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Predictive modeling of antibiotic eradication therapy success for new-onset Pseudomonas aeruginosa pulmonary infections in children with cystic fibrosis
Chronic Pseudomonas aeruginosa (Pa) lung infections are the leading cause of mortality among cystic fibrosis (CF) patients; therefore, the eradication of new-onset Pa lung infections is an important therapeutic goal that can have long-term health benefits. The use of early antibiotic eradication the...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10506723/ https://www.ncbi.nlm.nih.gov/pubmed/37672526 http://dx.doi.org/10.1371/journal.pcbi.1011424 |
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author | Graña-Miraglia, Lucía Morales-Lizcano, Nadia Wang, Pauline W. Hwang, David M. Yau, Yvonne C. W. Waters, Valerie J. Guttman, David S. |
author_facet | Graña-Miraglia, Lucía Morales-Lizcano, Nadia Wang, Pauline W. Hwang, David M. Yau, Yvonne C. W. Waters, Valerie J. Guttman, David S. |
author_sort | Graña-Miraglia, Lucía |
collection | PubMed |
description | Chronic Pseudomonas aeruginosa (Pa) lung infections are the leading cause of mortality among cystic fibrosis (CF) patients; therefore, the eradication of new-onset Pa lung infections is an important therapeutic goal that can have long-term health benefits. The use of early antibiotic eradication therapy (AET) has been shown to clear the majority of new-onset Pa infections, and it is hoped that identifying the underlying basis for AET failure will further improve treatment outcomes. Here we generated machine learning models to predict AET outcomes based on pathogen genomic data. We used a nested cross validation design, population structure control, and recursive feature selection to improve model performance and showed that incorporating population structure control was crucial for improving model interpretation and generalizability. Our best model, controlling for population structure and using only 30 recursively selected features, had an area under the curve of 0.87 for a holdout test dataset. The top-ranked features were generally associated with motility, adhesion, and biofilm formation. |
format | Online Article Text |
id | pubmed-10506723 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-105067232023-09-19 Predictive modeling of antibiotic eradication therapy success for new-onset Pseudomonas aeruginosa pulmonary infections in children with cystic fibrosis Graña-Miraglia, Lucía Morales-Lizcano, Nadia Wang, Pauline W. Hwang, David M. Yau, Yvonne C. W. Waters, Valerie J. Guttman, David S. PLoS Comput Biol Research Article Chronic Pseudomonas aeruginosa (Pa) lung infections are the leading cause of mortality among cystic fibrosis (CF) patients; therefore, the eradication of new-onset Pa lung infections is an important therapeutic goal that can have long-term health benefits. The use of early antibiotic eradication therapy (AET) has been shown to clear the majority of new-onset Pa infections, and it is hoped that identifying the underlying basis for AET failure will further improve treatment outcomes. Here we generated machine learning models to predict AET outcomes based on pathogen genomic data. We used a nested cross validation design, population structure control, and recursive feature selection to improve model performance and showed that incorporating population structure control was crucial for improving model interpretation and generalizability. Our best model, controlling for population structure and using only 30 recursively selected features, had an area under the curve of 0.87 for a holdout test dataset. The top-ranked features were generally associated with motility, adhesion, and biofilm formation. Public Library of Science 2023-09-06 /pmc/articles/PMC10506723/ /pubmed/37672526 http://dx.doi.org/10.1371/journal.pcbi.1011424 Text en © 2023 Graña-Miraglia et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Graña-Miraglia, Lucía Morales-Lizcano, Nadia Wang, Pauline W. Hwang, David M. Yau, Yvonne C. W. Waters, Valerie J. Guttman, David S. Predictive modeling of antibiotic eradication therapy success for new-onset Pseudomonas aeruginosa pulmonary infections in children with cystic fibrosis |
title | Predictive modeling of antibiotic eradication therapy success for new-onset Pseudomonas aeruginosa pulmonary infections in children with cystic fibrosis |
title_full | Predictive modeling of antibiotic eradication therapy success for new-onset Pseudomonas aeruginosa pulmonary infections in children with cystic fibrosis |
title_fullStr | Predictive modeling of antibiotic eradication therapy success for new-onset Pseudomonas aeruginosa pulmonary infections in children with cystic fibrosis |
title_full_unstemmed | Predictive modeling of antibiotic eradication therapy success for new-onset Pseudomonas aeruginosa pulmonary infections in children with cystic fibrosis |
title_short | Predictive modeling of antibiotic eradication therapy success for new-onset Pseudomonas aeruginosa pulmonary infections in children with cystic fibrosis |
title_sort | predictive modeling of antibiotic eradication therapy success for new-onset pseudomonas aeruginosa pulmonary infections in children with cystic fibrosis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10506723/ https://www.ncbi.nlm.nih.gov/pubmed/37672526 http://dx.doi.org/10.1371/journal.pcbi.1011424 |
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