled and divided into training, validation, and test set. Random forest training and robust feature selection were performed in the first two sets respectively, and the independent test set was used to evaluate model performance. A genetic-only model and a combined clinical–genetic model were obtained. Overall, 381 patients were classified according to the NEDA-3 criterion at 2 years; we identified a genetic model, including 123 SNPs, that was able to predict fingolimod response with an AUROC= 0.65 in the independent test set. When combining clinical data, the model accuracy increased to an AUROC= 0.71. Integrating clinical and genetic data by means of machine learning methods can help in the prediction of response to fingolimod, even though further studies are required to definitely extend this approach to clinical applications MDPI 2023-01-06 /pmc/articles/PMC9861774/ /pubmed/36675783 http://dx.doi.org/10.3390/jpm13010122 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ferrè, Laura Clarelli, Ferdinando Pignolet, Beatrice Mascia, Elisabetta Frasca, Marco Santoro, Silvia Sorosina, Melissa Bucciarelli, Florence Moiola, Lucia Martinelli, Vittorio Comi, Giancarlo Liblau, Roland Filippi, Massimo Valentini, Giorgio Esposito, Federica Combining Clinical and Genetic Data to Predict Response to Fingolimod Treatment in Relapsing Remitting Multiple Sclerosis Patients: A Precision Medicine Approach |
title | Combining Clinical and Genetic Data to Predict Response to Fingolimod Treatment in Relapsing Remitting Multiple Sclerosis Patients: A Precision Medicine Approach |
title_full | Combining Clinical and Genetic Data to Predict Response to Fingolimod Treatment in Relapsing Remitting Multiple Sclerosis Patients: A Precision Medicine Approach |
title_fullStr | Combining Clinical and Genetic Data to Predict Response to Fingolimod Treatment in Relapsing Remitting Multiple Sclerosis Patients: A Precision Medicine Approach |
title_full_unstemmed | Combining Clinical and Genetic Data to Predict Response to Fingolimod Treatment in Relapsing Remitting Multiple Sclerosis Patients: A Precision Medicine Approach |
title_short | Combining Clinical and Genetic Data to Predict Response to Fingolimod Treatment in Relapsing Remitting Multiple Sclerosis Patients: A Precision Medicine Approach |
title_sort | combining clinical and genetic data to predict response to fingolimod treatment in relapsing remitting multiple sclerosis patients: a precision medicine approach |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9861774/ https://www.ncbi.nlm.nih.gov/pubmed/36675783 http://dx.doi.org/10.3390/jpm13010122 |
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